TL;DR
Investigating the anti-obesity properties of rabbit meat extract and determining its bioactive peptides found peptide-3(GEAGPQGARG) exhibited the most potent bioactivity, characterized by the upregulation of thermogenic genes and the concurrent downregulation of adipogenic markers within adipocytes.
Metabolic dysfunction–associated steatotic liver disease (MASLD) is closely linked to obesity, insulin resistance, and endocrine dysregulation. Although calorie restriction is widely used for metabolic control, it is often accompanied by unintended skeletal muscle loss, which may negatively affect long-term metabolic outcomes. Therefore, identifying a dietary strategy that improves metabolic health while preserving muscle mass is of clinical importance. This study combined retrospective clinical observations with an in vivo high-fat diet (HFD)-induced obese mouse model to evaluate the effects of low-calorie balanced diet (LCD). Clinical data were used to assess changes in metabolic parameters and body composition. In parallel, obese mice subjected to LCD intervention were evaluated for body weight, glucose metabolism, hepatic steatosis, and skeletal muscle morphology. Gene expression related to hepatic lipid metabolism and muscle atrophy was analyzed. LCD intervention improved metabolic parameters, reduced body weight gain, and alleviated hepatic lipid accumulation in both clinical observations and the animal model. In HFD-fed mice, LCD improved glucose homeostasis and partially reversed hepatic steatosis. Importantly, skeletal muscle structure was preserved, and the expression of muscle atrophy–related genes, including MSTN, FOXO3a, and MuRF1, was reduced. In the liver, LCD decreased the expression of lipogenic genes such as SREBP-1c, FASN, and ACC, while partially restoring fatty acid oxidation–related genes including PPARα and CPT1α. LCD improves metabolic dysfunction and hepatic steatosis while preserving skeletal muscle integrity in obesity. These findings provide translational evidence supporting LCD as a practical dietary strategy for MASLD management and highlight the importance of coordinated metabolic regulation between liver and skeletal muscle.
Obesity develops through progressive metabolic alterations that arise long before overt disease, highlighting the need for pharmacological strategies capable of targeting the earliest tissue adaptations to fat nutrient excess. Skeletal muscle plays a central role in systemic metabolic homeostasis and is among the first organs affected by high-fat diet (HFD) exposure. Oleoylethanolamide (OEA), a peroxisome proliferator-activated receptor alpha (PPAR-α) agonist, exerts broad metabolic actions in obesity, yet its impact on early skeletal muscle remodeling remains unknown. We investigated whether OEA could intercept the initial metabolic adaptations induced by HFD exposure in young rats. Male rats were exposed to HFD for seven weeks and treated with OEA (10mg/kg, i.p.) during the final two weeks. Short-term HFD induced a coordinated remodeling of skeletal muscle characterized by lipid accumulation, suppression of the PPAR-α/CPT-1 axis, altered mitochondrial and redox homeostasis, extracellular matrix remodeling, impaired myogenic signaling, and a shift toward a glycolytic contractile program despite only modest body-weight gain. OEA largely attenuated such alterations, preserving skeletal muscle metabolic and structural homeostasis through coordinated improvement of lipid oxidative metabolism, mitochondrial energetic status, and tissue remodeling. These findings identify skeletal muscle as an early target of fat-induced metabolic dysfunction and support further investigation of OEA as a promising pharmacological strategy to intercept obesity-associated metabolic deterioration before overt obesity develops.
Browning is a process wherein white adipocytes differentiate into brown-like adipocytes. This process is one of the key signatures of overcoming obesity. Notably, several functional foods and dietary supplements can induce browning in human body. One such naturally occurring compound is dehydrozingerone (DHZ), which is known for its beneficial effects, including antioxidant properties. In this study, DHZ was evaluated for its effect on fat reduction in 3T3-L1 cells prior its consideration as a potential anti-obesity therapeutic. The results underpin that DHZ acts as a key activator of browning, as shown by increased expression of brown adipose tissue (BAT) markers such as uncoupling protein 1 (UCP1), PR/SET domain 16 (PRDM16), cell death-inducing DFFA-like effector A (CIDEA), T-box transcription factor 1 (TBX1), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) . These changes in gene expression may be associated with activation of the AMP-activated protein kinase (AMPK) pathway, and potentially mediated by the browning effect of DHZ on 3T3-L1 adipocytes. Furthermore, the treatment of DHZ also increased expression of Carnitine palmitoyltransferase 1 (CPT1), acyl-CoA synthetase long-chain family member (ACSL), and Sirtuin 1 (SIRT1), suggesting enhanced fatty acid oxidation. While the expression of Srebp1 and LpI was reduced. These findings suggest that DHZ may possibly enhances thermogenesis and promote browning in white adipocytes, thereby suppressing lipogenesis. In conclusion, DHZ showed dual effects lipid metabolism, contributing to development of a brown-like phenotype. The results depict that DHZ could serve as a promising therapeutic candidate for the management of obesity. In addition, molecular docking analysis demonstrated strong binding affinity between DHZ and the target protein, further supporting its potential as a novel therapeutic agent. However, these considerations are preliminary, and further studies, including diet-induced animal model, are required to elucidate its mechanism of action.
Obesity and related metabolic complications are associated with adipose tissue (AT) dysfunction, which contributes to metabolic inflexibility. However, the underlying mechanisms remain unclear. Our previous studies demonstrated that a high-fat diet (HFD) induces weight gain, increased fat weight, as well as significant metabolite alterations in serum, liver, and cecum in mice. Therefore, this study aims to investigate the effect of HFD on AT metabolites to elucidate their role in obesity progression. To establish a diet-induced obesity model, nine female Kunming mice were fed a high-fat diet (HFD) for 16 weeks and compared with nine control mice maintained on a normal diet. Subcutaneous abdominal adipose tissue samples (SAAT) were analyzed using ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) coupled with orthogonal partial least squares discriminant analysis (OPLS-DA). By metabolic profiling, 48 significantly different metabolites were identified, including phosphatidylcholines (PCs), lysophosphatidylcholines (LysoPCs), O -phosphoethanolamine, linoleic acid, alpha-linolenic acid, proline betaine, and 3-dehydroxycarnitine. These obesity-associated metabolites were mainly involved in glycerophospholipid metabolism, sphingolipid metabolism, and biosynthesis of unsaturated fatty acids. Among these pathways, glycerophospholipid metabolism exhibited the most pronounced disruption. These identified metabolites in SAAT may aid in understanding of the mechanism by which HFD promotes the progression of obesity and related diseases.
Metabolic dysfunction–associated steatotic liver disease (MASLD) is an increasingly prevalent complication of obesity and metabolic dysregulation, with limited therapies targeting upstream drivers of disease. Adipose tissue has emerged as a central regulator of systemic metabolic homeostasis, where dysfunction contributes to excess free fatty acid flux, chronic inflammation, and hepatic steatosis. In this context, adipose tissue browning—the induction of thermogenically active beige adipocytes within white adipose depots—has gained attention as a potential therapeutic mechanism. Recent advances highlight that adipose browning modulates multiple pathways relevant to MASLD. These include enhanced mitochondrial β-oxidation and energy expenditure, leading to reduced lipid delivery to the liver, as well as endocrine signaling mediated by batokines such as fibroblast growth factor 21 (FGF21), irisin, and neuregulin 4 (Nrg4). Collectively, these pathways influence hepatic lipid metabolism, insulin sensitivity, and inflammatory and fibrotic processes. The preclinical studies consistently demonstrate metabolic and hepatoprotective benefits of browning; however, translational evidence in humans remains limited and heterogeneous. Factors such as reduced thermogenic capacity in obesity, inter-individual variability, and challenges in sustaining browning activation constrain clinical applicability. Overall, adipose tissue browning represents a promising component of a systems-based approach to MASLD. Future work should focus on integrating mechanistic insights with clinical investigation to clarify its therapeutic potential and to identify strategies that enable durable and patient-specific metabolic benefits.
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