Search Results (752)

Atherosclerosis is now recognized as a chronic inflammatory disease of the arterial wall, in which perivascular adipose tissue (PVAT) has evolved from a passive structural component to a key player in regulating vascular homeostasis and the pathophysiology of atherosclerosis, playing an active, not just structural, role. PVAT surrounds blood vessels and influences them metabolically, immunologically, and vascularly by secreting adipokines, cytokines, and other bioactive mediators. Under physiological conditions, PVAT has protective roles, as it produces adiponectin, nitric oxide (NO), and other vasodilatory factors that help maintain vascular tone and reduce inflammation. In particular, brown-like PVAT (rich in Uncoupling Protein-1 (UCP1) and mitochondria) offers significant vasoprotective effects. Under pathological conditions (obesity, dyslipidemia, insulin resistance), PVAT undergoes a phenotypic transition towards a pro-inflammatory profile by increasing leptin, tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) secretion and decreasing adiponectin, contributing to endothelial dysfunction, vascular smooth muscle cell (VSMC) proliferation, local immune cell recruitment, extracellular matrix (ECM) remodeling, and fibrosis. PVAT plays a complex role in vascular health and disease, interacting with systemic metabolism through the secretion of bioactive molecules. Metabolic imbalances can promote PVAT inflammation. Epigenetic alterations and micro ribonucleic acid (miRNAs) can influence PVAT inflammation, and modern imaging methods for PVAT assessment, such as the fat attenuation index (FAI) and artificial intelligence-assisted radiomic profiling, may become predictive biomarkers of cardiac risk. Future directions aim to identify biomarkers and develop targeted therapies that modulate PVAT inflammation and dysfunction in the context of cardiovascular diseases. Full article

Background/Objectives: Obesity is a chronic metabolic disorder characterized by the excessive expansion of adipose tissue and impaired energy homeostasis. Natural products, such as plant extracts, are gaining attention as potential anti-obesity agents. This study aimed to evaluate and compare the anti-obesity effects of ginger (Zingiber officinale Roscoe) extract alone and as a mixture with long pepper (Piper longum L.) extract in a mouse model of high-fat diet-induced obesity. Methods: Male ICR mice were fed a high-fat diet to induce obesity and were orally administered ginger extract (60 mg/kg/day) or a 1:1 mixture of ginger and long pepper extracts (30 mg/kg/day each) for 8 weeks. Body weight, fat mass, glucose tolerance, and serum lipid levels were measured. Results: Ginger extract alone significantly reduced body weight gain and visceral and subcutaneous fat accumulation and improved glucose homeostasis and serum lipid profiles compared to the high-fat diet group. These effects were more pronounced than those observed with the mixture group. Ginger extract upregulated lipolytic markers via activation of the protein kinase A (PKA) signaling pathway and increased expression of uncoupling protein 1 (UCP1), indicating browning of white adipose tissue. Conclusions: Ginger extract alone exhibited significant anti-obesity effects compared to the mixture with long pepper extract. These findings suggest that ginger extract may serve as a promising natural agent for the prevention and management of obesity-related metabolic dysfunction. Full article

Background: Enhancing adipose tissue functionality is a promising cellular-level approach to combating obesity. White adipose tissue (WAT) can acquire beige or brown adipose tissue (BAT)-like properties, characterized by increased thermogenesis and energy dissipation. While the SIRT1-SRSF10–Lipin-1 axis has been identified in hepatocytes, where Lipin-1 regulates triglyceride metabolism, its role in adipocytes remains unclear. This study aimed to investigate the function of Lipin-1 in 3T3-L1 preadipocytes and its interaction with SIRT1, SRSF10, and PPARγ in promoting browning-like transcriptional responses. Methods: Mouse 3T3-L1 preadipocytes were treated during differentiation with either rosiglitazone (RGZ), the SIRT1 activator SRT1720, or the SIRT1 inhibitor EX527. Gene expression was assessed by real-time PCR, and protein levels were measured using the Simple Western blot system. Data were compared with untreated controls and analyzed using GraphPad Prism. Results: Lipin-1 expression was significantly upregulated by RGZ treatment, alongside increased transcription of Sirt1 and Srsf10, supporting the presence of this regulatory axis in adipocytes. Elevated Srsf10 favored the production of the Lipin-1b isoform, whereas SIRT1 inhibition reversed these effects, confirming its upstream role. Pathway activation further enhanced the expression of browning markers, including Ucp1, Pgc1a, PRDM16, and CIDEA. Conclusions: These findings demonstrate that Lipin-1 interacts with the SIRT1–PPARγ–SRSF10 axis in adipocytes and contributes to the acquisition of beige/brown-like characteristics in WAT. This regulatory pathway may represent a potential target for improving lipid metabolism and metabolic health. Full article

Obesity represents a significant global public health challenge, which not only elevates the risk of mortality but also increases the likelihood of chronic diseases. The ongoing obesity epidemic has led to a growing recognition of the detrimental effects of excessive adipose tissue accumulation on male reproductive health. Substantial evidence indicates that obesity adversely affects sperm quality, thereby impairing male fertility. Specifically, obesity is associated with compromised spermatogenesis, erectile dysfunction, and detrimental effects on offspring fertility parameters. These effects are mediated through various mechanisms, including alterations in the hypothalamic–pituitary–gonadal axis, inflammation within the reproductive system, localized caloric excess in reproductive tissues, epigenetic modifications, disruptions in gut microbiota, and heightened oxidative stress levels. While the molecular alterations associated with obesity have been extensively documented, the precise mechanisms by which obesity influences male reproductive function remain inadequately understood. This article aimed to review the classification and distribution of adipose tissue in obesity, the impact of obesity on male fertility, and the potential mechanisms through which obesity affects male reproductive health, thereby offering insights into the prevention and treatment of obesity-related male fertility issues. Full article

Obesity (lipotoxicity) results from a chronic imbalance between energy intake and expenditure. It is strongly associated with type 2 diabetes mellitus (T2DM, glucotoxicity) and considered a major risk factor for the development of metabolic complications. Their convergence constitutes “diabesity”, representing a major challenge for public health worldwide. Limited treatment efficacy highlights the need for novel, multi-targeted therapies. Non-shivering thermogenesis (NST), mediated by brown and beige adipose tissue and skeletal muscle, has emerged as a promising therapy due to its capacity to increase energy expenditure and improve metabolic health. Also, skeletal muscle plays a central role in glucose uptake and lipid oxidation, further highlighting its relevance in diabesity. This review explores current and emerging knowledge on physiological stimuli, including cold exposure, physical activity, and fasting, as well as bioactive ingredients and drugs that stimulate NST in thermogenic tissues. Special emphasis is placed on melatonin as a potential regulator of mitochondrial function and energy balance. The literature search was conducted using MEDLINE and Web of Science. Studies were selected based on scientific relevance, novelty, and mechanistic insight; prioritizing human and high-quality rodent research published in peer-reviewed journals. Evidence shows that multiple interventions enhance NST, leading to improved glucose metabolism, reduced fat accumulation, and increased energy expenditure in humans and/or rodents. Melatonin, in particular, shows promise in modulating thermogenesis through organelle-molecular pathways and mitochondrial protective effects. In conclusion, a multi-target approach through the activation of NST by physiological, nutritional, and pharmacological agents offers an effective and safe treatment for diabesity. Further research is needed to confirm these effects in clinical practice and support their use as effective therapeutic strategies. Full article

Polyphenols have been widely recognized for their potential anti-obesity effects. This study aimed to evaluate the impact of a polyphenol compound-epigallocatechin-3-gallate, quercetin, and rutin (EQR) on obesity-related parameters and gut microbiota composition. After four weeks of high-fat diet (HFD) induction, the obese Wistar male rats received EQR treatment for an additional four weeks. EQR supplementation significantly reduced body weight gain, feed efficiency, adipose tissue accumulation, and liver lipid content in obese rats. Additionally, it enhanced fecal short-chain fatty acid (SCFA) levels and modulated gut microbiota composition. Specifically, EQR treatment significantly induced Fusobacteria, Fusobacteriaceae, Christensenellaceae, Christensenellaceae R-7 group, Lachnoclostridium, Enterorhabdus, and Parvibacter levels and reduced Deferribacteres and Mucispirillum levels. Gene expression analysis in liver, white adipose tissue (WAT), and brown adipose tissue (BAT) revealed that EQR upregulated the expression of liver PPAR-α, WAT SIRT-1, and BAT PGC-1α, while downregulating liver PPAR-γ, liver FATP-1, and WAT FAS, indicating its role in promoting fatty acid oxidation and thermogenesis, as well as suppressing lipid synthesis and transport. In conclusion, EQR demonstrated significant anti-obesity effects by modulating gut microbiota and lipid metabolism, suggesting its potential as a functional ingredient for obesity management. Full article

Regular physical activity induces a dynamic crosstalk between skeletal muscle and adipose tissue, modulating the key molecular pathways that underlie metabolic flexibility, mitochondrial function, and inflammation. This review highlights the role of myokines and adipokines—particularly IL-6, irisin, leptin, and adiponectin—in orchestrating muscle–adipose tissue communication during exercise. Exercise stimulates AMPK, PGC-1α, and SIRT1 signaling, promoting mitochondrial biogenesis, fatty acid oxidation, and autophagy, while also regulating muscle hypertrophy through the PI3K/Akt/mTOR and Wnt/β-catenin pathways. Simultaneously, adipose-derived factors like leptin and adiponectin modulate skeletal muscle metabolism via JAK/STAT3 and AdipoR1-mediated AMPK activation. Additionally, emerging exercise mimetics such as the mitochondrial-derived peptide MOTS-c and myostatin inhibitors are highlighted for their roles in increasing muscle mass, the browning of white adipose tissue, and improving systemic metabolic function. The review also addresses the role of anti-inflammatory compounds, including omega-3 polyunsaturated fatty acids and low-dose aspirin, in mitigating NF-κB and IL-6 signaling to protect mitochondrial health. The resulting metabolic flexibility, defined as the ability to efficiently switch between lipid and glucose oxidation, is enhanced through repeated exercise, counteracting age- and disease-related mitochondrial and functional decline. Together, these adaptations demonstrate the importance of inter-tissue signaling in maintaining energy homeostasis and preventing sarcopenia, obesity, and insulin resistance. Finally, here we propose a stratified treatment algorithm based on common age-related comorbidities, offering a framework for precision-based interventions that may offer a promising strategy to preserve metabolic plasticity and delay the age-associated decline in cardiometabolic health. Full article

Objectives: Obesity has become a major health issue, with multifactorial etiologies involving lifestyle, genetic, and neuroendocrine mechanisms. Despite public health campaigns and lifestyle interventions, long-term weight loss is often difficult to achieve or sustain. This literature review aims to summarize current knowledge on the main molecular mechanisms that hinder weight loss and to summarize the newest therapeutic strategies targeting obesity. Methods: The literature review was conducted using PubMed, Scopus, and Web of Science databases, with a preference for peer-reviewed original articles, systematic reviews, and meta-analyses. Eligible studies were required to be published in the English language and within the last ten years (2015–2025), with the exception of historically significant publications. A total of 112 articles were included in our review. Results: Obesity is a complex, chronic, recurrent metabolic condition that requires personalized, multidisciplinary treatment approaches. In this review, we summarize the major molecular mechanisms underlying weight gain and weight maintenance in obesity. In this literature review, we address the metabolic memory and epigenetics that act through DNA and histone modifications and micro interfering RNAs, resulting in an energy imbalance that can be passed on to further generations. The dysfunction of adipose tissue contributes to chronic low-grade inflammation and insulin resistance, leading to more severe obesity. The ratio of white, beige, and brown adipocytes also plays an important role in regulating energy balance. Novel medical interventions offer promising results in attenuating these mechanisms against successful weight loss. Conclusions: Current interventions, including calorie restriction, physical activity, and pharmacological treatment together, may show great promise in combating obesity, but long-term efficacy and safety remain to be established. Full article

Background/Objectives: Sarcopenic obesity, defined by the coexistence of excessive fat accumulation and progressive muscle loss, is associated with an increased risk of metabolic dysfunction and physical disability. While 5,7-dimethoxyflavone (DMF), a bioactive flavone derived from Kaempferia parviflora, has demonstrated anti-obesity and muscle-preserving properties, its effects on sarcopenic obesity remain unclear. Methods: Four-week-old male C57BL/6J mice were fed a high-fat diet (HFD) for 6 weeks to induce sarcopenic obesity, followed by 8 weeks of continued HFD with the oral administration of DMF. Muscle function was assessed through grip strength and treadmill running tests, while muscle and fat volumes were measured using micro-CT. Mechanistic analyses were performed using gene expression and Western blot analysis. Results: DMF significantly reduced body weight, fat mass, and adipocyte size while enhancing grip strength, endurance, skeletal muscle mass, and the muscle fiber cross-sectional area. In the gastrocnemius muscle, DMF increased the gene expression of peroxisome proliferator-activated receptor gamma coactivator-1α (Ppargc1a) and its isoform Ppargc1a4, thereby promoting mitochondrial biogenesis. It also improved protein turnover by modulating protein synthesis and degradation via the phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin signaling pathway. In subcutaneous and brown adipose tissues, DMF increased mitochondrial DNA content and the expression of thermogenic and beige adipocyte-related genes. These findings suggest that DMF alleviates sarcopenic obesity by improving mitochondrial function and regulating energy metabolism in both skeletal muscle and adipose tissues via PGC-1α-mediated pathways. Thus, DMF represents a promising therapeutic candidate for the integrated management of sarcopenic obesity. Full article

Adipose tissue enlargement in obesity leads to hypoxia, which may promote premature aging. This study aimed to understand the hypoxic response in 3D cultures of SGBS cells, a model for brown-like adipose tissue expressing uncoupling protein 1 (UCP1). Single-nucleus RNA sequencing of SGBS organoids revealed a heterogeneous composition and sub-population-specific responses to hypoxia. The analysis identified a cluster of transcriptional repression, indicating dying cells, and implied a role of ferroptosis in this model. Further experiments with SGBS cells and white adipose tissue-derived stem/progenitor cells showed that Acyl-CoA synthetase long-chain family member 4 (ACSL4), a key enzyme in ferroptosis, is expressed only in the presence of browning factors. Hypoxia downregulated ACSL4 protein in SGBS organoids but induced an inflammaging phenotype. Analysis of brown-like epicardial adipose tissue from cardiac surgery patients revealed a significant positive correlation of ACSL4 mRNA with UCP1 and hypoxia-inducible pro-inflammatory markers, while ACSL4 protein appeared to be inversely correlated. In conclusion, this study demonstrates that adipocytes’ capability to undergo ACSL4-mediated ferroptosis is linked to brown-like adipogenesis, suggesting an opportunity to modulate ferroptotic signaling in adipose tissue. The dual role of hypoxia by inhibiting ACSL4 but promoting inflammaging indicates a relationship between ferroptosis and aging that warrants further investigation. Full article

In recent years, irisin has garnered significant interest among researchers. It is a myokine released by skeletal muscles during physical exercise. Its expression occurs not only in skeletal muscles but also in other organs such as the liver, kidneys, and lungs, where it fulfills important metabolic and protective functions. Irisin is involved in the regulation of energy homeostasis, promotes the browning of adipose tissue, plays a protective role, and influences the body’s adaptation to physical exercise. In the context of internal organ function, studies suggest its potential role in protecting the kidneys from damage, modulating inflammatory processes in the lungs, and supporting liver regeneration. This literature review focuses on analyzing the therapeutic effects of irisin in these organs in relation to the role of physical exercise. Full article

Background: Sodium–glucose cotransporter-2 inhibitors (SGLT2is), initially developed as antihyperglycemic agents, have emerged as multifunctional therapeutics with profound cardiorenal and metabolic benefits. Their unique insulin-independent mechanism, targeting renal glucose reabsorption, distinguishes them from conventional antidiabetic drugs. Mechanisms and Clinical Evidence: SGLT2is induce glycosuria, reduce hyperglycemia, and promote weight loss through increased caloric excretion. Beyond glycemic control, they modulate tubuloglomerular feedback, attenuate glomerular hyperfiltration, and exert systemic effects via natriuresis, ketone utilization, and anti-inflammatory pathways. Landmark trials (DAPA-HF, EMPEROR-Reduced, CREDENCE, DAPA-CKD) demonstrate robust reductions in heart failure (HF) hospitalizations, cardiovascular mortality, and chronic kidney disease (CKD) progression, irrespective of diabetes status. Adipose Tissue and Metabolic Effects: SGLT2is mitigate obesity-associated adiposopathy by shifting macrophage polarization (M1 to M2), reducing proinflammatory cytokines (TNF-α, IL-6), and enhancing adipose tissue browning (UCP1 upregulation) and mitochondrial biogenesis (via PGC-1α/PPARα). Modest weight loss (~2–4 kg) occurs, though compensatory hyperphagia may limit long-term effects. Emerging Applications: Potential roles in non-alcoholic fatty liver disease (NAFLD), polycystic ovary syndrome (PCOS), and neurodegenerative disorders are under investigation, driven by pleiotropic effects on metabolism and inflammation. Conclusions: SGLT2is represent a paradigm shift in managing T2DM, HF, and CKD, with expanding implications for metabolic syndrome. Future research should address interindividual variability, combination therapies, and non-glycemic indications to optimize their therapeutic potential. Full article

Obesity is a chronic disorder associated with serious comorbidities such as diabetes, cardiovascular disease, and cancer. Conventional pharmacological treatments often suffer from limited efficacy, poor selectivity, and undesirable side effects, highlighting the need for more effective alternatives. Nanomedicine offers a promising approach by overcoming these limitations through targeted drug delivery and enhanced therapeutic precision. This review examines key nanotechnological strategies in obesity management, including targeting white adipose tissue (WAT) and the vascular marker prohibitin, promoting WAT browning, and utilizing photothermal therapy and magnetic hyperthermia as nanotheranostic tools. We discuss major nanomedicine platforms—such as liposomes, nanoemulsions, and polymeric nanoparticles—alongside emerging applications in gene nanotherapy and herbal formulations. Potential toxicity concerns are also addressed. In summary, nanomedicine holds substantial potential to revolutionize obesity treatment through targeted, effective, and multifunctional therapeutic strategies. Full article

The kallikrein–kinin system and its B1 and B2 receptors are key regulators in metabolic disorders such as obesity, diabetes, and insulin resistance. Obesity, a chronic and multifactorial condition often associated with comorbidities like type 2 diabetes and dyslipidemia, remains poorly understood at the metabolic level. The kinin B2 receptor (B2R) is involved in blood pressure regulation and glucose metabolism, promoting glucose uptake in skeletal muscle via bradykinin. Studies in B2R-KO mice demonstrate that the absence of this receptor predisposes animals to glucose intolerance under a high-fat diet and impairs adaptive thermogenesis, indicating a protective role for B2R in metabolic homeostasis and insulin sensitivity. In contrast, the kinin B1 receptor (B1R) is inducible under pathological conditions and is activated by kinin metabolites. Mouse models lacking B1R exhibit improved metabolic profiles, including protection against high-fat diet-induced obesity and insulin resistance, enhanced energy expenditure, and increased leptin sensitivity. B1R inactivation in adipocytes enhances insulin responsiveness and glucose tolerance, supporting its role in the development of insulin resistance. Moreover, B1R deficiency improves energy metabolism and thermogenic responses to adrenergic and cold stimuli, promoting the activation of brown adipose tissue and the browning of white adipose tissue. Collectively, these findings suggest that B1R and B2R represent promising therapeutic targets for the treatment of metabolic disorders. Full article

Background: While epicardial adipose tissue (EAT) is a known predictor of adverse cardiovascular outcomes, lipomatous hypertrophy of the interatrial septum (LHIS) is composed of metabolically active fat such as brown adipose tissue, which may exert a different effect. This study investigates the coronary atherosclerosis profile in patients with LHIS using CTA, compared with a propensity score-matched control group. Methods: A total of 142 patients were included (n = 71 with LHIS and n = 71 controls) and propensity score-matched for age, gender, BMI, and the major CV risk factors (matching level, <0.05). CTA imaging parameters included HRP, coronary stenosis severity (CADRADS), and CAC score. Results: The mean age was 60.9 years +/− 10.6, there were nine (6.3%) women, and the mean BMI is 28.04 kg/m² +/− 4.99. HRP prevalence was significantly lower in LHIS patients vs. controls (21.1% vs. 40.8%; p < 0.011), while CAC (p = 0.827) and CADRADS (p = 0.329) were not different, and there was no difference in the obstructive disease rate. There was no difference in lipid panels (cholesterol, LDL, HDL, TG) and statin intake rate. Conclusions: HRP prevalence is lower in patients with LHIS than controls, while coronary stenosis severity and CAC score are not different. Clinical relevance: LHIS may serve as imaging biomarker for reversed CV risk. Full article