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Nutritional Approaches for Managing Obesity-Associated Metabolic Diseases
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Nutritional Approaches for Managing Obesity-Associated Metabolic Diseases

A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Nutrition and Obesity".

Deadline for manuscript submissions: 15 September 2025 | Viewed by 6571

Special Issue Editor

Dr. Neda Akhavan

E-Mail Website
Guest Editor
Department of Kinesiology and Nutrition Sciences, School of Integrated Health Sciences, University of Nevada, Las Vegas, NV 89154, USA
Interests: dietary patterns; functional foods; obesity; aging; health outcomes; functional performance

Special Issue Information

Dear Colleagues,

Obesity is a leading global health issue that contributes to the development of metabolic disorders such as type-2 diabetes, cardiovascular disease, and non-alcoholic fatty liver disease (NAFLD). These metabolic disorders share the underlying conditions and mechanisms that contribute to their development and progression, including insulin resistance, chronic inflammation, oxidative stress, hypertension, endothelial dysfunction, and dyslipidemia. For this Special Issue, we invite papers that focus on specific metabolic disorders associated with obesity, particularly Type-2 diabetes and insulin resistance, cardiovascular diseases, NAFLD, dyslipidemia, and metabolic syndrome. We encourage research that explores nutritional interventions that target these disorders, with an emphasis on personalized, sustainable dietary strategies. Diets rich in whole foods, fruits, vegetables, lean proteins, and whole grains play a vital role in managing obesity-related metabolic risk factors. Studies on the Mediterranean diet (and other healthful dietary patterns), functional foods, and nutraceuticals are welcomed, as these approaches show promise in mitigating obesity-related metabolic risks. We seek contributions that investigate the biological mechanisms connecting obesity with these metabolic disorders, as well as how dietary modifications can influence key metabolic pathways and improve associated health outcomes.

Dr. Neda Akhavan
Guest Editor

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Keywords

  • cardiometabolic disorders
  • inflammation
  • adiposity
  • dietary patterns
  • functional foods

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Published Papers (6 papers)

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Research

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15 pages, 798 KiB  
Article
Associations Between Serum Gut-Derived Tryptophan Metabolites and Cardiovascular Health Markers in Adolescents with Obesity
by Jeny E. Rivera, Renny Lan, Mario G. Ferruzzi, Elisabet Børsheim, Emir Tas and Eva C. Diaz
Nutrients 2025, 17(15), 2430; https://doi.org/10.3390/nu17152430 - 25 Jul 2025
Viewed by 176
Abstract
Background/Objectives: Gut-derived tryptophan (Trp) metabolites play important roles in metabolic and cardiovascular regulation. Although animal studies suggest their protective effects against metabolic dysfunction, data in adolescents, particularly those with obesity, remain limited. The objective of this study was to evaluate associations between circulating [...] Read more.
Background/Objectives: Gut-derived tryptophan (Trp) metabolites play important roles in metabolic and cardiovascular regulation. Although animal studies suggest their protective effects against metabolic dysfunction, data in adolescents, particularly those with obesity, remain limited. The objective of this study was to evaluate associations between circulating gut-derived Trp metabolites and markers of cardiometabolic, vascular, and platelet health in adolescents with obesity. Methods: Data were analyzed from 28 adolescents (ages 13–18; mean BMI = 36 ± 6.4 kg/m2). Fasting blood was collected to assess lipid profiles using a clinical analyzer and insulin resistance using the homeostatic model assessment for insulin resistance (HOMA-IR). Gut-derived Trp metabolites were measured by UPLC–mass spectrometry, peak oxygen uptake (VO2 peak) by gas exchange during an incremental cycle ergometer test, and body composition by dual-energy X-ray absorptiometry. Platelet spare respiratory capacity (SRC), endothelial function, and liver fat were measured using high-resolution respirometry, flow-mediated dilation (FMD) of the brachial artery, and magnetic resonance imaging respectively. Results: Indole-3-propionic acid was inversely associated with diastolic blood pressure (rho = −0.39, p = 0.047), total cholesterol (rho = −0.55, p = 0.002), and LDL-C (rho = −0.57, p = 0.0014), independent of sex and obesity severity. Indoxyl sulfate was positively correlated with fasting glucose (rho = 0.47, p = 0.012), and adolescents with impaired fasting glucose had 1.6-fold higher IS levels. Indole-3-acetaldehyde declined with age (rho = −0.50, p = 0.007), and Indole-3-acetic acid and indole were higher in Hispanics vs. non-Hispanics. No significant associations were observed between Trp metabolites and FMD, VO2 peak, or SRC. Conclusions: Gut-derived Trp metabolites, particularly indole-3-propionic and indoxyl sulfate, are associated with markers of cardiometabolic risk in adolescents with obesity. These findings support their potential relevance in early-onset cardiovascular disease risk. Full article
(This article belongs to the Special Issue Nutritional Approaches for Managing Obesity-Associated Metabolic Diseases)
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19 pages, 3780 KiB  
Article
Effects of Soy Protein on Liver and Adipose Tissue Inflammation and Gut Microbiota in Mice Fed with Ketogenic Diets
by Wen-Keng Li, I-Ting Wu, Wan-Ju Yeh, Wen-Chih Huang and Hsin-Yi Yang
Nutrients 2025, 17(15), 2428; https://doi.org/10.3390/nu17152428 - 25 Jul 2025
Viewed by 185
Abstract
Background: Studies on ketogenic diets with a higher percentage of fat composition have revealed conflicting results regarding the modulation of lipid metabolism and tissue inflammation. Furthermore, studies on soy protein consumption in ketogenic diets remain limited. In this study, the effects of [...] Read more.
Background: Studies on ketogenic diets with a higher percentage of fat composition have revealed conflicting results regarding the modulation of lipid metabolism and tissue inflammation. Furthermore, studies on soy protein consumption in ketogenic diets remain limited. In this study, the effects of ketogenic diets on hepatic and adipose tissue inflammation and of soy protein replacement in ketogenic diets were investigated. Methods: Mice were randomly assigned to a control diet (C), ketogenic diet (KD), or ketogenic with soy protein (KS) groups for an 18-week experiment. Both ketogenic diet groups were fed a low-carbohydrate, high-fat diet during the first 12 weeks and a ketogenic diet during the last 6 weeks of the experiment. The KS group was fed the same diet as the KD group, but soy protein was substituted for casein during the last 6 weeks. Results: The KD and KS groups exhibited higher plasma β-hydroxybutyrate levels; a higher incidence of hyperlipidemia; and lower blood glucose, mesenteric fat mass, adipose tissue TNF-α, IL-1β levels, and NLRP3 protein expression compared with the C group. In the gut microbiota analysis, the KD group had a higher F-B ratio than the C group. Greater A. muciniphila abundance and a lower F-B ratio were noted in the KS group compared with the KD group. Conclusions: Although ketogenic diets decreased mesenteric fat mass and adipose tissue inflammation and modulated NLRP3 expression, they were associated with hepatic inflammation and gut dysbiosis. Soy protein consumption in a ketogenic diet did not differ from casein consumption regarding diet-induced tissue inflammation, but it may have altered the gut microbiota. Full article
(This article belongs to the Special Issue Nutritional Approaches for Managing Obesity-Associated Metabolic Diseases)
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17 pages, 1274 KiB  
Article
Low-Calorie, High-Protein Ketogenic Diet Versus Low-Calorie, Low-Sodium, and High-Potassium Mediterranean Diet in Overweight Patients and Patients with Obesity with High-Normal Blood Pressure or Grade I Hypertension: The Keto–Salt Pilot Study
by Matteo Landolfo, Lucia Stella, Alessandro Gezzi, Francesco Spannella, Paolo Turri, Lucia Sabbatini, Sofia Cecchi, Beatrice Lucchetti, Massimiliano Petrelli and Riccardo Sarzani
Nutrients 2025, 17(10), 1739; https://doi.org/10.3390/nu17101739 - 20 May 2025
Cited by 1 | Viewed by 2749
Abstract
Background and Objective: Dietary interventions are the first-line treatment for overweight individuals (OW) and individuals with obesity (OB) with high-normal blood pressure (BP) or grade I hypertension, especially when at low-to-moderate cardiovascular risk (CVR). However, current guidelines do not specify the most effective [...] Read more.
Background and Objective: Dietary interventions are the first-line treatment for overweight individuals (OW) and individuals with obesity (OB) with high-normal blood pressure (BP) or grade I hypertension, especially when at low-to-moderate cardiovascular risk (CVR). However, current guidelines do not specify the most effective dietary approach for optimising cardiovascular and metabolic outcomes in this population. This study aimed to compare the effects of a low-calorie, high-protein ketogenic diet (KD) vs. a low-calorie, low-sodium, and high-potassium Mediterranean diet (MD) on BP profiles assessed via ambulatory BP monitoring (ABPM), as well as on anthropometric measures, metabolic biomarkers, and body composition evaluated by bioelectrical impedance analysis (BIA). Methods: This prospective observational bicentric pilot study included 26 non-diabetic adult outpatients with central OW status or OB status (body mass index, BMI > 27 kg/m2) and high-normal BP (≥130/85 mmHg) or grade I hypertension (140–160/90–100 mmHg), based on office BP measurements. All participants had low-to-moderate CVR according to the second version of the systemic coronary risk estimation (SCORE2) and were selected and categorized as either KD (n = 15) or MD (n = 11). Comprehensive blood analysis, BIA, and ABPM were conducted at baseline and after three months. Results: At baseline, no significant differences were observed between the groups. Following three months of dietary intervention, both groups exhibited substantial reductions in body weight (KD: 98.6 ± 13.0 to 87.3 ± 13.4 kg; MD: 93.8 ± 17.7 to 86.1 ± 19.3 kg, p < 0.001) and waist circumference. Mean 24 h systolic BP (SBP) and diastolic BP (DBP) significantly declined in both groups (24 h mean SBP decreased from 125.0 ± 11.3 to 116.1 ± 8.5 mmHg (p = 0.003) and 24 h mean DBP decreased from 79.0 ± 8.4 to 73.7 ± 6.4 mmHg (p < 0.001)). Fat-free mass (FFM) increased, whereas fat mass (FM), blood lipid levels, and insulin concentrations decreased significantly. The ΔFM/ΔFFM correlates with ABP improvements. However, no significant between-group differences were detected at follow-up. Conclusions: The KD and the MD mediated weight loss and body composition changes, effectively improving bio-anthropometric and cardiovascular parameters in individuals with OW status or OB status and high BP. Although more extensive studies are warranted to elucidate potential long-term differences, our findings suggest the manner in which these two different popular dietary approaches may equally confer metabolic and cardiovascular benefits, emphasising the importance of weight and FM loss. Full article
(This article belongs to the Special Issue Nutritional Approaches for Managing Obesity-Associated Metabolic Diseases)
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17 pages, 5043 KiB  
Article
Cannabigerol Alleviates Liver Damage in Metabolic Dysfunction-Associated Steatohepatitis Female Mice via Inhibition of Transforming Growth Factor Beta 1
by Raznin Joly, Fariha Tasnim, Kelsey Krutsinger, Zhuorui Li, Nicholas A. Pullen and Yuyan Han
Nutrients 2025, 17(9), 1524; https://doi.org/10.3390/nu17091524 - 30 Apr 2025
Viewed by 591
Abstract
Background and Aims: Metabolic dysfunction-associated steatohepatitis (MASH), a progressive form of metabolic dysfunction-associated steatotic liver disease (MASLD), involves inflammation, fibrosis, steatosis, and oxidative stress. Previous research from our lab shows that cannabigerol (CBG) reduces inflammation and fibrosis in male MASH mice, but its [...] Read more.
Background and Aims: Metabolic dysfunction-associated steatohepatitis (MASH), a progressive form of metabolic dysfunction-associated steatotic liver disease (MASLD), involves inflammation, fibrosis, steatosis, and oxidative stress. Previous research from our lab shows that cannabigerol (CBG) reduces inflammation and fibrosis in male MASH mice, but its effects in females remain unknown. Given immune cell population changes in MASLD patients, this study examines CBG’s impact on methionine-choline deficient (MCD) diet-induced MASH in female mice. Methods: MCD-fed female mice are supplemented with two different doses for three weeks. Liver fibrosis, steatosis, oxidative stress, ductular reaction, and inflammation are assessed via Sirius Red, Oil Red O, immunohistochemistry, and immunofluorescence staining. Immune cell changes in non-parenchymal cells (NPCs) are analyzed via flow cytometry. Results: CBG treatment improves liver health by reducing leukocyte infiltration. Both CBG doses significantly decrease fibrosis, oxidative stress, ductular proliferation, and inflammation in MCD-fed mice, including monocyte and T lymphocyte reductions. Additionally, CBG downregulates mast cell activation, inhibiting transforming growth factor (TGF)-β1 release, thereby suppressing hepatic stellate cell activation. This reduces collagen deposition, fibrosis, and ductular proliferation. Conclusions: Our findings provide insights for pre-clinical and clinical research, highlighting CBG’s potential therapeutic role and dosage considerations in mitigating liver fibrosis and inflammation in female patients. Full article
(This article belongs to the Special Issue Nutritional Approaches for Managing Obesity-Associated Metabolic Diseases)
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Review

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25 pages, 1591 KiB  
Review
Cardiovascular Risk Factors, Alzheimer’s Disease, and the MIND Diet: A Narrative Review from Molecular Mechanisms to Clinical Outcomes
by Amirhossein Ataei Kachouei, Saiful Singar, Amber Wood, Jason D. Flatt, Sara K. Rosenkranz, Richard R. Rosenkranz and Neda S. Akhavan
Nutrients 2025, 17(14), 2328; https://doi.org/10.3390/nu17142328 - 16 Jul 2025
Viewed by 537
Abstract
Cardiovascular diseases (CVDs) and Alzheimer’s disease (AD) are among the top 10 causes of death worldwide. Accumulating evidence suggests connections between CVD risk factors―including hypertension (HTN), hyperlipidemia (HLP), diabetes mellitus (DM), obesity, and physical inactivity―and AD. The Mediterranean–DASH Intervention for Neurodegenerative Delay (MIND) [...] Read more.
Cardiovascular diseases (CVDs) and Alzheimer’s disease (AD) are among the top 10 causes of death worldwide. Accumulating evidence suggests connections between CVD risk factors―including hypertension (HTN), hyperlipidemia (HLP), diabetes mellitus (DM), obesity, and physical inactivity―and AD. The Mediterranean–DASH Intervention for Neurodegenerative Delay (MIND) dietary pattern has recently garnered considerable attention as a key preventive strategy for both CVDs and AD. While previous studies have examined the connections between CVD risk factors and AD, they have not thoroughly explored their underlying mechanisms. Therefore, the current literature review aims to synthesize the literature and highlight underlying mechanisms from preclinical to clinical studies to elucidate the relationship between CVD risk factors, AD, and the role of the MIND dietary pattern in these conditions. The MIND dietary pattern emphasizes foods rich in antioxidants and brain-healthy nutrients such as vitamin E, folate, polyphenols, flavonoids, carotenoids, fiber, monounsaturated fatty acids, and omega-3 fatty acids. These components have been associated with reduced amyloid-β accumulation in preclinical studies and may contribute to the prevention of AD, either directly or indirectly by affecting CVD risk factors. Despite the extensive evidence from preclinical and observational studies, few clinical trials have investigated the effects of the MIND dietary pattern on cognitive health. Therefore, long-term clinical trials are required to better understand and establish the potential role of the MIND dietary pattern in preventing and managing AD. Full article
(This article belongs to the Special Issue Nutritional Approaches for Managing Obesity-Associated Metabolic Diseases)
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28 pages, 819 KiB  
Review
Chrononutrition and Energy Balance: How Meal Timing and Circadian Rhythms Shape Weight Regulation and Metabolic Health
by Claudia Reytor-González, Daniel Simancas-Racines, Náthaly Mercedes Román-Galeano, Giuseppe Annunziata, Martina Galasso, Raynier Zambrano-Villacres, Ludovica Verde, Giovanna Muscogiuri, Evelyn Frias-Toral and Luigi Barrea
Nutrients 2025, 17(13), 2135; https://doi.org/10.3390/nu17132135 - 27 Jun 2025
Viewed by 1962
Abstract
Obesity and metabolic disorders remain major global health concerns, traditionally attributed to excessive caloric intake and poor diet quality. Recent studies emphasize that the timing of meals plays a crucial role in determining metabolic health. This review explores chrononutrition, a growing field that [...] Read more.
Obesity and metabolic disorders remain major global health concerns, traditionally attributed to excessive caloric intake and poor diet quality. Recent studies emphasize that the timing of meals plays a crucial role in determining metabolic health. This review explores chrononutrition, a growing field that examines how food intake patterns interact with endogenous circadian rhythms to influence energy balance, glucose and lipid metabolism, and cardiometabolic risk. The circadian system, which includes a central clock in the suprachiasmatic nucleus and peripheral clocks in metabolic tissues, regulates physiological functions on a 24 h cycle. While light entrains the central clock, feeding schedules act as key synchronizers for peripheral clocks. Disrupting this alignment—common in modern lifestyles involving shift work or late-night eating—can impair hormonal rhythms, reduce insulin sensitivity, and promote adiposity. Evidence from clinical and preclinical studies suggests that early time-restricted eating, where food intake is confined to the morning or early afternoon, offers significant benefits for weight control, glycemic regulation, lipid profiles, and mitochondrial efficiency, even in the absence of caloric restriction. These effects are particularly relevant for populations vulnerable to circadian disruption, such as adolescents, older adults, and night-shift workers. In conclusion, aligning food intake with circadian biology represents a promising, low-cost, and modifiable strategy to improve metabolic outcomes. Integrating chrononutrition into clinical and public health strategies may enhance dietary adherence and treatment efficacy. Future large-scale studies are needed to define optimal eating windows, assess long-term sustainability, and establish population-specific chrononutritional guidelines. Full article
(This article belongs to the Special Issue Nutritional Approaches for Managing Obesity-Associated Metabolic Diseases)
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