Search Results (1,328)

Dysregulated lipid metabolism constitutes the fundamental etiology underlying the global burden of obesity and its associated metabolic disorders. N⁶-methyladenosine (m⁶A) is the most abundant reversible chemical modification on messenger RNA and influences virtually every aspect of RNA metabolism. Recent studies demonstrate that m⁶A mediates regulatory networks governing lipid metabolism and contributes to the pathogenesis of multiple metabolic diseases. However, the precise roles of m⁶A in lipid metabolism and related metabolic disorders remain incompletely understood. This review positions m⁶A modification as a central epigenetic switch that governs lipid homeostasis. We first summarize the molecular components of the dynamic m⁶A regulatory machinery and delineate the mechanisms by which it controls key lipid metabolic processes, with an emphasis on adipogenesis, thermogenesis and lipolysis. Building on this, we further discuss how dysregulated m⁶A acts as a shared upstream driver linking obesity, type 2 diabetes (T2D), metabolic dysfunction-associated steatotic liver disease (MASLD), and insulin resistance through tissue-specific and inter-organ communication mechanisms. We also evaluate the potential of targeting m⁶A regulators as therapeutic strategies for precision intervention in metabolic diseases. Ultimately, deciphering the complex interplay between m⁶A modification and lipid homeostasis offers a promising frontier for the development of epitranscriptome-targeted precision medicine against obesity and its associated metabolic disorders. Full article

Medium- and long-chain fatty acids (MLFAs) are increasingly recognized not only as metabolic substrates but also as precursors of diverse bioactive metabolites generated through host and microbial transformations. Recent advances in analytical chemistry and microbiome research have revealed that gut microorganisms catalyze extensive modifications of dietary MLFAs—producing hydroxylated, conjugated, and keto-fatty acids with enhanced potency toward host receptors. These metabolites exhibit dual activity on classical metabolic receptors, including FFAR1/4 and PPARα/γ, as well as ectopically expressed chemosensory receptors such as olfactory receptors (ORs) and bitter taste receptors (TAS2Rs). This expanded receptor landscape establishes a previously unrecognized chemosensory–metabolic axis that integrates dietary signals, microbial metabolism, and host physiology. Microbial MLFA derivatives such as 10-hydroxyoctadecenoic acid and conjugated linoleic acid regulate incretin secretion, adipogenesis, macrophage polarization, and intestinal barrier function through coordinated activation of FFARs and PPARs. Concurrently, dicarboxylic acids such as azelaic acid activate Olfr544 to modulate lipolysis, ketogenesis, GLP-1 release, and feeding behavior. TAS2Rs also sense oxidized lipids, linking lipid metabolism to immune regulation and enteroendocrine signaling. Collectively, these pathways highlight the microbiome as a metabolic transducer that converts dietary lipids into signaling molecules influencing endocrine, immune, and gut–brain circuits. Understanding the mechanisms governing MLFA bioconversion and receptor engagement provides new opportunities for therapeutic and nutritional intervention. Targeting ORs and TAS2Rs, engineering probiotics to enhance beneficial FA-derived metabolites, and developing receptor-selective synthetic analogs represent promising strategies. Future progress will require integrative approaches combining physiology, biochemistry, metabolomics, and microbial genomics to elucidate receptor specificity and host variability. Full article

Cellular senescence is a stress-induced process that contributes to adipose tissue dysfunction by promoting inflammation, impaired adipogenesis, and insulin resistance, alterations that are closely associated with age-related cellular dysfunction and metabolic disorders. In this study, we evaluated the protective role of chlorogenic acid (CGA), a polyphenol with known antioxidant and anti-inflammatory properties, against oxidative stress-induced senescence in murine 3T3-L1 adipocytes. The results obtained showed that CGA treatment significantly alleviated the senescent phenotype by restoring Lamin B1 levels and the Bcl-2/Bax ratio. Additionally, CGA downregulated key senescence-related cell cycle progression markers, modulating p53, p21, and MAPK signaling. CGA also restored insulin signaling through the PI3K-AKT-GLUT4 axis and improved glucose uptake, while attenuating oxidative stress, inflammatory cytokine expression, and extracellular matrix remodeling factors associated with SASP. Collectively, these findings support the role of CGA as a promising senotherapeutic nutraceutical able to reduce adipocyte senescence and its metabolic consequences, offering novel insights for the development of dietary supplements targeting age-related cellular dysfunction. Full article

Obesity plays a crucial role in the progression of insulin resistance and type 2 diabetes which are related to inflammation and liver disease. GATA-3 is a transcription factor that is involved in adipogenesis and inflammation. Therefore, it could be a potential therapeutic target for obesity-associated metabolic disorders. This study aimed to examine the effects of GATA-3 suppression on body weight, fat depot redistribution, liver histopathology, and inflammatory markers in transgenic db/db obese mice. Male db/db mice received subcutaneous injections of GATA-3-specific DNAzyme (hgd40; 10 or 100 µg/mL), pioglitazone (as a positive control), or vehicle only (as a negative control), twice weekly for two weeks. Body weight, organ weights, liver histopathology, mRNA expression of selected genes and serum cytokine levels were assessed. GATA-3 expression was not region specific, and its suppression did not significantly affect fat depot distribution or organ weights. However, the low dose of hgd40 accelerated body weight gain transiently. It also increased Il10 mRNA expression in the liver and significantly increased IL-10 protein concentration in the serum. In addition, a high dose of hgd40 resulted in a marked decrease in hepatocyte ballooning degeneration. These findings suggest that GATA-3 suppression may modulate inflammation and liver injury in obesity, warranting further investigation into its therapeutic potential for obesity-related metabolic disorders. Full article

Brown adipose tissue (BAT) has emerged as a promising therapeutic target for metabolic disorders such as type 2 diabetes and obesity. To advance research on BAT activation and elucidate the mechanisms underlying adipogenesis, it is crucial to develop a reliable in vitro model. This study aimed to optimize the differentiation of adipose-derived stem cells (ADSCs) into beige adipocytes and to validate the protocol using primary human ADSCs obtained from eight donors. Protocol optimization was first performed with commercial ADSCs, testing more than 30 combinations of adipogenic conditions. Differentiation was assessed by microscopy, Oil Red O staining, and uncoupling protein 1 (UCP1) expression via reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot. Among the key adipogenic factors, rosiglitazone proved more effective than indomethacin. Extending the induction phase from 4 to 8 days and maintaining dexamethasone throughout the culture markedly enhanced differentiation efficiency. Serum concentration above 5% was inhibitory, while optimal conditions were identified as 5 μM rosiglitazone and 20 μg/mL insulin. The optimized protocol successfully induced beige adipogenesis in ADSCs from eight independent donors, though efficiency varied considerably which could be attributed to individual donor variability. These findings provide a robust in vitro model for studying beige fat biology and highlight the relevance of personalized approaches in metabolic research. Full article

Nobiletin, a citrus-derived polymethoxylated flavone, has been reported to exert anti-obesity effects, but its molecular mechanisms remain poorly understood. This study aimed to investigate whether nobiletin suppresses adipogenesis and promotes browning in 3T3-L1 adipocytes by modulating exosomal microRNAs (miRNAs) and AMPK signaling. To this end, we treated 3T3-L1 adipocytes with various concentrations of nobiletin and evaluated gene and protein expression by RT-qPCR and Western blotting. Nobiletin significantly reduced intracellular lipid accumulation at 50 μM (p < 0.001) and downregulated key adipogenic transcription factors, PPARγ, C/EBPα, and SREBP-1c, and suppressed the lipogenic enzyme FAS, while activating the AMPK/ACC signaling pathway. Concomitantly, it enhanced the expression of thermogenic markers UCP-1, PRDM16, and PGC-1α, indicating a metabolic shift toward energy expenditure. Exosomal RNA-seq revealed 10 differentially expressed miRNAs, of which miR-181d-5p (3.1-fold) and miR-221-3p (2.4-fold) were upregulated, whereas miR-205-5p (−2.9-fold), miR-331-3p (−3.2-fold), miR-130b-3p (−2.6-fold), miR-143-5p (−2.9-fold), miR-183-3p (−2.8-fold), miR-196b-5p (−2.4-fold), miR-26b-3p (−2.2-fold), and miR-378d (−2.7-fold) were verified by RT-qPCR after nobiletin treatment (50 μM). These miRNAs are functionally associated with adipogenic and thermogenic pathways, supporting a regulatory role of the exosomal miRNA network in nobiletin’s action. Collectively, our results identify a novel exosome–miRNA–AMPK axis underlying the anti-adipogenic and browning-inducing activities of nobiletin, highlighting its potential as a therapeutic phytochemical for obesity prevention. Full article

Peroxisome proliferator-activated receptor γ (PPARγ) plays a crucial role in the differentiation and maturation of preadipocytes. PPARγ promotes adipogenesis by inducing the expression of fatty acid-binding protein 4 (FABP4). Uncoupling protein 1 (UCP1) is involved in non-shivering thermogenesis and adipocyte browning. The present study aimed to examine the effects of luteolin and apigenin on the gene expression levels and protein concentrations of PPARγ and FABP4, which are involved in adipogenesis, and their effect on UCP1, a thermogenic protein, in the 3T3-L1 preadipocyte cell line. Luteolin and apigenin were prepared at concentrations of 10, 20, and 40 µM and applied to 3T3-L1 preadipocytes during differentiation and maturation. Gene expression levels were measured by real-time PCR, and protein concentrations were measured by ELISA. It was found that the doses used did not cause cytotoxicity in the cells. Luteolin treatment during differentiation and maturation resulted in a decrease in PPARγ and FABP4 gene expression, although the protein concentrations remained unchanged. Additionally, while luteolin treatment did not significantly alter UCP1 gene expression or protein levels during differentiation, it led to a decrease in UCP1 protein concentration during maturation. Apigenin treatment also tended to decrease PPARγ and FABP4 gene expression compared to the control, although no statistical difference was observed. These results suggest that luteolin and apigenin may have regulatory effects on adipogenesis by modulating PPARγ, FABP4, and UCP1 gene expression. Full article

The substantial interest in plant-based drugs or plant-derived phytocompounds drives researchers to conduct comprehensive investigations on their therapeutic properties. Mollugin, one of the major active constituents of Rubia cardifolia, has been well-studied for its pharmacological properties, demonstrating potent anti-inflammatory properties by suppressing the TAK-1-mediated activation of NF-κB/MAPK and enhancing the Nrf2/HO-1-mediated antioxidant response. It exhibits strong anticancer effects through ferroptosis via IGF2BP3/GPX4 pathways, induces mitochondrial apoptosis, and targets NF-κB, ERK, and PI3K/Akt/mTOR to suppress tumor progression. Mollugin also inhibits JAK2/STAT and PARP1 pathways, suppressing IL-1β expression via the modulation of ZFP91. Moreover, it regulates the MAPK/p38 pathway, promotes neuroprotection, and improves cognitive performance through GLP-1 receptor activation. Mollugin promotes osteogenesis by activating the BMP-2/Smad1/5/8 signaling pathway and downregulates MAPK, Akt, and GSK3β expression, leading to the inhibition of osteoclastogenesis. It overcomes multidrug resistance by downregulating MDR1/P-gp, CREB, NF-κB, and COX-2 through AMPK activation. Its antibacterial effect is mediated by strong binding to FUR, UDP, and IpxB proteins in Enterobacter xiangfangensis. Mollugin mitigates Klebsiella pneumoniae infection, suppresses adipogenesis without causing cytotoxicity, and protects endothelial cells via the BDNF/TrkB-Akt signaling pathway. Synthetic derivatives of mollugin, such as oxomollugin and azamollugin, have shown enhanced anticancer and anti-inflammatory effects by regulating EGFR, PKM2, TLR4/MyD88/IRAK/TRAF6, and NF-κB/IRF3 pathways with improved solubility and stability. Collectively, these findings emphasize the broad-spectrum activity of mollugin. This review provides a critical interpretation of the mechanistic pathways regulated by mollugin and its derivatives, emphasizing their pharmacological significance and exploring their potential for future translation as multitarget drug candidates. Full article

Bone Morphogenetic Protein-2 (BMP2) is a growth factor that maintains bone homeostasis through the BMP receptor type Ia (BMPRIa) and type II (BMPRII). BMP2 promotes osteogenesis by inducing the differentiation of bone marrow mesenchymal stem cells (BMSCs) into osteoblasts; however, it can also trigger BMSC differentiation into adipocytes. BMP2’s osteo-inductive ability has made it a potential treatment for osteoporosis, yet its dual role in BMSC differentiation complicates its efficacy. High BMP2 levels cause BMPRIa cleavage, but the downstream effects and the mechanisms governing BMP2-induced osteogenesis or adipogenesis are unresolved. Here, we identify Caspase-1 as a key mediator of BMPRIa cleavage and its downstream effects on adipogenesis. We used primary BMSCs from C57BL/6 mice, stimulated with varying BMP2 concentrations, to explore BMP2-induced BMPRIa cleavage and its impact on PPARγ—a key regulator of adipogenesis. Western blotting and immunostaining using antibodies against BMPRIa and PPARγ uncovered BMPRIa cleavage and revealed the nuclear translocation of the cleaved segment, colocalizing with PPARγ. Caspase-1 inhibition significantly reduced BMPRIa cleavage and PPARγ expression, highlighting its pivotal role in adipogenic differentiation. Understanding the molecular mechanisms of BMP2-induced adipogenesis and Caspase-1 inhibition could improve BMP2 therapeutic efficacy for osteoporosis by promoting osteogenesis over adipogenesis. Full article

Intramuscular fat (IMF) content is a critical determinant of beef quality and is regulated by various factors. However, the molecular mechanisms underlying IMF deposition in cattle remain poorly understood, particularly with regard to multi-omics integrated analyses. In this study, an integrative analysis of transcriptomic and proteomic profiles was performed on intramuscular fat tissue of Jiaxian Red cattle with different marbling grades to identify key genes and pathways involved in intramuscular fat deposition in beef cattle. Integrated analysis showed that 4532 genes were co-expressed at both mRNA and protein level, among which 21 genes exhibited significant differential expression at mRNA and protein level. These genes showed significant enrichment in lipid biosynthesis and metabolic processes. ECHDC1 was selected for in-depth functional studies on bovine intramuscular preadipocyte adipogenesis as a candidate gene via RNA interference and overexpression techniques. The results indicated that knockdown of ECHDC1 inhibited the adipogenesis of bovine intramuscular preadipocytes and significantly upregulated the expression of HSL. Conversely, overexpression of ECHDC1 promoted the adipogenesis of bovine intramuscular preadipocytes, decreased the expression of HSL and increased the expression of FABP4. In summary, these results suggested that ECHDC1 promoted intramuscular fat deposition by attenuating lipolysis rate by downregulating the expression of the lipolytic gene HSL, providing a potential molecular target for enhancing IMF content in beef cattle. Full article

This study investigated the role of SCD5 in bovine preadipocyte proliferation and adipogenic differentiation. SCD5 overexpression suppressed proliferation, reducing the percentage of EdU-positive cells and overall cell viability (p < 0.05). It also downregulated proliferative factors CDK1 and CDK2 (p < 0.05), and reduced lipid accumulation (p < 0.001) along with key adipogenic markers PPARγ, C/EBPα, and FABP4 (p < 0.01). Conversely, SCD5 knockdown promoted these processes. Mechanistically, SCD5 overexpression downregulated WNT5B (p < 0.05), while knockdown had the opposite effect. Silencing WNT5B significantly decreased β-catenin transcription (p < 0.05), total protein (p < 0.05), and phosphorylation (p < 0.001). In conclusion, our findings identify SCD5 as a novel negative regulator of bovine preadipocyte proliferation and differentiation, which exerts its function through the WNT5B/β-catenin signaling axis. This discovery elucidates previously uncharacterized regulatory mechanisms underlying adipogenesis in livestock species. Full article

Obesity is linked to metabolic dysfunction-associated steatotic liver disease (MASLD), but the molecular mechanisms and effective treatments remain unclear. This study investigated whether ST32db, an inducer of activating transcription factor 3 (ATF3), affects lipid metabolism in MASLD. An in vitro model was established involving the treatment of HepG2 cells with 1 mM oleic acid (OA) with or without 20 µM ST32db. In an in vivo model, C57BL/6 mice were fed a high-fat diet (HFD) for 18 weeks to induce obesity and treated or not with ST32db (1 mg kg⁻¹). ST32db significantly decreased intracellular lipid accumulation in OA-treated HepG2 cells. In these cells, ST32db remarkably decreased mRNA and protein levels of adipogenesis- and lipogenesis-related genes and increased mRNA levels of adipose triglyceride lipase (ATGL), a lipolytic enzyme. In HFD-fed mice, the ST32db treatment significantly decreased the liver weight, serum triglycerides, and fat vacuole and triglyceride accumulation in the liver. Livers from these mice also showed significantly decreased CCAAT/enhancer-binding protein β mRNA and protein levels, increased ATF3 mRNA and protein and ATGL mRNA levels, and increased levels of phosphorylated AMP-activated protein kinase (AMPK) and protein kinase A (PKA). These findings suggest that ST32db may exert protective effects against MASLD through activating hepatic AMPK and PKA pathways. Full article

This study investigated meat quality, nutritional characteristics, and transcriptomic regulation in Yunan (YN) black pigs and Huainan (HN) black pigs (n = 6 each). Analysis of fatty acid composition revealed that HN black pigs possessed significantly higher levels of most fatty acids compared to YN black pigs. Notably, the contents of monounsaturated fatty acid C18:1n9c and polyunsaturated fatty acid C18:2n6c in HN black pigs were 1.94-fold and 2.65-fold higher, respectively, than those in YN black pigs. The α-linolenic acid content was also significantly elevated in HN black pigs, indicating an overall higher fatty acid content. Regarding amino acid differences, HN black pigs exhibited significantly higher levels of aspartic acid, glutamic acid, histidine, as well as superior composition of total amino acids, total umami amino acids, and essential amino acids, which contribute to enhanced flavor characteristics and nutritional balance. Transcriptome analysis identified 526 differentially expressed genes in HN vs. YN. KEGG enrichment analysis showed that these genes were involved in many adipogenesis and lipid metabolism signaling pathways, such as biosynthesis of unsaturated fatty acids, fatty acid elongation, apelin signaling pathway and lysine degradation. By integrating transcriptome and protein–protein interaction (PPI) network analyses, we identified key meat quality-related genes: ELOVL6, PRKAG3, ROCK2, and MYH11. miRNA profiling identified ssc-miR-133b, ssc-miR-206, and miR-205 as key regulators of meat quality. This study provides a valuable theoretical foundation for understanding the molecular mechanisms underlying pork quality and offers insights for its future improvement. Full article

Extracellular vesicles (EVs) derived from probiotic bacteria have recently emerged as postbiotic mediators that regulate host cellular responses. This study investigated the effects of EVs from Lactobacillus rhamnosus BS-Pro-08, isolated from kefir grains (Lacto EV), on adipocyte differentiation and lipid metabolism. Lacto EV treatment markedly suppressed the differentiation of 3T3-L1 preadipocytes into mature adipocytes, as reflected by reduced lipid accumulation and decreased expression of the adipogenic transcription factors peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα). This inhibitory effect was most pronounced at the early stage of adipogenesis. In mature adipocytes, Lacto EV enhanced lipolysis in a dose-dependent manner, accompanied by increased glycerol release and total lipase activity. Interestingly, these lipolytic responses occurred despite reduced protein levels of adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL), suggesting that Lacto EVs may mediate an EV-enhanced lipolysis that is not fully explained by canonical ATGL/HSL signaling. Collectively, these findings demonstrate that Lacto EV modulates both adipogenic and lipolytic processes in vitro, providing insight into the metabolic actions of probiotic-derived vesicles. Full article

Background: Obesity is increasingly recognized as a metabolic disorder driven by gut microbiota dysbiosis and chronic low-grade inflammation within adipose tissue. Emerging evidence highlights the gut–adipose tissue axis as a critical mediator of energy balance and metabolic regulation. Marine algae—rich in polysaccharides, polyphenols, and carotenoids—offer bioactive compounds that modulate gut microbial composition and generate beneficial metabolites termed “postbiotics.” Objective: This review aims to comprehensively summarize current advances in understanding how marine-algal-derived postbiotics influence the gut microbiota–adipose tissue axis and contribute to obesity prevention and management. Methods: A structured literature search was conducted across PubMed, Scopus, Web of Science, ScienceDirect, and SpringerLink for studies published between 2015 and October 2025. Eligible studies included in vitro, in vivo, and human trials examining the effects of marine-algal compounds on gut microbiota composition, short-chain fatty acid (SCFA) production, adipose inflammation, and metabolic outcomes. Results: Marine-algal polysaccharides (fucoidan, alginate, laminarin, carrageenan, and ulvan) act as fermentable fibers that enhance SCFA production and enrich beneficial taxa such as Akkermansia, Lactobacillus, and Bacteroides, while reducing endotoxin-producing bacteria. Polyphenols and carotenoids (fucoxanthin, phlorotannins, astaxanthin) directly target adipogenesis, oxidative stress, and adipose browning. Animal studies consistently demonstrate reduced body weight, improved insulin sensitivity, and decreased inflammation following algae supplementation. Human trials—though limited—confirm safety and show microbiota modulation with modest weight loss. Conclusions: Marine-algal-derived postbiotics represent a promising, natural, and sustainable strategy to target the gut microbiota–adipose tissue axis in obesity. They offer multi-targeted mechanisms through microbial and host pathways, supporting their integration into functional food and nutraceutical development. Further clinical research and regulatory standardization are warranted to translate these findings into evidence-based interventions. Full article