International Journal of Molecular Sciences

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20 pages, 4675 KB

Open AccessArticle

MyD88 Inhibition Ameliorates Diabetes-Induced Hepatic Inflammation and Gluconeogenesis Through Adipose IL-10 Induction

by Yi-Cheng Li, Hsiao-Chi Lai, Pei-Hsuan Chen, Chia-Hua Tang and Lee-Wei Chen

Int. J. Mol. Sci. 2026, 27(6), 2883; https://doi.org/10.3390/ijms27062883 - 23 Mar 2026

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Abstract

Myeloid differentiation factor 88 (MyD88) signaling plays a central role in inflammatory pathway activation. Adipose-derived interleukin-10 (IL-10), which is induced by insulin and lipopolysaccharides, suppresses hepatic glucose production. This study investigated the role of MyD88/IL-10 signaling in diabetes-induced systemic inflammation and hepatic gluconeogenesis. [...] Read more.

Myeloid differentiation factor 88 (MyD88) signaling plays a central role in inflammatory pathway activation. Adipose-derived interleukin-10 (IL-10), which is induced by insulin and lipopolysaccharides, suppresses hepatic glucose production. This study investigated the role of MyD88/IL-10 signaling in diabetes-induced systemic inflammation and hepatic gluconeogenesis. Stromal vascular fractions (SVFs) were isolated from the adipose tissue of Lepr^db^/db and Lepr^db^/dbMyD88^−/− mice and treated with IL-10 followed by analysis of inflammatory cytokine expression. IL-10 (10 or 50 ng) was injected into adipose tissue of type 2 DM (T2DM) (Lepr^db^/db) mice to investigate its effect on blood dipeptidyl peptidase-4 (DPP4) activity, insulin resistance, and hepatic gluconeogenic signaling. Hepatic inflammatory markers, gluconeogenic gene expression, and metabolic parameters were assessed. Compared with wild-type mice, Lepr^db^/db mice exhibited significantly reduced FOXP3 protein expression and IL-10 levels in adipose tissue, accompanied by increased blood DPP4 activity and adiponectin levels, elevated hepatic inflammatory cytokines, and increased G6pc and Pck1 mRNA expression. In contrast, Lepr^db^/dbMyD88^−/− mice showed increased Foxp3 protein and PDGFα mRNA expression, decreased IL-6 and CCL2 mRNA expression in SVFs, increased IL-10 levels in adipose tissue, and lower blood adiponectin and ALT levels. MyD88 deletion also attenuated Kupffer cell accumulation, hepatic inflammatory cytokine expression, and gluconeogenic gene expression. In vitro, IL-10 treatment of SVFs from Lepr^db^/db mice significantly reduced IL-6 and CCL2 expression and increased Foxp3 mRNA expression. In vivo, adipose IL-10 injection increased Foxp3 and IL-10 expression, expanded Treg cells in SVFs, and activated hepatic Akt signaling, while suppressing pJNK and pNF-κB signaling. These changes were accompanied by reduced blood DPP4 activity, ALT and adiponectin levels, decreased Kupffer cell-derived inflammatory cytokines, reduced hepatic G6pc and Pck1 expression, and improved glucose tolerance. MyD88 signaling induces adipose IL-6 and CCL2, liver inflammation and gluconeogenesis, and blood DPP4 activity by reducing IL-10 and Foxp3 of adipose tissue in T2DM. Enhancing adipose IL-10 induces Treg expansion, inhibits JNK and NF-κB signaling, and alleviates hepatic gluconeogenesis and insulin resistance. MyD88 inhibition or IL-10 elevation in adipose tissue may represent a novel strategy for metabolic syndrome. Full article

(This article belongs to the Special Issue Molecular Research in Obesity and Obesity Related Disorders: 3rd Edition)

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23 pages, 845 KB

Open AccessArticle

Anti-Atherogenic Activities of Exopolysaccharides and Their Producing Strain Limosilactobacillus fermentum MC1 in Mice

by Nada Oršolić, Barbara Toljanić, Dyana Odeh, Nina Čuljak, Kate Šešelja, Mirela Baus Lončar, Domagoj Đikić, Andreja Leboš Pavunc and Blaženka Kos

Int. J. Mol. Sci. 2026, 27(5), 2473; https://doi.org/10.3390/ijms27052473 - 7 Mar 2026

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Abstract

Atherosclerosis, the leading cause of death worldwide, is a chronic inflammatory disease leading to the accumulation of lipid-rich plaques within the artery wall. Accumulating evidence indicates that intestinal microbiota plays an important regulatory role in atherosclerosis at all stages of the disease. Through [...] Read more.

Atherosclerosis, the leading cause of death worldwide, is a chronic inflammatory disease leading to the accumulation of lipid-rich plaques within the artery wall. Accumulating evidence indicates that intestinal microbiota plays an important regulatory role in atherosclerosis at all stages of the disease. Through numerous metabolites, the intestinal microbiota can regulate immune and inflammatory cells and their mediators, as well as lipid metabolism, thereby contributing to the development and progression of atherosclerosis. With these assumptions in mind, we investigated the possibility of using Limosilactobacillus fermentum MC1 (L. fermentum MC1) and its exopolysaccharides (EPSs) in the reduction of lipid and atherogenic parameters as a preventive strategy in preventing the occurrence of cardiovascular diseases (CVD). We investigated the effect of L. fermentum MC1 and its EPSs on the health status of mice by monitoring the following parameters: body weight, colon length and weight, relative weight of organs, hematological (Hgb, WBC, number of erythrocytes, MCHC, MCV, MCH), and biochemical blood parameters including glucose, serum enzymes (ALT, ALP, amylase), urea, creatinine and lipid profile (total cholesterol, triglycerides, HDL, VLDL, LDL), different atherogenic parameters, blood biomarkers such as lymphocyte-to-monocyte (LMR) and neutrophil-to-lymphocyte (NLR) ratios, molecular inflammatory markers (IL1β, IL6, MCP1, IL1α, TLR4, TNFα, CD68, TGFβ), apoptosis markers (BCL2, AIFM1, IGF-1R), and endoplasmic reticulum stress markers (CHOP and GRP94) as well as oxidative stress (NOX2) markers in the colon. Furthermore, the level of lipid peroxidation, nitric oxide and glutathione concentrations in the liver, kidneys and spleen were measured. L. fermentum MC1 and its EPSs may prevent the development of atherosclerosis and the progression of CVD through antioxidant, anti-inflammatory, immunomodulatory activities, and regulation of the gut microbiome and lipid metabolism. The observed reduction in lipid and atherogenic determinants suggests that L. fermentum MC1 and its EPSs may contribute to atheroprotection and confer multiple health benefits. Full article

(This article belongs to the Special Issue Molecular Research in Obesity and Obesity Related Disorders: 3rd Edition)

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12 pages, 1714 KB

Open AccessArticle

Dnmt3b Deficiency in Adipocyte Progenitor Cells Ameliorates Obesity in Female Mice

by Yifei Huang, Sean Yu, Qiang Cao, Weiqing Tang, Jia Jing, Bingzhong Xue and Hang Shi

Int. J. Mol. Sci. 2026, 27(2), 861; https://doi.org/10.3390/ijms27020861 - 15 Jan 2026

Cited by 1 | Viewed by 537

Abstract

Obesity arises from chronic energy imbalance, where energy intake exceeds energy expenditure. Emerging evidence supports a key role of DNA methylation in the regulation of adipose tissue development and metabolism. We have recently discovered a key role of DNA methylation, catalyzed by DNA [...] Read more.

Obesity arises from chronic energy imbalance, where energy intake exceeds energy expenditure. Emerging evidence supports a key role of DNA methylation in the regulation of adipose tissue development and metabolism. We have recently discovered a key role of DNA methylation, catalyzed by DNA methyltransferase 1 or 3a (Dnmt1 or 3a), in the regulation of adipocyte differentiation and metabolism. Here, we aimed to investigate the role of adipose progenitor cell Dnmt3b—an enzyme mediating de novo DNA methylation—in energy metabolism and obesity. We generated a genetic model with Dnmt3b knockout in adipocyte progenitor cells (PD3bKO) by crossing Dnmt3b floxed mice with Platelet-derived growth factor receptor alpha (PDGFRα) Cre mice. Dnmt3b deletion in adipocyte progenitors enhanced thermogenic gene expression in brown adipose tissue, increased overall energy expenditure, and mitigated high-fat diet (HFD)-induced obesity in female mice. PD3bKO mice also displayed a lower respiratory exchange ratio (RER), indicative of a metabolic shift favoring fat utilization as an energy source. Furthermore, female PD3bKO mice exhibited improved insulin sensitivity alongside their lean phenotype. In contrast, male PD3bKO mice showed no changes in body weight but demonstrated decreased insulin sensitivity, revealing a sexually dimorphic metabolic response to Dnmt3b deletion in adipose progenitor cells. These findings underscore the critical role of Dnmt3b in regulating energy homeostasis, body weight, and metabolic health, with significant implications for understanding sex-specific mechanisms of obesity and metabolism. Full article

(This article belongs to the Special Issue Molecular Research in Obesity and Obesity Related Disorders: 3rd Edition)

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20 pages, 3691 KB

Open AccessArticle

Dysregulation of the FGF21–Adiponectin Axis in a Large Cohort of Patients with Severe Obesity and Liver Disease

by Helena Castañé, Andrea Jiménez-Franco, Alina-Iuliana Onoiu, Vicente Cambra-Cortés, Anna Hernández-Aguilera, David Parada, Francesc Riu, Antonio Zorzano, Jordi Camps and Jorge Joven

Int. J. Mol. Sci. 2025, 26(17), 8510; https://doi.org/10.3390/ijms26178510 - 2 Sep 2025

Cited by 2 | Viewed by 2379

Abstract

We investigated the impact of liver damage on systemic inter-organ communication in an extensive observational case–control study of 923 patients with severe obesity and biopsy-confirmed metabolic dysfunction-associated steatotic liver disease (MASLD) or metabolic dysfunction-associated steatohepatitis (MASH) undergoing bariatric surgery. Using a comprehensive panel [...] Read more.

We investigated the impact of liver damage on systemic inter-organ communication in an extensive observational case–control study of 923 patients with severe obesity and biopsy-confirmed metabolic dysfunction-associated steatotic liver disease (MASLD) or metabolic dysfunction-associated steatohepatitis (MASH) undergoing bariatric surgery. Using a comprehensive panel of circulating organokines, including fibroblast growth factor (FGF) 19, FGF21, adiponectin, galectin-3, irisin, and leptin, along with choline metabolites, we characterized metabolic signaling patterns associated with liver disease severity. Compared to controls, patients with MASLD/MASH exhibited significantly lower levels of FGF19, choline, and trimethylamine, while FGF21, galectin-3, irisin, and leptin were elevated. Sex-specific alterations in leptin and adiponectin were observed in patients with severe obesity but not in controls. Network analysis revealed a complex and individualized interplay among organokines, shaped by age, sex, and anthropometric factors. Despite this complexity, a dysregulation of the FGF21–adiponectin axis was associated with more advanced liver involvement. The large cohort and comprehensive organokine profiling studied provide valuable insights into the role of the FGF21–adiponectin axis on systemic metabolic alterations in severe obesity and their potential clinical implications. Full article

(This article belongs to the Special Issue Molecular Research in Obesity and Obesity Related Disorders: 3rd Edition)

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15 pages, 2372 KB

Open AccessArticle

Geniposide Mitigates Insulin Resistance and Hepatic Fibrosis via Insulin Signaling Pathway

by Seung-Hyun Oh, Min-Seong Lee and Byung-Cheol Lee

Int. J. Mol. Sci. 2025, 26(16), 8079; https://doi.org/10.3390/ijms26168079 - 21 Aug 2025

Cited by 3 | Viewed by 2014

Abstract

Insulin resistance is a key driver of metabolic disorders, including type 2 diabetes and non-alcoholic fatty liver disease (NAFLD), progressing to non-alcoholic steatohepatitis (NASH). This study investigated the effects of geniposide (GP) on insulin sensitivity and hepatic fibrosis in a high-fat diet (HFD)-induced [...] Read more.

Insulin resistance is a key driver of metabolic disorders, including type 2 diabetes and non-alcoholic fatty liver disease (NAFLD), progressing to non-alcoholic steatohepatitis (NASH). This study investigated the effects of geniposide (GP) on insulin sensitivity and hepatic fibrosis in a high-fat diet (HFD)-induced NASH model. C57BL/6 mice were fed an HFD for five weeks and subsequently divided into normal chow (NC), HFD, HFD with GP 50 mg/kg (GP50), and HFD with GP 100 mg/kg (GP100) groups. The treatments were administered orally for 12 weeks. GP treatment significantly reduced body weight as well as epididymal fat and liver weights, while no differences were observed in food intake. Improvements in glucose and lipid metabolism were observed in oral glucose tolerance tests, homeostatic model assessment of insulin resistance (HOMA-IR), and blood lipid profiles. Histological analyses revealed that GP suppressed adipocyte hypertrophy and hepatic lipid accumulation and hepatic fibrosis. To further elucidate molecular mechanisms of GP, quantitative real-time polymerase chain reaction (qRT-PCR) analysis was conducted in the liver tissue. GP downregulated expression of inflammatory markers, including F4/80, tumor necrosis factor (TNF)-α, and interleukin (IL)-6. GP treatment modulated genes involved in insulin signaling including Janus kinase 2 (JAK2), insulin receptor (INSR), insulin receptor substrate 2 (IRS-2), and protein kinase B (AKT1) gene expression levels. This suggests GP suppresses inflammation and mitigates insulin resistance by activating the INSR–IRS2–Akt pathway. Additionally, GP enhanced adenosine monophosphate-activated protein kinase (AMPK) expression, suggesting its potential role in improving glucose and lipid metabolism. In conclusion, GP improves insulin resistance, inflammation, and hepatic fibrosis, highlighting its therapeutic potential for NASH and related metabolic disorders. Full article

(This article belongs to the Special Issue Molecular Research in Obesity and Obesity Related Disorders: 3rd Edition)

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13 pages, 269 KB

Open AccessArticle

Association of Genetically Predicted Activity of AMP Deaminase 1 with Clinical and Biochemical Parameters in Diabetic Individuals with Coronary Artery Disease

by Maria Pietrzak-Nowacka, Ewa Gątarska, Krzysztof Safranow, Agnieszka Boroń, Kazimierz Ciechanowski, Jeremy S. C. Clark, Andrzej Ciechanowicz and Dorota Kostrzewa-Nowak

Int. J. Mol. Sci. 2025, 26(16), 8071; https://doi.org/10.3390/ijms26168071 - 21 Aug 2025

Viewed by 1487

Abstract

Some reports indicated the association of rs17602729 and rs34526199 functional polymorphisms of the AMPD1 gene encoding adenosine monophosphate deaminase 1 (AMPD1) with the risk of coronary artery disease (CAD) and/or its intermediate phenotype. Therefore, the aim of our study was to analyze the [...] Read more.

Some reports indicated the association of rs17602729 and rs34526199 functional polymorphisms of the AMPD1 gene encoding adenosine monophosphate deaminase 1 (AMPD1) with the risk of coronary artery disease (CAD) and/or its intermediate phenotype. Therefore, the aim of our study was to analyze the association of both AMPD1 polymorphisms with the predisposition to disease and both clinical and biochemical phenotypes but solely in diabetic individuals with CAD. The study group consisted of 196 adult diabetic individuals with CAD, and the control group comprised 200 healthy newborns. Both AMPD1 polymorphisms were identified by a SNaPshot minisequencing reaction. Clinical and laboratory data were taken from patients’ records. There were no significant differences between both groups in the frequency distributions of AMPD1:rs17602729 and rs34526199 alleles or genotypes. BMI and the frequency of obesity in TT rs17602729 homozygotes (no AMPD1 activity) were significantly lower and the serum concentration of HDL cholesterol was significantly higher compared to other patients. The concentrations of total cholesterol and LDL cholesterol in homozygotes for wild-type AMPD1:rs17602729 (c.34C) and rs34526199 (c.860A) alleles (full AMPD1 activity) were significantly lower compared to its values in other patients. Our results suggest that genetically predicted activity of AMPD1 is associated with variation in body mass and lipid metabolism in diabetic Polish people with CAD. Full article

(This article belongs to the Special Issue Molecular Research in Obesity and Obesity Related Disorders: 3rd Edition)

Review

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12 pages, 565 KB

Open AccessReview

Metabolic Benefits vs. Cardiovascular Uncertainty: A Critical Review of GLP-1 Receptor Agonists in Type 1 Diabetes

by Elżbieta Wójcik-Sosnowska, Adrianna Tabeau, Agnieszka Pawlik, Bartłomiej Węglarz and Leszek Czupryniak

Int. J. Mol. Sci. 2026, 27(9), 3882; https://doi.org/10.3390/ijms27093882 - 27 Apr 2026

Viewed by 162

Abstract

Type 1 diabetes (T1DM) is associated with elevated cardiovascular (CV) risk, often exacerbated by the rising prevalence of obesity. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) reduce CV risk in type 2 diabetes, but their role in T1DM is less well-defined. This umbrella review [...] Read more.

Type 1 diabetes (T1DM) is associated with elevated cardiovascular (CV) risk, often exacerbated by the rising prevalence of obesity. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) reduce CV risk in type 2 diabetes, but their role in T1DM is less well-defined. This umbrella review synthesizes evidence from systematic reviews, meta-analyses, and Mendelian Randomization (MR) studies to evaluate the metabolic efficacy and safety of GLP-1 RAs in T1DM. Adjunctive therapy, particularly with liraglutide and exenatide, was associated with clinically meaningful weight reduction (mean difference: −4.35 kg to −5.1 kg) and lower total daily insulin doses. HbA1c reductions were statistically significant but modest (0.2–0.3%), with no improvement in Time in Range. Secondary benefits included lower systolic blood pressure. Safety data were mixed: the risk of severe hypoglycemia was not increased, whereas Time Below Range and gastrointestinal adverse events were more frequent. Evidence on diabetic ketoacidosis (DKA) was inconsistent across studies. Overall, GLP-1 RAs improve weight and reduce insulin requirements in T1DM, potentially mitigating indirect CV risk factors; however their direct cardiovascular benefits remain unproven in the absence of dedicated outcome trials. Full article

(This article belongs to the Special Issue Molecular Research in Obesity and Obesity Related Disorders: 3rd Edition)

25 pages, 622 KB

Open AccessReview

Extracellular Vesicles in Obesity: From Pathophysiological Mediators to Therapeutic Tools

by Nikola Pavlović, Petar Todorović, Mirko Maglica, Andrea Kopilaš, Roko Šantić, Marko Kumrić, Marino Lukenda and Joško Božić

Int. J. Mol. Sci. 2026, 27(7), 3137; https://doi.org/10.3390/ijms27073137 - 30 Mar 2026

Viewed by 671

Abstract

Obesity is increasingly recognized as a disease of dysregulated intercellular communication rather than merely an energy imbalance. Extracellular vesicles (EVs), membrane-bound nanoparticles (30–1000 nm) released by nearly all cell types, act as central mediators of this pathological crosstalk. In obesity, hypertrophic adipocytes, pro-inflammatory [...] Read more.

Obesity is increasingly recognized as a disease of dysregulated intercellular communication rather than merely an energy imbalance. Extracellular vesicles (EVs), membrane-bound nanoparticles (30–1000 nm) released by nearly all cell types, act as central mediators of this pathological crosstalk. In obesity, hypertrophic adipocytes, pro-inflammatory macrophages, and dysfunctional endothelial cells secrete EVs carrying altered cargo, including pro-inflammatory miRNAs (e.g., miR-34a, miR-155), bioactive lipids, and stress proteins, which propagate systemic metabolic dysfunction. Adipose tissue-derived EVs impair hepatic fatty acid oxidation, promote steatohepatitis, suppress pancreatic beta-cell insulin secretion, induce skeletal muscle insulin resistance via PPARγ repression, and contribute to endothelial dysfunction and atherosclerosis. EV-mediated adipocyte–macrophage crosstalk reinforces chronic adipose inflammation. Circulating EVs also provide biomarkers: subpopulation ratios, miRNA signatures, and tissue factor-positive EVs reflect disease severity, predict cardiovascular risk, and monitor therapeutic responses, with machine learning enhancing diagnostic precision. Therapeutically, EVs from mesenchymal stem cells, Wharton’s jelly MSCs, adipose progenitors, and M2 macrophages reverse insulin resistance, hepatic steatosis, and adipose inflammation in preclinical models. Engineering strategies improve EV potency and tissue targeting, and Phase I trials confirm safety, though manufacturing and cost remain barriers. Preclinical and early clinical studies of MSC-EVs confirm a favorable safety profile, though manufacturing scalability and cost remain barriers to widespread clinical adoption. Overall, EVs represent both diagnostic tools and therapeutic vehicles in precision obesity medicine, offering a pathway from symptom management toward true disease remission. Full article

(This article belongs to the Special Issue Molecular Research in Obesity and Obesity Related Disorders: 3rd Edition)

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13 pages, 637 KB

Open AccessReview

Myostatin in Obesity: A Molecular Link Between Metabolic Dysfunction and Musculotendinous Remodeling

by Leonardo Cesanelli, Petras Minderis, Andrej Fokin, Aivaras Ratkevicius, Danguole Satkunskiene and Hans Degens

Int. J. Mol. Sci. 2026, 27(2), 967; https://doi.org/10.3390/ijms27020967 - 18 Jan 2026

Cited by 2 | Viewed by 1019

Abstract

Obesity is increasingly recognized not only as a metabolic disorder but also as a condition marked by the structural and functional deterioration of skeletal muscle and tendon tissues. Central to this process is the dysregulation of the extracellular matrix (ECM) resulting in fibrosis [...] Read more.

Obesity is increasingly recognized not only as a metabolic disorder but also as a condition marked by the structural and functional deterioration of skeletal muscle and tendon tissues. Central to this process is the dysregulation of the extracellular matrix (ECM) resulting in fibrosis and ectopic fat accumulation, factors that contribute to impaired tissue mechanics. Myostatin (GDF-8), a member of the TGF-β superfamily, is known as a negative regulator of muscle mass. It can also mediate interaction between adipose and other tissues including muscles and tendons. In obesity, elevated myostatin levels have been reported to be associated with insulin resistance, muscle atrophy, and activation of SMAD2/3 signaling, while experimental and preclinical studies indicate that myostatin inhibition can improve glucose homeostasis and increase lean mass. Emerging evidence suggests that myostatin also plays a critical role in muscle ECM and tendon remodeling. Restoring its physiological levels may help reverse ECM disorganization and reduce tissue fragility associated with musculotendinous dysfunction. This review highlights the multifaceted role of myostatin in obesity, beyond its role in muscle catabolism, to include modulation of structural integrity, metabolism, and mechanical adaptability of the musculotendinous system. Understanding how myostatin responds to metabolic stress and affects biomechanical remodeling offers novel insights into obesity-related muscle and tendon dysfunction. Full article

(This article belongs to the Special Issue Molecular Research in Obesity and Obesity Related Disorders: 3rd Edition)

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56 pages, 2536 KB

Open AccessReview

Metaflammation’s Role in Systemic Dysfunction in Obesity: A Comprehensive Review

by Ioana-Maria Crasan, Matei Tanase, Corina Elena Delia, Gratiela Gradisteanu-Pircalabioru, Anisoara Cimpean and Elena Ionica

Int. J. Mol. Sci. 2025, 26(21), 10445; https://doi.org/10.3390/ijms262110445 - 27 Oct 2025

Cited by 9 | Viewed by 9929

Abstract

Obesity is redefined as a complex systemic disease, transcending mere caloric imbalance, driven by intricate dysregulation across metabolic, neuroendocrine, immunological, and epigenetic axes. Central to its pathology is adipose tissue, which is considered a dynamic endocrine and immune organ. Its dysfunctional expansion fuels [...] Read more.

Obesity is redefined as a complex systemic disease, transcending mere caloric imbalance, driven by intricate dysregulation across metabolic, neuroendocrine, immunological, and epigenetic axes. Central to its pathology is adipose tissue, which is considered a dynamic endocrine and immune organ. Its dysfunctional expansion fuels chronic, low-grade systemic inflammation, termed “metaflammation”, characterised by pathways such as NF-kB and NLRP3 inflammasome activation, as well as pervasive immune cell infiltration. This inflammatory state could profoundly impair insulin signalling and contribute to major complications, including insulin resistance, type 2 diabetes, and cardiovascular disease. Further exacerbating this systemic dysfunction is gut microbiota dysbiosis, which promotes metabolic endotoxemia and neuroendocrine dysregulation, impacting hypothalamic function, central hormone resistance, and reproductive health. Epigenetic modifications also serve as crucial mediators, translating environmental exposures into altered gene expression that perpetuates susceptibility across generations. This review summarises the current understanding of obesity by integrating molecular, neuroendocrine, and immunometabolic underpinnings, reinterpreting it as a comprehensive expression of systemic dysfunction. Through this integrated perspective our hope is to highlight the necessity of a paradigm shift towards personalised, multi-targeted interventions that extend beyond conventional weight management. An integrative, translational approach modulating the immunometabolic network, microbiota, and epigenetics is essential to effectively address the global obesity epidemic and its far-reaching health implications. Full article

(This article belongs to the Special Issue Molecular Research in Obesity and Obesity Related Disorders: 3rd Edition)

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30 pages, 1344 KB

Open AccessReview

Impact of Maternal Overweight and Obesity on Adipokines During Pregnancy and Lactation

by Anita Froń, Paulina Tomecka and Magdalena Orczyk-Pawiłowicz

Int. J. Mol. Sci. 2025, 26(19), 9757; https://doi.org/10.3390/ijms26199757 - 7 Oct 2025

Cited by 3 | Viewed by 3418

Abstract

Maternal overweight and obesity have reached global epidemic levels, altering metabolic adaptations during pregnancy and lactation. Beyond their well-known impact on gestational outcomes, elevated BMI profoundly influences the secretion of adipokines—hormones derived from adipose tissue that circulate in maternal blood and are secreted [...] Read more.

Maternal overweight and obesity have reached global epidemic levels, altering metabolic adaptations during pregnancy and lactation. Beyond their well-known impact on gestational outcomes, elevated BMI profoundly influences the secretion of adipokines—hormones derived from adipose tissue that circulate in maternal blood and are secreted into breast milk—thereby directly linking maternal metabolism to offspring development. In this state-of-the-art narrative review, we synthesize current evidence on how maternal overweight and obesity shape concentrations of key adipokines (leptin, adiponectin, ghrelin, obestatin, and resistin) in serum, cord blood and breast milk. Excess maternal weight robustly increases leptin, while effects on adiponectin, ghrelin, obestatin, and resistin remain uncertain. To our knowledge, this is the first review to focus specifically on the impact of maternal overweight and obesity on adipokine alterations across both pregnancy and lactation. Future studies should apply standardized sampling and analytical protocols and use longitudinal designs including body composition assessments to clarify their role in maternal and child metabolic health. Full article

(This article belongs to the Special Issue Molecular Research in Obesity and Obesity Related Disorders: 3rd Edition)

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20 pages, 1779 KB

Open AccessReview

Epicardial Adipose Tissue—A Novel Therapeutic Target in Obesity Cardiomyopathy

by Kacper Wiszniewski, Anna Grudniewska, Ilona Szabłowska-Gadomska, Ewa Pilichowska-Paszkiet, Beata Zaborska, Wojciech Zgliczyński, Piotr Dudek, Wojciech Bik, Marcin Sota and Beata Mrozikiewicz-Rakowska

Int. J. Mol. Sci. 2025, 26(16), 7963; https://doi.org/10.3390/ijms26167963 - 18 Aug 2025

Cited by 7 | Viewed by 3947

Abstract

Obesity is strongly associated with an increased risk of heart failure. Recent studies indicate that epicardial adipose tissue plays a critical role in the development of obesity-related cardiomyopathy. This distinct visceral fat depot, located between the myocardium and the visceral pericardium, is involved [...] Read more.

Obesity is strongly associated with an increased risk of heart failure. Recent studies indicate that epicardial adipose tissue plays a critical role in the development of obesity-related cardiomyopathy. This distinct visceral fat depot, located between the myocardium and the visceral pericardium, is involved in direct cross-talk with the adjacent myocardium, influencing both its structural integrity and electrophysiological function. This review aims to provide an up-to-date overview of the morphological, metabolic, immunological, and functional alterations of this adipose compartment in the context of obesity, and to explore its contribution to the pathogenesis of heart failure. Moreover, the article synthesizes current evidence on the potential cardioprotective effects of emerging anti-obesity pharmacotherapies—particularly GLP-1 and dual GLP-1/GIP receptor agonists—on metabolic pathways associated with epicardial fat that are implicated in obesity-induced cardiomyopathy. Further clinical trials are required to clarify the impact of these therapies on the course and prognosis of heart failure, as well as on the epidemiology and societal burden of the disease. Full article

(This article belongs to the Special Issue Molecular Research in Obesity and Obesity Related Disorders: 3rd Edition)

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21 pages, 333 KB

Open AccessReview

Incorporating Postbiotics into Intervention for Managing Obesity

by Emília Hijová, Izabela Bertková and Jana Štofilová

Int. J. Mol. Sci. 2025, 26(11), 5362; https://doi.org/10.3390/ijms26115362 - 3 Jun 2025

Cited by 1 | Viewed by 4040

Abstract

Obesity is reaching global epidemic proportions worldwide, posing a significant burden on individual health and society. Altered gut microbiota is considered a key factor in the pathogenesis of many diseases, producing metabolites that contribute to the health-beneficial properties of postbiotics. Postbiotics, bioactive microbial [...] Read more.

Obesity is reaching global epidemic proportions worldwide, posing a significant burden on individual health and society. Altered gut microbiota is considered a key factor in the pathogenesis of many diseases, producing metabolites that contribute to the health-beneficial properties of postbiotics. Postbiotics, bioactive microbial components derived from probiotics, are emerging as a valuable strategy in modern medicine and a promising alternative for managing obesity without the need for live bacteria. This work provides a comprehensive overview of the potential health benefits of postbiotics, particularly in relation to obesity, which represents an important health challenge. Despite the encouraging insights into the health benefits of postbiotics, we highlight the need for further research to clarify the mechanisms and the specific roles of different postbiotic components. Integrating postbiotics into health interventions has the potential to enhance preventive care and significantly improve health outcomes in at-risk populations. Full article

(This article belongs to the Special Issue Molecular Research in Obesity and Obesity Related Disorders: 3rd Edition)

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