The Vicious Cycle of Obesity and Low Back Pain: A Comprehensive Review

Abstract

Obesity and low back pain (LBP) are major contributors to global disability and healthcare burden in both adults and children. Although a growing body of research supports a bidirectional relationship between these conditions, the underlying mechanisms remain poorly integrated in the current literature. While mechanical overload has traditionally been viewed as the principal link, emerging evidence points to additional roles for metabolic dysregulation, chronic low-grade inflammation, and adipokine activity in the development and persistence of LBP. This review addresses the need for a comprehensive synthesis of how obesity affects spinal structures, including the intervertebral discs, paraspinal muscles, facet joints, and epidural fat, through both biomechanical and systemic biological pathways. We specifically highlight key mechanisms such as oxidative stress, adipokine signalling, and neuroinflammation that may accelerate spinal degeneration and promote chronic pain. In doing so, we aim to bridge gaps between anatomical, biochemical, and clinical perspectives. Additionally, we assess current clinical evidence on weight loss as a potential strategy for alleviating LBP symptoms. By consolidating diverse lines of evidence, this review provides a clearer framework for understanding obesity-related spinal pathology and outlines priorities for future research and targeted interventions.

1. Introduction

Obesity and low back pain (LBP) are among the most prevalent global health issues, posing substantial socioeconomic challenges and significantly impacting quality of life [1,2,3]. While traditionally considered separate conditions, growing evidence suggests that obesity and LBP are closely interconnected, creating a vicious cycle of chronic pain, reduced mobility, and further weight gain (Figure 1) [4].

Obesity, recognized as a chronic and systemic disorder, contributes to the progression of intervertebral disc (IVD) degeneration (IDD) and LBP [4,5,6]. Research indicates that individuals with obesity have a 1.4 to 1.7 times higher risk of developing chronic LBP [7,8]. Obesity contributes to LBP through both mechanical stress on the spine and biochemical effects, including systemic inflammation and adipokine-induced extracellular matrix (ECM) degradation by disc cells [4]. Additionally, LBP often leads to reduced physical activity, negatively affecting mental well-being, dietary habits, and social interactions, further perpetuating obesity and musculoskeletal decline.

This review aims to elucidate the mechanisms underlying the interplay between obesity and LBP by synthesizing anatomical, biochemical, and biomechanical evidence. Additionally, we highlight gaps in current knowledge and discuss potential strategies to disrupt the vicious obesity and LBP cycle.

2. Obesity

According to the World Health Organization (WHO), obesity is defined as a chronic and complex disorder characterized by excessive fat accumulation with multisystemic involvement. Recent estimates indicate that approximately 2.5 billion adults are overweight, with nearly 900 million living with obesity [9]. Although fat accumulation is often the result of an imbalance between calorie intake and energy expenditure, obesity is a multifactorial disease caused by a combination of genetic, environmental, and psychosocial factors [10].

Being overweight or obese is associated with substantial health risks. In 2019, it was estimated that a higher-than-optimal body mass index (BMI), typically above 25 kg/m², contributed to approximately 5 million deaths from noncommunicable diseases worldwide [11]. Obesity significantly increases the risk of developing a range of serious conditions, including type 2 diabetes, hypertension, chronic kidney disease, liver cirrhosis, cancer, chronic respiratory disorders, and retinopathy, posing a major socioeconomic burden on healthcare systems [12]. In fact, the global medical costs associated with obesity accounted for up to 2.5% of the global Gross Domestic Product in 2020, a figure projected to reach as high as 3% over the next decade [13]. It is important to note that although BMI is commonly used as a proxy for obesity, it fails to differentiate between fat and lean mass, or account for fat distribution, key factors that more accurately predict obesity-related health risks [14,15]. Obesity is not simply excess fat, but a complex pathological state marked by dysfunctional adipose tissue and systemic metabolic disruption. Nonetheless, this distinction is often overlooked in the literature due to practical limitations in clinical and epidemiological assessments. In order to comprehend obesity beyond BMI, it is essential to examine the underlying biological mechanisms that drive its pathophysiology.

The pathophysiology of obesity and associated comorbidities is complex and involves several genetic, epigenetic, environmental, hormonal, and immune mechanisms. Although rare forms of genetic obesity can be attributed to specific mutations [16], most cases are prompted by excessive food intake and unhealthy diet coupled with a sedentary lifestyle, ultimately leading to a caloric energy surplus and fat accumulation [17]. That said, new emerging evidence suggests that exposure to microplastics and their associated chemical burden may also contribute to obesity by inducing alterations in endocrine function and disrupting metabolic processes [18,19,20]. Increased and dysfunctional white adipose tissue deposits are metabolically active and secrete a wide array of adipokines and pro-inflammatory cytokines, which disrupt nutrient metabolism, alter hormone release (e.g., glucagon-like peptide [GLP]-1, oxyntomodulin, peptide tyrosine-tyrosine, cholecystokinin [CCK], etc.), and modulate food consumption behaviours, eventually establishing a chronic, systemic, low-grade inflammatory state [17]. In addition, disruptions in hormone regulation, including thyroid-stimulating hormone (TSH) and cortisol, may predispose individuals to conditions such as hypothyroidism, Cushing’s syndrome, and polycystic ovary syndrome [21]. Nonetheless, systemic inflammation also leads to accelerated atherosclerosis and resulting macro- and microangiopathy, which may result in increased risks of ischemic heart disease, stroke, peripheral artery disease, etc. [17]. In short, obesity is a complex, multifactorial disorder that affects nearly all organs and physiological systems, significantly reducing both life expectancy and quality of life.

3. Low Back Pain

LBP is the most prevalent musculoskeletal condition worldwide, impacting nearly 570 million people and representing the leading cause of disability across all age groups [2]. Notably, symptoms can begin as early as childhood, with cases reported in children as young as 10 years old [22,23], and seemingly is on the rise in this young cohort [24]. LBP affects all populations, but certain risk factors are associated with a higher incidence and severity. These include age, genetic predisposition, obesity, smoking, and a sedentary lifestyle [25,26]. Among workers, LBP is a leading cause of absenteeism and reduced productivity, imposing a significant economic burden on healthcare systems worldwide [2,27].

LBP can arise from various sources, including muscular strain, ligament injuries, facet joint degeneration, and IDD [28,29]. IDD is particularly common and often necessitates medical intervention or, in severe cases, surgical intervention. The IVDs, located between the vertebrae, are essential for spinal mobility, flexibility, and load distribution. Each IVD consists of a collagen-fibre-rich annulus fibrosus (AF) that surrounds the gel-like nucleus pulposus (NP) at its centre. These two tissues are separated from the vertebral bodies via interposition of two cartilaginous layers, namely the cartilaginous endplates (CEPs), which are essential for IVD integrity and IVD nourishment. Over time, age-related factors, mechanical stress, and metabolic changes can compromise IVD integrity, leading to IDD [28,30]. This process is characterized by a loss of NP hydration, reduced proteoglycan and collagen content, and the formation of fissures within the AF. IDD impairs the shock absorption and force distribution capacities of the IVD, stressing NP and AF cells. This promotes IVD cells to release a plethora of enzymes, such as matrix metalloproteinases (MMPs), that facilitate ECM breakdown, leading to acceleration of disc dehydration, disc height loss, and mechanical instability [31]. Additionally, structural degeneration of the AF diminishes its ability to contain the swelling of the NP, potentially resulting in disc bulging, AF rupture, or disc herniation [30,32]. Furthermore, pro-inflammatory cytokines (e.g., interleukin [IL]-1β, tumour necrosis factor [TNF]-α) released by disc cells may exacerbate this cycle, by causing increased catabolic enzyme activity, oxidative stress, and cellular apoptosis [28,33,34,35]. These cytokines may also sensitize nerve endings [36,37,38] and promote the influx of immunogenic cells into the otherwise largely immune-compromised IVD [39,40,41], further contributing to LBP.

The treatment for LBP, especially discogenic LBP related to IDD, generally encompasses conservative intervention, and for most cases the condition will only present temporarily [42]. Here, conservative management typically includes physical therapy, pharmacological interventions (e.g., nonsteroidal anti-inflammatory drugs [NSAIDs], corticosteroids, etc.), and lifestyle modifications [43]. For patients with persistent pain who do not respond to conservative measures, surgical interventions, such as discectomy or spinal fusion, may be considered [44]. However, these surgical procedures often fail to restore full disc function and may lead to long-term complications, including reduced range of motion (ROM) and adjacent segment degeneration [45]. Moreover, long-term pain and disability benefits remain disputed [46,47]. While current therapies aim to relieve symptoms and stabilize the spine, they do not reverse or repair the degenerative changes within the disc [48]. This lack of restoration has driven interest in regenerative medicine as a promising approach to treat IDD and LBP [49]. Regenerative strategies, including cell-based therapies [50,51,52], biomaterial scaffolds [53,54,55], and extracellular vesicle injections [56,57,58] are designed to regenerate the IVD tissue, restore disc hydration, and bring back its mechanical function, thereby potentially delaying, halting, or even reversing IDD. However, these strategies remain in their initial stages of clinical development and encounter substantial translational hurdles [59,60,61,62].

4. Spinal Changes Related to Obesity

Epidemiological studies have consistently shown a strong correlation between elevated BMI and the prevalence of LBP (Figure 2). Sheng et al. found higher LBP and IDD risk in overweight and obese individuals, but no significant link with spondylosis or cervical disorders [63]. Additional factors, such as waist circumference, body fat percentage, and fat-free mass (i.e., all non-fat components of the body), were causally linked to increased risks of IDD and sciatica. Adjusting for BMI, whole-body fat-free mass maintained a significant association with the risk of IDD [64].

A systematic review of twin studies by Dario et al. [65] examined the relationship between obesity, LBP, and lumbar IDD, highlighting that while obesity correlates with these conditions, genetic and early environmental factors also play a significant role. Similarly, a prospective study by Segar et al. [66] assessed the relationship between BMI and spinal pathologies, including IDD, disc herniation, and spinal stenosis. Their findings showed BMI modestly predicted IDD but was more strongly linked to disc herniation and spinal stenosis, especially in the upper lumbar spine. Obesity-related LBP involves mechanical stress, systemic inflammation, and metabolic disturbances, contributing to degeneration of the IVD, facet joints, paraspinal muscles (PSMs), and epidural fat, which are further discussed below (

Table 1. Overview of obesity-related changes associated with IDD and LBP.

Tissue	Structural Changes	Functional Changes	Ref
NP	Loss of proteoglycans Decreased water content AGE accumulation Fibrotic changes	Reduced ability to resist compression Loss of mechanical shock absorption Loss in spinal height and stability	[33,67,68,69]
AF	Disruption of lamellar structure AGE accumulation Fibrotic changes Microtears	Decreased tensile strength and increased stiffness Loss of structural integrity and containment of NP	[70,71]
CEP	Thinning and calcification Impaired permeability Microfractures	Reduced nutrient and waste exchange Loss of NP environment containment Development of focal defects	[64,72,73,74,75,76,77,78,79]
Facet joints	Osteoarthritic changes Joint effusion	Reduced spinal stability Compression of neighbouring tissues	[80,81,82]
PSMs	Increased fatty infiltration Reduced muscle fibre size Muscle atrophy	Reduced spinal stability Decreased endurance and strength	[83,84,85]
Epidural fat	Excessive fat accumulation Compression of adjacent nervous structures	Increased risk of spinal stenosis and cauda equina syndrome Compression-related pain	[86,87,88,89,90]

Abbreviations: AF (annulus fibrosus); AGE (advanced glycation end-product); CEP (cartilaginous endplate); NP (nucleus pulposus); PSM (paraspinal muscle).

).

4.1. Intervertebral Disc

Within the IVD, the NP and AF are particularly vulnerable to the metabolic stress associated with obesity. Obesity triggers chronic low-grade inflammation marked by elevated pro-inflammatory cytokines, which promote ECM degradation through increased matrix-degrading enzymes and cellular stress, while apoptosis and senescence reduce ECM-producing cells [33]. Here, the primary endocrine and paracrine mediators of this obesity-induced metabolic dysfunction are likely adipokines [91], whose role is described in detail below.

The connection between obesity and IDD has been well documented in preclinical animal models. Experimental mouse models subjected to high-fat diets (HFD), which result in elevated systemic lipid levels, exhibit altered IVD metabolism characterized by increased apoptosis and ECM degradation [67,68,92]. Similar degenerative changes are observed in other cartilage tissues, such as knee joints [67]. These ECM changes are accompanied by a loss of disc height, reduced hydration, and a significant increase in inflammatory factors such as TNF-α, Monocyte Chemoattractant Protein (MCP)-1, vascular endothelial growth factor (VEGF), and IL-1β [67,68]. Since obesity is often accompanied by diabetes, it is noteworthy that hyperglycemia can directly impair IVD integrity in murine models. While hyperglycemia can increase the glycosaminoglycan and collagen content of the disc, it also promotes the accumulation of advanced glycation end-products (AGEs), leading to disorganized AF lamellae and reduced mechanical strength and elasticity [70]. In a mouse model, excessive dietary AGE intake resulted in increased collagen cross-linking and AF damage, ultimately leading to higher IVD compressive stiffness, torque range, and failure torque, particularly in female animals [71]. Additionally, glucose may dose-dependently upregulate a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4 and -5 through activation of the CREB-binding protein (CBP)-PPARγ coactivator 1α (PGC1α)-Runx2 complex, further contributing to IVD ECM breakdown [69].

Like the NP and AF, the CEP is also vulnerable to obesity-induced mechanical, metabolic, and inflammatory stressors, which heighten the risk of microfractures and structural damage. Additionally, elevated lipid levels and associated atherosclerosis in endplate vasculature are exhibited [4,93], while metabolic and inflammatory changes promote CEP thinning and calcification [72,73], thereby reducing CEP permeability and hindering essential nutrient and waste transport required for IVD homeostasis [94]. Specifically, Apolipoprotein E (ApoE), a crucial lipid metabolism regulator, has been shown to worsen CEP degeneration when deficient, largely via adipokine-mediated signalling pathways [95]. Elevated adipokine levels, such as leptin and resistin, accelerate CEP thinning and calcification while promoting chondrocyte and osteocyte senescence and apoptosis [74]. However, the clinical relevance of these findings remains uncertain. While some studies suggest that high BMI predisposes individuals to CEP defects, others have reported conflicting evidence [64,75,76]. Retrospective studies have found a higher prevalence of CEP alterations, including Schmorl’s nodes and Modic changes, in both obese children [77] and adults [78,79]. Collectively, these findings indicate that obesity-induced metabolic and inflammatory stressors compromise all IVD components (including the NP, AF, and CEP), consequently impacting homeostasis of other disc tissues, and thereby driving a multifaceted degenerative cascade (Figure 2). Critically, however, further clinical studies are needed to better clarify these associations in the human spinal tissues.

4.2. Facet Joints

Obesity exacerbates facet joint osteoarthritis primarily through mechanical overload and systemic inflammation, accelerating cartilage degradation, subchondral bone remodelling, and osteophyte formation, which collectively may contribute to pain and restricted mobility [80]. Inflammatory pathways also play a critical role, as elevated cytokine levels in obesity amplify catabolic activity within joint tissues, promoting ECM degradation and impairing cartilage repair. This imbalance weakens the subchondral bone supporting the facet joints, making it more prone to degeneration and microfractures (Figure 2). Additionally, lipid abnormalities further contribute by enhancing osteoclast activity and inhibiting osteoblast differentiation, resulting in a compromised bone microenvironment [96]. Interestingly, despite similar prevalence rates of facet joint-related LBP in obese and non-obese individuals based on BMI [81], obese patients have been reported to experience less pain relief following radiofrequency ablation treatments [82]. Moreover, another study found an association between increased outer abdominal fat thickness and higher rates of facet joint osteoarthritis, suggesting that fat distribution, rather than BMI alone, may influence facet joint degeneration [80].

4.3. Paraspinal Muscles

Excessive body weight significantly impacts PSMs, leading to fatigue, reduced strength, and an increased risk of strain injuries. Obesity is strongly associated with greater fatty infiltration in these muscles, particularly in women, compromising muscle quality and spinal stability [83]. As muscle fibres are replaced by adipose tissue, functional muscle mass and strength decline, resulting in a condition known as sarcopenic obesity [97]. Fatty degeneration of the PSMs is often classified using Kalichman’s scoring system (in short defined as the following: grade 1, indicating normal muscle with fatty infiltration up to 10% of the muscle’s cross-sectional area; grade 2, moderate degeneration with 10–50% fatty infiltration; and grade 3, severe degeneration with over 50% fatty infiltration) [98]. These changes reduce the functional capacity of PSMs, increase mechanical stress on the spine, and accelerate spinal degeneration, contributing to the chronicity of LBP in individuals with obesity [85]. Fat infiltration increases with both BMI and age, as demonstrated by Peng et al. [99], who reported that the combined fat infiltration ratio of the multifidus and erector spinae muscles rises from 9.7% ± 5.0% in individuals aged 40–49 years to 25.8% ± 7.6% in those aged 70–79 years. Concurrently, multifidus and external oblique muscle thickness decreases with increasing BMI, particularly in LBP patients [84]. Notably, reduced muscle quality at the upper lumbar levels increases mechanical stress on the lower lumbar segments, accelerating spinal degeneration and exacerbating chronic pain [85]. This redistribution of load and reduced stability further perpetuate the cycle of obesity, inactivity, and spinal dysfunction, emphasizing the critical role of maintaining muscle integrity to mitigate LBP in obese individuals (Figure 2). Here, strengthening the PSM through targeted exercise may enhance spinal stability, reduce mechanical strain, and serve as a protective factor against the development and progression of LBP [100].

4.4. Epidural Fat

Epidural fat is adipose tissue within the spinal canal that surrounds the dura mater, cushioning the spinal cord and nerve roots. In certain cases, excessive epidural fat accumulation (particularly in obesity) can lead to spinal stenosis by compressing neural structures, resulting in pain, numbness, and weakness in the lower extremities, a condition known as epidural lipomatosis [86]. A recent longitudinal study demonstrated a linear relationship between BMI and epidural fat volume, with each 1 kg/m² increase in BMI corresponding to an additional 45 mm³ of epidural fat [87]. Similarly, Cushnie et al. reported greater epidural fat volume in obese patients undergoing urgent decompression for cauda equina syndrome, suggesting that epidural lipomatosis may increase the risk of this condition in obese individuals [88]. This association was further supported by a recent meta-analysis, which identified increased BMI as the primary risk factor for epidural lipomatosis and suggested that weight loss could mitigate symptom severity and surgical complications [89]. Beyond its mechanical effects, epidural fat accumulation has been recognized as a marker of metabolic syndrome (Figure 2). Studies have shown that its volume correlates not only with BMI but also with abdominal circumference, visceral fat area, and hypertension. From this perspective, epidural lipomatosis may represent a form of ectopic fat deposition, similar to that seen in the pancreas, heart, and liver in patients with metabolic syndrome [90]. Adipocytes from overweight patients undergoing decompression surgery for epidural lipomatosis were found to be hypertrophic and exhibited increased expression of pro-inflammatory cytokines such as TNF-α and IL-1β [101]. However, further mechanistic studies are needed to validate these findings.

4.5. Nervous System

Interestingly, the promotion of degenerative and catabolic changes consequential to obesity not only changes the ECM and biochemistry of the affected tissues but also seems able to directly impact pain and behavioural changes. For example, in the work of Kerr et al. [67], the authors highlighted that both their HFD and “western diet” fed mice showed significant enhancements in the mechanical sensitivity and lower rates of mobility that preceded structural joint deterioration. More directly, HFDs have been shown to alter nerve and brain activity in rats by inducing neuroinflammation and disrupting metabolic signalling, which may sensitize pain pathways and exacerbate nociceptive responses [102]. This could partially explain the heightened perception of pain and increased susceptibility to IDD and LBP observed in obese patients, however this direct link requires more extensive investigation, especially in humans (Figure 2).

In a similar vein, the enhanced circulation of adipokines such as leptin and lipocalin-2 (LCN2) may further modulate neuroinflammatory processes involved in pain and mood regulation [103,104]. They are able to amplify the neuroinflammatory triad and contribute to central sensitization, a key feature of chronic pain states. Leptin, in particular, has been shown to enhance nociceptive signalling within the spinal cord and brain, while also influencing mood-related circuits [105,106]. These observations suggest that obesity-associated alterations in adipokine profiles not only drive inflammation and degeneration but also play a direct role in amplifying pain perception and emotional dysregulation stemming from both metabolic disorders and spinal degenerative changes.

5. The Biomechanical Impact of Obesity on the Spine

Overweight and obesity have long been recognized as major contributors to IDD and discogenic LBP, primarily due to the biomechanical overloading they place on the IVDs and spinal structures, particularly in the lumbar spine [3,6]. Studies indicate that individuals with excess weight have a significantly higher risk of developing chronic LBP, surpassing the influence of age and sex [107]. Furthermore, obesity increases the likelihood of developing IDD by up to 1.8 times [108], and raises the risk of lumbar disc herniations that may require surgical intervention [30]. Notably, weight loss after bariatric surgery has been suggested to improve LBP intensity and related disability [109], as well as L4-L5 disc height [110].

The biomechanical factors associated with increased IDD in overweight and obese individuals are related to a combination of the following factors: (1) overloading that exceeds the strength threshold of IVD tissues, (2) spinal joint instability caused by hypermobility under increased loads, and (3) cyclic loading under repetitive conditions exceeding the inherent tissue healing capacity [111]. Importantly, not only BMI, but also body shape and fat distribution may differentially affect spinal loading. Central obesity, characterized by accumulation of abdominal fat and a higher waist-to-hip ratio, is particularly associated with greater spinal forces, possibly causing damage to the IVDs and vertebrae [111]. These observations were confirmed by a recent meta-analysis, which showed that waist circumference and waist-to-hip ratio were associated with an increased risk of chronic LBP [112].

Obesity-related postural changes also affect spinal biomechanics. A recent study by Bayartai et al. [113] demonstrated that adults with obesity are characterized by increased thoracic kyphosis and decreased thoracic and lumbar flexion-extension ROM, a pattern previously noted in obese children and adolescents with and without idiopathic scoliosis [114]. On the other hand, reduced spine mobility in obese individuals may be attributed to several factors, including the increased soft tissue mass and more severe osteoarthritic changes. In a cadaveric study, Rodriguez-Martinez and coauthors [115] found that L4-L5 specimens from obese subjects exhibited greater facet joint degeneration and a higher prevalence of disc herniations. Additionally, a negative correlation between BMI and both flexion–extension ROM and axial compressive stiffness was noted, although significant only in female specimens [115]. Apart from postural features, overweight status has been shown to also impact dynamic activities. A finite-element study demonstrated that obese individuals experience around 40% higher compression and shear stress at the L5-S1 level during lifting activities, independent of hand position [116]. This finding implies that even postural adjustments (e.g., use of braces) may not effectively counterbalance the increased spinal loads in obese individuals [116]. Increased segmental overloading in distal lumbar segments has also been confirmed in vivo. In a recent study, Coppock et al. [117] compared lumbar IVD deformation before and after treadmill walking. Intriguingly, the authors demonstrated that post-exercise magnetic resonance imaging (MRI) showed that increasing BMI was associated with significantly higher strain in the L5-S1 disc.

Increased IDD in overweight and obese individuals may also be partly attributed to poor PSM quality due to fatty infiltration, as mentioned above. In physiological conditions, PSMs are essential for a balanced load distribution across the spine and proper postural control. Therefore, muscle imbalances and/or a reduction in functional muscle mass (e.g., loss of fibres due to atrophy or fatty substitution) diminish the net capacity of the muscle tissues to stabilize the spine and resist displacement forces [118]. It has been previously shown that patients with LBP have thinner core muscles and fewer type 1 fibres in the multifidus muscles, which are crucial for maintaining muscle tone and endurance [119]. In line with these findings, Ozcan-Eksi and colleagues [85] recently found that obese patients exhibit more severe IDD, a higher prevalence of Modic changes at lower lumbar levels, and increased fatty infiltration in the upper lumbar spine. Similarly, Ucar et al. [84] demonstrated that individuals with nonspecific LBP and high BMI had reduced thickness and increased fatty infiltration of abdominal and PSMs, which were linked to higher disability scores according to the Oswestry Disability Index (ODI). Collectively, these findings highlight how excess body weight compromises spinal biomechanics, amplifies mechanical stress, alters muscle adaptability, and ultimately accelerates degenerative changes across all spinal tissues (Figure 2).

6. The Biochemical Impact of Obesity on the Spine

Obesity-related biochemical disruptions—including systemic inflammation, lipid dysregulation, and metabolic imbalances—create a catabolic, pro-inflammatory microenvironment enriched with cytokines such as TNF-α and IL-6 [120,121]. Oxidative stress further aggravates this state by inducing apoptosis, senescence, and mitochondrial dysfunction, further weakening disc biology [122]. Impaired nutrient diffusion to the avascular IVD compounds these effects, accelerating degeneration and linking obesity to IDD and LBP [74,123]. The following sections examine key biochemical drivers of obesity-related IDD and their roles in spinal degeneration.

6.1. Lipid Dysregulation

Lipid dysregulation refers to imbalances in lipid metabolism and transport, often marked by elevated levels of circulating fatty acids that disrupt cellular homeostasis and promote inflammation [124]. Obesity is associated with profound alterations in lipid metabolism [92], including dysregulated lipid profiles, characterized by elevated free fatty acids, triglycerides, and cholesterol, thus contributing to both systemic and local inflammation [125]. For the spine, excessive lipid deposition in vertebral marrow adipose tissue (MAT) correlates with impaired disc hydration, reduced cell viability, and increased production of MMP and ADAMTS enzymes [83]. Lipotoxicity from excess saturated fatty acids, such as palmitic acid, impairs mitochondrial function, triggering lipid accumulation, oxidative and endoplasmic reticulum (ER) stress, and intrinsic apoptosis [126]. This promotes a senescent phenotype in disc cells, worsening spinal degeneration and underscoring the importance of lipid regulation in obesity-related IDD [127]. Oxidized low-density lipoprotein (LDL) increases mitochondrial reactive oxygen species (ROS) and triggers apoptosis [128], while oxidative stress-induced ferroptosis in AF and NP cells further aggravates degeneration [129]. Inflammatory and metabolic disturbances also induce ER stress, which disrupts ECM protein regulation and lipid metabolism, impacting adipocyte differentiation, which consequentially alters fatty acid synthesis and triglyceride secretion [130]. These changes collectively accelerate ECM degradation, thereby driving IDD progression [131]. Altogether, these lipid-driven disturbances in obesity contribute significantly to spinal tissue degeneration, emphasizing the need to further elucidate the underlying mechanisms of lipid homeostasis in IVD health.

6.2. Metabolic Alterations

A range of metabolic disturbances are commonly observed in obesity, including insulin resistance, hyperglycemia, and impaired cellular energy regulation [68]. Due to the avascular nature of the IVD [72], disc cells reside in a hypoxic, low-glucose environment and have adapted to survive under limited nutrient conditions [94,95,132,133]. However, systemic metabolic dysfunctions can overwhelm these adaptations and adversely affect disc cell viability and function. For instance, hyperglycemia has been shown to promote the accumulation of AGEs, which stiffen ECM components, within the IVD [134]. AGEs also activate the receptor for AGEs (RAGE), triggering inflammatory pathways that upregulate matrix-degrading enzymes such as MMPs and ADAMTS, while also inducing apoptosis [135]. This cascade reduces proteoglycan content and undermines ECM integrity, contributing to IDD, pain, and dysfunction. Additionally, insulin resistance and mitochondrial impairments in obesity disrupt disc cell energy homeostasis, leading to reduced adenosine triphosphate (ATP) production and increased apoptosis [136]. Together, these metabolic alterations impair disc homeostasis, accelerating IDD and reinforcing the link between obesity and LBP.

6.3. The Adipokine Cascade

Adipokines are bioactive signalling molecules secreted by adipose tissue that regulate immune responses, inflammation, and tissue remodelling. In obesity, adipose tissue enters a chronic low-grade inflammatory state, characterized by elevated levels of pro-inflammatory adipokines, such as leptin, resistin, and LCN2, and decreased levels of anti-inflammatory molecules like adiponectin [137] (

Table 2. Overview of obesity-related dysregulated adipokines and their association with IDD.

Adipokine	Type	Function	Effect on IDD	Refs.
CCL2	Chemokine	Regulates immune cell migration. Involved in neuroinflammation.	Increases macrophage infiltration, enhances NF-κB activation, and contributes to IDD.	[145,146,147,148,149]
CXCL5	Chemokine	Pro-inflammatory mediator and attractant for granulocytes.	Elevated in LBP and IDD models and Modic-change patients.	[150,151,152]
Progranulin	Cytokine	Autocrine growth factor promoting chondrocyte differentiation and proliferation. Implicated in inflammation, host defence, wound healing, and rheumatic diseases.	Increases MMP-13, ADAMTS-5, and iNOS in AF and CEP cells. Activates NF-κB, Wnt–β-catenin signalling. It is increased in IDD and positively related to its clinical symptoms, playing a protecting role by inducing IL-10, reducing IL-17.	[153,154,155,156]
Lipocalin-2	Cytokine	Pro-inflammatory adipokine regulating hematopoietic apoptosis, immune responses, and metabolic homeostasis. Acts as a sensor of mechanical load and inflammation.	Increases MMP9 activity via nerve growth factor. Promotes IDD through LCN2/NF-κB axis.	[138,143]
Chemerin	Cytokine	Links innate and adaptive immunity. Interacts with CMKLR1 to regulate inflammation.	Activates NF-κB via CMKLR1 and TLR4. Increases inflammatory mediators leading to ECM degradation. Chemerin and CMKLR1 increase with IDD, especially in obese individuals.	[157]
ANGPTL2	Cytokine	Signalling pathway mediator in chronic low-grade inflammatory diseases, including obesity, diabetes mellitus, and cardiovascular diseases. Potential target of TGF-β, contributing to capillary formation.	Its upregulation aggravates inflammation and fibrosis in NP cells. Induced by TGF-β1 overexpression triggered by IL-1β. Promotes IDD by increasing IL-6, TNF-α, collagen I, and collagen III expression.	[158,159]
TNF-α	Cytokine	Multifunctional cytokine involved in autoimmune diseases and inflammatory responses. Strongly promotes interleukins and MMP production.	Promotes inflammation, induces IL-1, IL-17. Increases ECM degrading metalloproteinases leading to IDD.	[160]
Interleukins	Cytokine	Interleukins are a diverse family of cytokines regulating immune responses. IL-1 and IL-6 drive inflammation and share functional overlap with TLR signalling. IL-17 and IL-18 amplify autoimmune and inflammatory pathways, while IL-10 acts as a key anti-inflammatory mediator, limiting immune cell activation.	IL-1 triggers inflammatory cascades that drive IDD progression. IL-6 promotes IDD through ERK/JNK/p38 signalling and is elevated in IDD patients. IL-18 accelerates ECM degradation by upregulating MMP13 and downregulating type II collagen and SOX6 but may also exert protective effects by inhibiting caspase-3/9-dependent apoptosis. IL-17 is increased in lumbar disc herniation, enhancing inflammation and immune activation. IL-10, found at higher levels in IDD patients, regulates immune responses with potential anti-inflammatory effects.	[144,152,154,161,162,163,164,165,166,167]
SFRP5	Cytokine	Anti-inflammatory adipokine. Blocks WNT5A signalling, regulating inflammation, proliferation, and differentiation.	Upregulated in NP growth. Plays a role in laminin and BMP receptor binding pathways.	[168,169]
Leptin	Hormone	Regulates appetite and energy balance via LepR and modulates innate immunity. Stimulates pro-inflammatory cytokine release and influences insulin secretion, lipid metabolism, thermogenesis, angiogenesis, and bone/cartilage homeostasis.	Expression in NP and AF cells. Increases cell proliferation, proteolytic enzyme synthesis, NO production. Reduces aggrecan levels, induces differentiation, regulates CEP degeneration, and inhibits apoptosis of NP cells.	[74,125,139,141,170,171,172,173]
Adiponectin	Hormone	Anti-inflammatory properties, promoting fatty acid oxidation and glucose uptake. Implicated in metabolic syndrome, cardiovascular diseases, osteoarthritis, and rheumatoid arthritis.	Increases TNF secretion in AF cells, reduces TNF in NP cells, expression reduced in degenerated NP cells. Exert anti-inflammatory effects in diseased disc tissues. Conflicting evidence regarding AdipoR1, AdipoR2 expression in NP cells.	[138,174,175,176]
Visfatin	Hormone	Expressed in visceral fat and involved in energy metabolism and inflammation. It promotes inflammatory cytokine production and modulates MAPK and NF-κB signalling pathways. Its expression is upregulated under hypoxic conditions, linking it to metabolic stress and inflammatory responses.	Highly concentrated in NP cells with severe IDD. Expression increased by IL-1β. Regulates autophagy. Promotes IL-6 production, mediates IL-1β-induced NP cell degeneration and apoptosis.	[127,144,177,178]
Resistin	Hormone	Links obesity and diabetes by promoting insulin resistance. Modulates angiogenesis and inflammatory environments in joints.	Highly expressed in degenerative disc cells. Increases ADAMTS-5 and CCL4 in NP cells. Promotes IDD via p38 MAPK. Enhances inflammatory responses and MMP expression.	[136,179,180]
Ghrelin	Hormone	Involved in growth hormone secretion, appetite regulation, glucose metabolism, bone/cartilage metabolism.	Counteracts IL-1-induced catabolic effects. Reduces IL-1β-induced ADAMTS-5, MMP-13, TNF-α. Induces ECM production via GHSR activation.	[181]
Omentin-1	Hormone	Anti-inflammatory adipokine involved in immunity and metabolic processes. Its expression level is inversely correlated with the progression of various diseases, including diabetes, obesity, and osteoarthritis.	Activates PI3K/Akt and SIRT1 pathways. Protects NP cells from inflammation and apoptosis induced by IL-1β.	[169,182]

Abbreviations: LepR (leptin receptor); NP (nucleus pulposus); AF (annulus fibrosus); NO (nitric oxide); CEP (cartilaginous endplate); MMP (matrix metalloproteinase); ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs); iNOS (inducible nitric oxide synthase); NF-κB (nuclear factor kappa B); Wnt (wingless/integrated signalling pathway); MAPK (mitogen-activated protein kinase); IDD (intervertebral disc degeneration); IL (interleukin); CCL2 (C-C motif chemokine ligand 2); CMKLR1 (chemokine-like receptor 1); ECM (extracellular matrix); GHSR (growth hormone secretagogue receptor); PI3K (phosphoinositide 3-kinase); Akt (protein kinase B); SIRT1 (sirtuin 1); ANGPTL2 (angiopoietin-like protein 2); TGF-β (transforming growth factor β); TLR (toll-like receptor); ERK (extracellular signal-regulated kinase); JNK (c-Jun N-terminal kinase); p38 (p38 mitogen-activated protein kinase); SOX6 (SRY-box transcription factor 6).

). This imbalance perpetuates systemic inflammation and metabolic dysfunction, contributing to the pathogenesis of IDD. Dysregulated adipokine signalling promotes ECM degradation, oxidative stress, and apoptosis in IVD cells, primarily via Toll-like receptor (TLR)-mediated pathways [138,139]. In particular, pro-inflammatory adipokines like leptin as well as immune mediators secreted by vertebral MAT have been shown to exacerbate IDD [140]. Leptin and resistin, both elevated in obesity, enhance ECM breakdown, upregulate inflammatory cytokines, and induce IVD cell apoptosis [136,141]. Conversely, adiponectin, typically anti-inflammatory, is reduced in obesity. However, its role in IDD appears to be context-dependent, with evidence suggesting it may still activate inflammatory signalling under certain conditions [142]. Additional adipokines, such as LCN2 and visfatin, further drive degeneration, i.e., LCN2 activates NF-κB and increases MMP9 activity, while visfatin promotes IL-6 production and mediates IL-1β-induced apoptosis in NP cells [138,143,144]. Together, these alterations in adipokine secretion (Table 2) foster a pro-inflammatory, catabolic microenvironment within the disc (as well as other spinal tissues), accelerating degeneration and reinforcing the mechanistic link between obesity and IDD.

Adipokines also influence pain pathways, potentially amplifying pain perception in obesity-related LBP. Leptin and resistin, for instance, can promote IL-1 synthesis, sensitizing nociceptors and enhancing central pain processing [183,184]. Leptin, along with its receptor (LepR), is expressed in dorsal root ganglion neurons and contributes to neuropathic pain by upregulating N-methyl-D-aspartate receptor (NMDAR) subunits, increasing neuronal nitric oxide synthase, and intensifying pain signalling. These effects link systemic inflammation to heightened pain severity [185]. Neuromodulation therapies, such as spinal cord stimulation, have demonstrated the potential to modulate adipokine levels, suggesting a link between metabolic regulation and pain management [111]. Similarly, LCN2 exacerbates neuroinflammation by promoting microglial activation [186], increasing pro-inflammatory cytokine release, and enhancing neuronal sensitivity, all of which contribute to pain hypersensitivity in obesity-related LBP [186,187]. Despite growing insights into the biochemical interplay between obesity, IDD, and pain, key knowledge gaps remain. Future studies should investigate how adipokines interact, their regulatory networks in disc cells, and their roles in IDD progression and pain severity. Longitudinal and mechanistic research could support the development of adipokine-targeting therapies to modulate inflammation, disc metabolism, and nociception. Additionally, stratifying patients by adipokine profiles may help enable personalized treatment approaches [188,189].

6.4. Gut Microbiome and Metabolic Inflammation

The gut microbiome, a complex community of microorganisms residing in the gastrointestinal tract, plays a crucial role in maintaining metabolic homeostasis, immune regulation, and inflammation control. Dysbiosis [190], an imbalance in microbial composition, can disrupt these processes, leading to increased intestinal permeability, systemic inflammation, and metabolic dysfunction. Emerging evidence suggests that obesity is associated with gut microbiome alterations, characterized by reduced microbial diversity, an increased Firmicutes-to-Bacteroidetes ratio, and an enrichment of pro-inflammatory species [191,192,193]. This dysbiotic state contributes to systemic inflammation and metabolic dysfunction, ultimately promoting IDD [194]. Specifically, the altered gut microbiota composition promotes intestinal permeability, facilitating endotoxin (lipopolysaccharide; LPS) translocation into circulation, which generally triggers chronic low-grade inflammation via TLR-4 signalling, systematically affecting local tissues [195]. Furthermore, the microbiome-driven inflammation exacerbates insulin resistance, oxidative stress, and cytokine production, all of which have shown to be linked to ECM degradation and cell apoptosis within the disc [196]. Although the gut–spine axis offers a promising target for therapeutic intervention in obesity-related IDD, inconsistencies across studies currently limit its clinical application [191,197]. Methodological consistency and continued research are crucial to clarify the underlying mechanisms and confirm the therapeutic potential of the gut–spine axis.

6.5. Hypoxia and Angiogenesis

Due to its avascularity, the IVD relies on CEP-mediated diffusion for oxygen and nutrients. In obesity, metabolic stress and inflammation raise oxygen demand while hindering diffusion, causing systemic and local hypoxia [198]. Adipose tissue hypoxia, driven by obesity-related adenine nucleotide translocase 2 (ANT2)-mediated mitochondrial uncoupling, increases oxygen use, activates hypoxia-inducible factor (HIF)-1α, and promotes chronic inflammation [199]. These pathophysiological changes parallel those in the IVD, where obesity-induced CEP sclerosis restricts oxygen diffusion, and adipokine-mediated endothelial dysfunction impairs vascular homeostasis [200]. In response to hypoxia, HIF signalling is activated to promote cellular adaptation; however, prolonged HIF-1α activation also upregulates VEGF, contributing to pathological angiogenesis [201,202]. This hypoxia-driven neovascularization is a recognized feature of IDD and may reflect similar mechanisms observed in other degenerative tissues [38,72]. Obesity contributes to IDD and LBP through a dual mechanism: aggravating hypoxia and promoting pathological vascularization. Elevated systemic and local hypoxia intensifies catabolic activity in the NP, accelerating degeneration [203,204,205]. Simultaneously, obesity-driven neovascularization may compromise the IVD’s immune-privileged status [40], facilitating nociceptor sensitization, inflammatory cell infiltration into the IVD, and a spread of systemic obesity-related inflammation into the IVD-environment (Figure 1) [28,36]. This interplay between hypoxia, angiogenesis, and chronic inflammation reinforces a cycle of progressive IDD and pain and warrants more careful study.

In short, obesity profoundly impacts spinal health by inducing systemic and local inflammation, oxidative stress, lipid dysregulation, and metabolic disturbances, all of which accelerate IDD and LBP. Dysregulated adipokines, gut microbiome alterations, and hypoxia-driven angiogenesis create a pro-inflammatory, catabolic microenvironment that disrupts disc homeostasis. Future research should prioritize mechanistic studies and clinical investigations to harness these insights for the development of targeted, personalized interventions of LBP in obese and overweight individuals.

7. Therapeutic Strategies Targeting the Obesity–LBP Connection

7.1. Addressing Obesity as a Pathway to Alleviate LBP

Weight loss, improved dietary habits, and increased physical activity are associated with numerous health benefits [206,207]. Given the established connections between obesity, back pain, and IDD, these interventions hold promise as strategies for prevention and relief. Moreover, for LBP specifically, exercise has been shown to be therapeutic and preventative [208,209,210,211], and direct links have been made with enhanced muscle strength and reduced LBP risk [212]. The high prevalence of physical inactivity among individuals with obesity (often influenced by both physical limitations and motivational challenges) may thus further compound their risk of developing LBP [213,214]. Moreover, although speculative, by reducing mechanical stress on the spine and enhancing spinal stability, weight loss may alleviate pressure and strain on IVDs and vertebral structures [5], while also mitigating systemic and local inflammation—factors implicated in both obesity and IDD [4]. Moreover, the psychological benefits, such as improved mental well-being and self-esteem [215,216], can foster a more active lifestyle conducive to spinal health. Moreover, a poor mental state, such a depression, has been associated with the worsening of pain symptoms [217,218]. Thus, this multifaceted condition underscores a likely beneficial role of lifestyle modifications in managing back pain and promoting spinal health.

Given the established link between high BMI and increased risk of LBP, it seems logical to consider body weight control as a strategy for managing or alleviating LBP. However, despite this connection, research on weight control strategies for LBP relief is limited and often lacks quality. The overall evidence supporting weight loss as a method to alleviate chronic LBP remains inconclusive. For example, the 2023 WHO guideline for non-surgical management of chronic primary LBP [43] does not specifically recommend weight loss as a therapy for LBP and even advises against pharmacological weight management, both due to very low certainty of evidence. This recommendation reflects the very weak evidence base linking weight loss to improved pain or function, despite obesity’s well-established association with LBP severity. Similarly, a recent systematic review by Chen et al. [219] on weight loss programmes and interventions to alleviate LBP was only able to include 11 trials spanning 689 participants. They similarly concluded “there is only very low-quality evidence that some weight loss interventions lead to improvements in LBP and disability” [219]. If we consider the literature, three specific methods to promote weight or fat loss can be distinguished: (1) lifestyle, i.e., changes to calorie and macro-nutrient intake as well as promoting exercise, (2) surgical, e.g., gastric bypass operations, and (3) pharmacological, e.g., Ozempic. (Table 3).

Our literature review focusing on human trials that assess the alleviation of back pain or reduction in the proportion of LBP patients through weight loss primarily identified studies involving surgical interventions. (Table 3) These trials typically involved either bariatric surgery, leading to fat loss through reduced food intake, or abdominoplasty, resulting in an immediate reduction in body weight and fat proportion. Both types of surgical interventions generally showed significant BMI changes in their follow-ups. These BMI changes were often associated with a reduced proportion of LBP patients or clinically significant improvements in LBP scores. Notably, the participants often involved severely obese individuals.

Contrarily, trials that promote lifestyle changes, as in requesting participants to adhere to diets, exercise regimes, and/or counselling studies, were often unable to engender significant desirable changes in patients’ weight, making assessment of back pain less valuable. Nevertheless, it is interesting to see that the lack of BMI changes did correspond with the general maintenance of pain scores and the proportion of LBP patients. There was only one study by Silişteanu et al. [220] that was able to directly report a significant correlation between the rate of BMI loss and the alleviation of pain. The direct results are not presented in Table 3, as their findings were reported separately for males and females, and rural- and urban-habituated individuals. The overall lack of BMI changes can likely be explained by two critical features: (i) the general shorter follow-up and intervention duration and (ii) the difficulty of participants to adhere and their compliance to their allocated regimes [219]. As highlighted in the interesting work of Robson et al. [221], adherence to dietary restrictions and other regimes is challenging, in particular through tele-com counselling. Given that obesity often involves complex psychological factors, including an unhealthy relationship with food and self-image, the challenges in adherence are understandable and underscore the need for compassionate and tailored interventions.

Additionally, we sought to identify clinical trials investigating the use of pharmacological interventions for managing discogenic LBP in the context of obesity; however, no studies were found testing such approaches directly. There is a rising popularity of agents like Ozempic^® (i.e., semaglutide), which have shown robust efficacy in promoting weight loss [222]. Semaglutide is a GLP-1 receptor agonist that stimulates insulin secretion, suppresses appetite, and slows gastric emptying. In a randomized controlled trial involving patients with knee osteoarthritis and obesity, once-weekly semaglutide significantly promoted weight loss and led to marked reductions in pain severity [223]. In addition to its metabolic effects, GLP-1 receptor activation has been shown to modulate inflammation and pain pathways by reducing pro-inflammatory cytokine expression, enhancing β-endorphin release, and inhibiting nociceptive signalling within the central nervous system [223,224]. However, in this trial [223], as with the relationship between obesity and LBP, the interplay between obesity and knee osteoarthritis [225] makes it difficult to fully disentangle weight-dependent effects from direct anti-inflammatory or mental-sate effects. These findings nonetheless suggest that GLP-1 receptor agonists may represent a promising dual-action therapy for obesity-related musculoskeletal pain. In conclusion, it is important to note that the current trials and studies identified are highly heterogeneous and do not uniformly investigate their impact on LBP. Furthermore, the specific sources of back pain were not consistently identified. Only one study, by Lidar et al. [110], examined spinal imaging features and reported a significant improvement in disc height with a decrease in overall BMI, suggesting that weight loss can reduce strain on the lumbar region. Additionally, most studies focused solely on recording BMI or weight changes, which can include loss of tissues other than fat. For instance, muscle loss should be avoided, as muscle strength is crucial for maintaining spinal health through supporting the spine and overall posture. We hope that more clinicians and researchers will explore this promising area further, as targeting fat loss represents potentially low-hanging fruit for developing cost-effective methods to alleviate LBP in a significant portion of the LBP patient population. Whether to recommend weight loss for LBP patients remains controversial [43,219]. While weight loss is generally safe and beneficial for overall health, though its effectiveness in treating LBP remains uncertain.

Table 3. General literature review on the effectiveness of low back pain treatment by targeting weight or fat loss.

Type	Author (Year)	Design	Intervention	N	Age (Years) Mean (±SD)	BMI (Baseline) Mean (±SD)	T2DM n (%)	LBP Rate (Baseline) n/N (%)	LBP Score (Baseline) Mean (±SD)	FU (Months)	BMI (Final FU) Mean (±SD)	LBP Rate (Final FU) n/N (%)	LBP Score (Final FU) Mean (±SD)	Imaging Findings	Comments
Surgical	McGoey (1990) [226]	Prospective single-arm	Banding	104	33.4	unspecified	unspecified	65/104 (62.5%)	-	22 (average)	unspecified	11/104 (10.6%)	-	NA	Two patients that lost weight and then regained it, had matching LBP relief and reoccurrence.
	Melissas (2003) [227]	Prospective two-arm	Banding	50	37.5 (±10.2)	46.7 (±7.7)	unspecified	29/50 (58.0%)	-	24	33.6 (±5.6)	10/50 (20.0%)	-	NA	-
	Melissas (2005) [228]	unspecified	Banding	29	37.5 (±11.2)	47.2 (±8.8)	unspecified	NA	5.5 (±2.0) *	24	32.9 (±6.3)	NA	2.1 (±1.9) *	NA	-
	Khoueir (2009) [229]	Prospective single-arm	Bypass or sleeve	38	48.4 (±10.1)	52.3 (±12.6)	unspecified	NA	5.2 (±3.4)	12	38.3 (±9.7)	NA	2.9 (±3.1)	NA	-
	Vincent (2012) [230]	Prospective two arm	Bypass or banding	25	41 (±11)	47 (±7)	unspecified	6/25 (25.0%)	5.2	3	39.1	15/25 (61.1%)	2.4	NA	Follow-up too short and lack of BMI change.
	Lidar (2012) [110]	Prospective single arm	Bypass, sleeve, or banding	30	49 (±10.4)	42.8 (±4.8)	unspecified	26/30 (86.7%)	5.7 (±3.1)	12	29.7 (±3.4)	unspecified	1.3 (±2.1)	Sign. increase L4/5-disc height (from 6.8 (±1) to 8.8 (±1) mm)	-
	Çakır (2015) [231]	Prospective single arm	Sleeve	39	37.7 (±11.3)	46.5	unspecified	unspecified	6.7 (±2.7)	6	32.3	unspecified	1.97 (±2.2)	NA	Work does not focus specifically on back pain patients
	Taylor (2018) [232]	Prospective single arm	Abdominoplasty	214	42.1 (±8.7)	26.3 (±4.3)	unspecified	195/214 (91.2%)	unspecified	6	unspecified	unspecified	unspecified	NA	Significant improvement in ODI disability scores related to LBP.
	Bhandari (2019) [233]	Prospective single arm	Bypass or Sleeve	45	54.7 (±8.5)	54.2 (±8.6)	23 (51.1%)	34/45 (75.5%)	7.3 (±1.4)	12	unspecified	25/45 (55.6%)	2.3 (±1.4)	NA	-
	Soteropulos (2020) [234]	Retrospective	Abdominoplasty	143	48	unspecified	unspecified	51/143 (35.7%)	NA	120	unspecified	unspecified	NA	NA	Improvement in ODI and SF36 scores for patients with LBP pre-operation.
	Patel (2023) [235]	Prospective single arm	Abdominoplasty	30	48.4 (±14.3)	27.8 (±4.2)	3 (10%)	21/30 (70%)	3.95	6	unspecified	unspecified	0.53	NA	-
Lifestyle/programme	Roffey (2011) [236]	Prospective single arm	Diet, exercise, and counselling	46	50.1 (±12.9)	44.7 (±7.6)	unspecified	NA	3.3 (±2.2)	12	39.6 (±8.2)	NA	2.6 (±2.5)	NA	-
	Silişteanu (2015) [220]	Prospective two arm	Diet (+physio, NSAID, analgesics, etc.)	90	unclear	unclear	unspecified	unclear	unclear	unclear	unclear	unclear	unclear	NA	Significant correlation BMI loss and VAS improvement.
	Williams (2018) [237]	RCT	Diet and exercise	79	56.0 (±13.3)	32.4 (±3.5)	unspecified	NA	6.7 (±1.8)	6	32.7 (±4.3)	NA	5.8 (±2.7)	NA	Diet was not effective in reducing BMI.
	Dunlevy (2018) [238]	Retrospective	Diet, exercise, and counselling	476	45.1 (±12.0)	50.8 (±8.1)	66 (29.3%)	281/476 (59.0%)	5.9 (±3.8)	6	47.6 (±8.0)	236/476 (49.6%)	4.5 (±3.7)	NA	-
	Safari (2020) [239]	RCT	Diet (+NSAIDs)	48	39.7 (±10.7)	28.4 (±3.5)	unspecified	NA	2.2 (±0.5)	2	unspecified	NA	1.0 (±1.0)	NA	Follow-up too short. Diet unable to result in relevant BMI loss.
	Ward (2024) [240]	Prospective single arm	Diet	136	47.7 (±10.7)	30.7 (±2.3)	Excluded	43/136 (31.8%)	unclear	3	unclear	18/136 (13.6%)	unclear	NA	-
Pharmaco- logical	None identified

* Worst pain score. Abbreviations: BMI (body mass index); LBP (low back pain); NA (not assessed/applicable); ODI ((Oswestry disability index)—a patient-reported outcome measuring the impact of disability); RCT (randomized clinical trial); sd (standard deviation); SF36 ((short form 36)—a quality-of-life patient-reported outcome survey), Sign. (significant).

Table 3. General literature review on the effectiveness of low back pain treatment by targeting weight or fat loss.

Type	Author (Year)	Design	Intervention	N	Age (Years) Mean (±SD)	BMI (Baseline) Mean (±SD)	T2DM n (%)	LBP Rate (Baseline) n/N (%)	LBP Score (Baseline) Mean (±SD)	FU (Months)	BMI (Final FU) Mean (±SD)	LBP Rate (Final FU) n/N (%)	LBP Score (Final FU) Mean (±SD)	Imaging Findings	Comments
Surgical	McGoey (1990) [226]	Prospective single-arm	Banding	104	33.4	unspecified	unspecified	65/104 (62.5%)	-	22 (average)	unspecified	11/104 (10.6%)	-	NA	Two patients that lost weight and then regained it, had matching LBP relief and reoccurrence.
	Melissas (2003) [227]	Prospective two-arm	Banding	50	37.5 (±10.2)	46.7 (±7.7)	unspecified	29/50 (58.0%)	-	24	33.6 (±5.6)	10/50 (20.0%)	-	NA	-
	Melissas (2005) [228]	unspecified	Banding	29	37.5 (±11.2)	47.2 (±8.8)	unspecified	NA	5.5 (±2.0) *	24	32.9 (±6.3)	NA	2.1 (±1.9) *	NA	-
	Khoueir (2009) [229]	Prospective single-arm	Bypass or sleeve	38	48.4 (±10.1)	52.3 (±12.6)	unspecified	NA	5.2 (±3.4)	12	38.3 (±9.7)	NA	2.9 (±3.1)	NA	-
	Vincent (2012) [230]	Prospective two arm	Bypass or banding	25	41 (±11)	47 (±7)	unspecified	6/25 (25.0%)	5.2	3	39.1	15/25 (61.1%)	2.4	NA	Follow-up too short and lack of BMI change.
	Lidar (2012) [110]	Prospective single arm	Bypass, sleeve, or banding	30	49 (±10.4)	42.8 (±4.8)	unspecified	26/30 (86.7%)	5.7 (±3.1)	12	29.7 (±3.4)	unspecified	1.3 (±2.1)	Sign. increase L4/5-disc height (from 6.8 (±1) to 8.8 (±1) mm)	-
	Çakır (2015) [231]	Prospective single arm	Sleeve	39	37.7 (±11.3)	46.5	unspecified	unspecified	6.7 (±2.7)	6	32.3	unspecified	1.97 (±2.2)	NA	Work does not focus specifically on back pain patients
	Taylor (2018) [232]	Prospective single arm	Abdominoplasty	214	42.1 (±8.7)	26.3 (±4.3)	unspecified	195/214 (91.2%)	unspecified	6	unspecified	unspecified	unspecified	NA	Significant improvement in ODI disability scores related to LBP.
	Bhandari (2019) [233]	Prospective single arm	Bypass or Sleeve	45	54.7 (±8.5)	54.2 (±8.6)	23 (51.1%)	34/45 (75.5%)	7.3 (±1.4)	12	unspecified	25/45 (55.6%)	2.3 (±1.4)	NA	-
	Soteropulos (2020) [234]	Retrospective	Abdominoplasty	143	48	unspecified	unspecified	51/143 (35.7%)	NA	120	unspecified	unspecified	NA	NA	Improvement in ODI and SF36 scores for patients with LBP pre-operation.
	Patel (2023) [235]	Prospective single arm	Abdominoplasty	30	48.4 (±14.3)	27.8 (±4.2)	3 (10%)	21/30 (70%)	3.95	6	unspecified	unspecified	0.53	NA	-
Lifestyle/programme	Roffey (2011) [236]	Prospective single arm	Diet, exercise, and counselling	46	50.1 (±12.9)	44.7 (±7.6)	unspecified	NA	3.3 (±2.2)	12	39.6 (±8.2)	NA	2.6 (±2.5)	NA	-
	Silişteanu (2015) [220]	Prospective two arm	Diet (+physio, NSAID, analgesics, etc.)	90	unclear	unclear	unspecified	unclear	unclear	unclear	unclear	unclear	unclear	NA	Significant correlation BMI loss and VAS improvement.
	Williams (2018) [237]	RCT	Diet and exercise	79	56.0 (±13.3)	32.4 (±3.5)	unspecified	NA	6.7 (±1.8)	6	32.7 (±4.3)	NA	5.8 (±2.7)	NA	Diet was not effective in reducing BMI.
	Dunlevy (2018) [238]	Retrospective	Diet, exercise, and counselling	476	45.1 (±12.0)	50.8 (±8.1)	66 (29.3%)	281/476 (59.0%)	5.9 (±3.8)	6	47.6 (±8.0)	236/476 (49.6%)	4.5 (±3.7)	NA	-
	Safari (2020) [239]	RCT	Diet (+NSAIDs)	48	39.7 (±10.7)	28.4 (±3.5)	unspecified	NA	2.2 (±0.5)	2	unspecified	NA	1.0 (±1.0)	NA	Follow-up too short. Diet unable to result in relevant BMI loss.
	Ward (2024) [240]	Prospective single arm	Diet	136	47.7 (±10.7)	30.7 (±2.3)	Excluded	43/136 (31.8%)	unclear	3	unclear	18/136 (13.6%)	unclear	NA	-
Pharmaco- logical	None identified

* Worst pain score. Abbreviations: BMI (body mass index); LBP (low back pain); NA (not assessed/applicable); ODI ((Oswestry disability index)—a patient-reported outcome measuring the impact of disability); RCT (randomized clinical trial); sd (standard deviation); SF36 ((short form 36)—a quality-of-life patient-reported outcome survey), Sign. (significant).

However, being too stringent about weight loss may discourage patients and set unrealistic expectations, particularly for those already struggling with their weight [241,242]. More research is needed to find the appropriate balance in this area.

7.2. Modulating Adipokine Signalling to Alleviate Obesity-Linked Discogenic Pain

As previously discussed, adipokines exert both systemic and local effects on spinal tissues, contributing to IDD potentially facilitating the onset or exacerbation of LBP. While targeting adipokine signalling is unlikely to resolve obesity or fully interrupt the pathological cycle described in this review, such interventions may offer benefit by dampening pain perception or reducing the catabolic effects of these factors on spinal tissues. Therapeutic strategies may include antagonizing pro-inflammatory and degradative adipokines, enhancing anti-inflammatory or protective adipokines, or modulating downstream pathways through neuro-immune or endocrine mechanisms [169]. However, given the widespread physiological roles of adipokines, such interventions require careful evaluation to avoid unintended systemic effects. Importantly, while numerous adipokine-targeting drugs are currently under investigation, a comprehensive review is beyond the scope of this review, we refer interested readers to the excellent review by Würfel et al. [243] on this specific topic.

7.3. Limitations and Considerations

This review provides a broad overview of the mechanistic connections between obesity and LBP; however, several limitations should be noted. As a scoping review, it does not aim to be exhaustive, and some relevant studies or mechanistic pathways may have been omitted. The topics and mechanisms discussed were selected based on the authors’ expertise in the field. In Section 7.1, Table 3 was reviewed as a semi-systematic search performed to identify relevant studies, involving search terms including “weight loss” and “low back pain”. Nonetheless, this should not be considered a full systematic review. Additionally, although age and sex are known to influence both obesity-related physiology and pain presentation [244,245,246,247,248,249], stratification by these factors was not feasible here due to inconsistent reporting across studies. Their role should be more carefully considered in future investigations, and we implore more work, including meta-analyses, on this topic. Finally, a common limitation in the literature is the lack of clear identification of the pain source in studies of LBP. In many cases, it remains uncertain whether the pain originates from disc, joint, musculature, or other structures, which complicates mechanistic interpretation [250]. In a similar vein, obesity severity was typically assessed using BMI alone; however, as previously mentioned, other metrics (though less practical) may offer more accurate insights. These limitations should be taken into account when interpreting the findings of this review.

8. Conclusions

Obesity significantly contributes to IDD and LBP through systemic inflammation, oxidative stress, lipid dysregulation, and metabolic disturbances, creating a catabolic environment that accelerates ECM degradation and tissue dysfunction. While the link between obesity and IDD is increasingly recognized, significant gaps in the literature persist. Most studies fail to isolate discogenic LBP, lack imaging evidence to connect fat loss with structural improvements, and overly focus on weight loss rather than fat loss. Emerging factors such as the role of plastic chemical exposure in hormone dysregulation and the influence of mental health on outcomes remain underexplored. A unified model integrating all impacted tissues, IVDs, CEPs, vertebral MAT, facet joints, and PSMs [203] is essential to fully understand this relationship. Moreover, the association between obesity, IDD, and mental health requires further study, as such psychological factors significantly influence pain perception and may impact spinal health. Strikingly, few studies have explored fat or weight loss as strategies to alleviate LBP. Future research must focus on targeted interventions, imaging-based evaluations, and the long-term effects of fat loss on IDD and LBP to guide effective, individualized treatments. Addressing these gaps is critical to mitigating the burden of obesity-related spinal disorders.