Search Results (631)

Ambient temperature is a continuous environmental input that affects energy homeostasis through integrated physiological programs. In mammals, thermal cues detected by cutaneous and visceral sensors are conveyed through spinal, vagal, and sympathetic pathways. They are complemented by circulating mediators from the gut, liver, and adipose tissue. These signals converge on brainstem–hypothalamic networks, including the preoptic area and arcuate nucleus, to coordinate feeding behavior, thermogenesis, vasomotor tone, and endocrine outputs. Recent circuit-mapping and single-cell approaches have refined the cellular logic governing the distinct architectures of cold- and heat-defense programs. This review synthesizes these advances to illustrate how a plastic effector network maintains systemic energy homeostasis. Finally, we highlight the translational implications of these thermosensory mechanisms for treating obesity and type 2 diabetes. Full article

Background: Unhealthy expansion of adipose tissue (AT) due to excessive dietary intake of omega-6 or overnutrition stimulates the overaccumulation of the extracellular matrix (ECM), resulting in AT metabolic dysregulation. Hypertrophic conditions, excessive adipose depots, and hypoxia stimulate the overproduction of collagenous and non-collagenous proteins, which pathophysiologically initiate the pro-fibrotic signaling pathway associated with fibrosis progression, resulting in atherosclerosis and cardiovascular diseases. Methods: We aimed to investigate adipocyte plasticity in response to a varying ratio of omega-3 (ω3) to omega-6 (ω6) supplementation during the chemically induced adipogenic differentiation of human mesenchymal stem cells. Additionally, changes in lipid accumulation, adipocyte hypertrophy and hyperplasia, active lipid metabolites, and inflammatory cytokine profiles were evaluated. Furthermore, conditioned media from adipocytes treated with different ω3/ω6 ratios were applied to platelets to assess inflammatory responses through prostaglandin and thromboxane measurements. Results: A 1:3 ratio of ω3/ω6 (20:60 µM) significantly reduced lipid accumulation, promoted brown-like adipocyte morphology, and decreased apoptosis and reactive oxygen species (ROS) generation, as confirmed via FACS analysis. Transcriptional control of adipose tissue expansion was confirmed by the downregulation of LIPIN1 and COL1A1 mRNA expression and p-prostaglandin12-R protein levels in a 1:3 ratio when compared with 1:1, 1:2, 1:4, or 2:6 ratios of ω3/ω6. Notably, a 1:3 ratio of fatty-acid-treated adipocyte-conditioned media-treated platelets significantly reduced platelet activation and aggregation, as evidenced by lower p-thromboxane A2 protein levels. Conclusions: Supplementation with a 1:3 (20:60 µM) ω3/ω6 ratio favored the development of lean adipocytes, evidenced by the decreased lipid storage achieved by mitochondrial thermogenesis, which attenuated minimal adipocyte expansion and metabolic inflammation. Full article

Adipose tissue functions not only as a primary energy reservoir but also as a metabolically active endocrine organ. However, the morphological and molecular differences among adipose depots from different anatomical sites in Yili horses remain unclear. This study aimed to compare the morphological characteristics and proteomic profiles of subcutaneous adipose tissue (SAT) and pericardial adipose tissue (PCAT). To this end, adipose tissue samples from 18 Yili horses were analyzed using hematoxylin and eosin (H&E) staining, while a subset of samples from 6 horses was subjected to proteomic analysis. The results demonstrated that adipocytes in PCAT showed significantly larger areas and diameters but a lower number per field than those in SAT (p < 0.01). Proteomic profiling identified 451 differentially expressed proteins (DEPs) between SAT and PCAT. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses indicated that these DEPs were primarily involved in fatty acid catabolism, glycolysis, ECM–receptor interaction, thermogenesis, Wnt signaling, and other related pathways. Notably, enrichment analyses further revealed that SAT exhibited more active substrate utilization, energy metabolism, and lipid turnover, whereas PCAT was more associated with structural regulation and cardiovascular-related signaling pathways. Furthermore, correlation analysis between adipocyte morphological metrics and proteomic data identified ACAA2, ENO1, TPI1, PLIN1, COL6A3, and ITGB1 as candidate proteins regulating the site-specific differences in morphology and metabolic function between SAT and PCAT. These findings reveal distinct morphological and proteomic features of different adipose depots in Yili horses, providing a foundation for understanding depot-specific adipose function and its underlying regulatory mechanisms. Full article

Background: Circadian disruption exacerbates type 2 diabetes mellitus (T2DM). Time-restricted feeding (TRF) and exercise (EX) improve metabolic health, but their combinatory effect remains unclear. This study investigated whether combined TRF and EX additively ameliorates metabolism via circadian reprogramming in db/db mice. Methods: Eight-week-old male db/db mice were assigned to control (Con), diabetic model (DM), TRF (8 h feeding window), EX (treadmill, 60 min/day, 5 days/week), or combined TRF + EX groups for 8 weeks (n = 8/group). Body weight, glucose/insulin tolerance, and 24 h energy metabolism (CLAMS) were assessed. Mitochondrial function, oxidative stress, inflammation, and expression of mitophagy (Pink1, Park2, Bnip3, Fundc1) and thermogenic (Ucp1, Pgc1a, Prdm16, Cidea) genes were measured. Results: Compared with the con group, DM mice showed obesity, hyperglycemia and blunted circadian metabolic rhythm. The TRF and EX groups improved these defects. Specifically, combined TRF + EX reduced fasting blood glucose from 25.3 ± 3.1 mmol/L (DM) to 13.2 ± 1.8 mmol/L (p < 0.05), body weight from 49.8 ± 2.5 g to 39.5 ± 1.7 g (p < 0.05), and body fat percentage from 45.6 ± 3.2% to 32.1 ± 2.2% (p < 0.05). GTT area under the curve (AUC) decreased from 3711.0 ± 186.5 (DM) to 2118.0 ± 112.4 (p < 0.05), and ITT AUC decreased from 2617.5 ± 135.8 to 1260.0 ± 68.9 (p < 0.05). Notably, the combination of TRF + EX produced greater effects than either intervention alone: body weight, fasting blood glucose, and glucose/insulin tolerance were greatly improved (p < 0.05). In addition, compared with the DM group, the diurnal metabolic amplitude and phase were improved in the TRF or EX group; the combination group showed further improvements in these parameters. Furthermore, TRF and EX each resulted in significantly higher expression of key thermogenic genes (Ucp1, Pgc1a, Prdm16, Cidea) in white adipose tissue (WAT) and brown adipose tissue (BAT) (p < 0.05), and the TRF + EX group showed the highest expression levels. Combined intervention also restored skeletal muscle SOD activity (31.2 ± 2.9 U/mg prot vs. DM 20.1 ± 2.5 U/mg prot, p < 0.05) and reduced serum TNF-α (28.5 ± 4.5 pg/mL vs. DM 65.8 ± 8.5 pg/mL, p < 0.05) and IL-6 (21.6 ± 3.8 pg/mL vs. DM 50.3 ± 7.1 pg/mL, p < 0.05). Conclusions: TRF + EX additively restores metabolic homeostasis in diabetes by re-entraining circadian energy rhythms, improving mitochondrial quality, and activating adipose thermogenesis, supporting further investigation of integrated lifestyle timing as a potential therapeutic strategy. Full article

Nutrient-sensing nuclear receptors (NSNRs), including PPARs, FXR, LXRs, RAR/RXR, VDR, and related orphan receptors, integrate a molecular interface that allows diet to communicate directly with the genome. By binding fatty acids, bile acids, sterols, vitamins, polyphenols, and other food-derived metabolites, NSNRs translate qualitative and quantitative features of the diet into coordinated transcriptional programmes across metabolically active organs. This ligand-dependent signalling network integrates dietary information to orchestrate inter-organ lipid and glucose metabolism, mitochondrial function, thermogenesis, and immune response, thereby enabling the organism to adapt dynamically to fasting–feeding cycles. In this review, we synthesise current evidence on the integrated roles of major NSNRs in the liver, skeletal muscle, white and brown adipose tissue, and kidney, emphasising how receptor networks within and between metabolic organs collectively govern energy expenditure, substrate partitioning, and systemic metabolic flexibility. We propose a conceptual framework in which diet functions as an “external endocrine organ”, acting as the primary source of chemically diverse NSNR ligands, while metabolic tissues serve as secondary signal amplifiers and integrators. Through circulating lipid species, bile acids, oxysterols, and other metabolites, these organs engage in continuous bidirectional communication that reprograms NSNR activity across tissues. We then examine how the global shift from minimally processed, nutrient-rich foods to nutrient-poor, energy-dense ultra-processed diets leads to a reduction in NSNR ligand diversity, promoting hepatic steatosis, muscle metabolic inflexibility, adipose tissue dysfunction, renal lipotoxicity, and chronic low-grade inflammation, ultimately causing obesity, type 2 diabetes, and cardiometabolic disease. Finally, we explore strategies to restore NSNR function, including Mediterranean and plant-based dietary patterns, as well as diets enriched with ω-3 polyunsaturated fatty acids, monounsaturated fats, and polyphenols. By integrating molecular, physiological, and clinical evidence, this review aims to clarify how NSNR networks translate dietary cues into coordinated inter-organ metabolism and how nutrient-poor diets lead to metabolic diseases trough a loss of metabolic information, rather than merely by energy excess. This framework supports a paradigm shift from calorie-centred nutrition to diet quality as the main therapeutic target for preventing metabolic diseases and promoting health. Full article

This study investigates the genetic diversity, population structure, and adaptive differentiation of Yunnan native cattle (YNC) using whole-genome SNP data from 457 individuals, representing eight cattle populations and two closely related bovine species (Zhongdian yak and Dulong gayal). Genetic diversity analyses revealed a distinct latitudinal gradient from north to south, with the highest diversity observed in the northern Diqing (DQC) and Zhaotong (ZTC) populations. The observed population structure was largely consistent with geographic distribution, identifying distinct ancestral components and complex admixture patterns. Genome-wide selective sweep scans revealed several key candidate genes underlying local adaptation. Notably, GRIA4 and DUOXA2 were associated with cold tolerance in northern populations, and ST3GAL3 and MST1 were implicated in heat stress adaptation in southern populations. Genome-wide balancing selection analyses further detected significant loci, such as MGST1 and SLC36A1, where divergent haplotype frequencies reflected differential selective pressures on milk-related traits between northern and southern populations. Additionally, we detected signals of historical introgression from Zhongdian yak into DQC cattle, highlighting the introgressed gene SLIT3 as a potential candidate associated with high-altitude thermogenesis. Collectively, these results provide a comprehensive genomic framework for the management and conservation of indigenous bovine genetic resources in Southwest China. Full article

The initial carbon-to-nitrogen (C/N) ratio is a fundamental parameter for aerobic composting, with a generally recommended optimal range of 25:1 to 30:1. However, in practical applications, the optimal C/N ratio often deviates from the recommended value. We attribute this discrepancy to the limitations of traditional stoichiometric methods in assessing the bioavailability of carbon and nitrogen sources. This study investigated how carbon bioavailability governs composting efficiency and product quality. Laboratory-scale aerobic composting experiments were conducted using six types of raw crop straws and two physically pretreated straws, representing a biodegradability gradient. Results demonstrated that carbon bioavailability significantly modulated the composting performance. Substrates rich in labile carbon pool (LCP), such as wheat straw and extruded cassava plant residue, demonstrated superior thermogenesis, humification, and seed germination indices compared to those dominated by recalcitrant carbon pool (RCP), such as untreated cassava plant residue. Principal component analysis confirmed a strong positive correlation between LCP content and key quality indicators. Microbiological analysis revealed that carbon source variations shaped bacterial succession: Bacteroidota abundance correlated positively with LCP, driving rapid initial degradation, whereas Pseudomonadota were more abundant in RCP-rich treatments, suggesting a role in complex polymer breakdown. This study confirmed that carbon bioavailability, rather than the bulk C/N ratio alone, is a critical limiting factor. This finding logically extends to the role of nitrogen bioavailability, suggesting that a “biochemical C/N ratio”—accounting for the lability of both carbon and nitrogen—could be a more accurate predictor of aerobic composting performance. Full article

Ubiquitin-specific protease 2 (USP2) is a deubiquitinase that controls various cellular events, including cell cycle progression and tumorigenesis. Along with cell culture models, mouse models induced using chemical blockers and gene engineering have substantially contributed to our knowledge of the crucial roles of USP2 in energy metabolism and metabolic disorders. This review summarizes the evidence of the role of USP2 in regulating energy metabolism in mice and cells under physiological and pathological conditions. In hepatocytes, a short isoform of USP2, USP2b, aggravates type 2 diabetes and metabolic dysfunction-associated steatotic liver disease. Meanwhile, a long isoform of USP2 in adipose tissue macrophages, USP2a, attenuates the onset of diabetes. USP2a mitigates insulin resistance and subsequent muscle atrophy. In ventromedial hypothalamic neurons, USP2b inhibits an increase in blood glucose by repressing hepatic glycogenolysis. In addition to regulating diabetes, USP2 isoforms potentially regulate the progression of atherosclerosis by modulating macrophages and hepatocytes. In brown adipose tissue, USP2a regulates thermogenesis, thus influencing systemic energy control. Meanwhile, in testicular macrophages, USP2 protects the mitochondrial respiration of sperm and consequently contributes to maintaining the quality of frozen sperm for use in the treatment of male infertility. As USP2 is distributed to multiple cellular components, it mediates the polyubiquitination of various molecules. For instance, USP2 modulates the stability of various transcription regulators, including C/EBP-α, PPARγ, EBF2, and PGC1α. The accumulating evidence indicates that USP2 functions as a modulatory molecule for energy metabolism across organs. Full article

This review examines the current state of development and application of artificial intelligence (AI) tools for monitoring nutrition and physical activity in individuals with obesity, with a focus on the physiological complexity of energy balance and the role of chrono-nutrition. Energy intake and expenditure are dynamically coupled and circadian-regulated: meal timing and movement patterns influence insulin sensitivity, thermogenesis, and Non-Exercise Activity Thermogenesis within the same day. Traditional monitoring methods suffer from recall bias and low granularity, while isolated sensors operate in data silos, limiting accuracy. Effective solutions require multimodal, continuous, and temporally aligned data streams. Current AI models exhibit critical limitations in obesity-specific contexts: inaccurate gait and energy expenditure estimates due to biomechanical differences, dietary models underestimating glycemic variability, poor performance on mixed dishes, sauces, and culturally diverse foods, and a lack of validation against gold standards such as doubly labelled water (DLW) and weighed food records. This review proposes a paradigm shift toward obesity-specific AI design, including enriched datasets and multimodal integration. Physical activity monitoring faces similar challenges: systematic measurement bias in wearables, sensor placement issues, and algorithms trained on normal-weight cohorts. In the GLP-1/GIP era, if transparency, ethical safeguards, and equitable access are ensured, AI will act as a catalyst for personalized care, remote monitoring, trial optimization, and next-generation drug discovery. In conclusion, the integration of AI with rigorous validation procedures and inclusive sampling strategies is essential to achieve reliable, fair, and clinically relevant monitoring approaches for obesity management. Full article

Direct measurement of thermogenic heat production remains a major challenge in adipose biology. Isothermal microcalorimetry offers a label-free approach to quantify metabolic heat output, yet key parameters governing its application to adipose tissue remain poorly defined. Here, we systematically evaluate the use of the CalScreener isothermal microcalorimetry platform to quantify thermogenic heat production across multiple adipose models, including adipocyte spheroids, freshly isolated adipocytes, and intact adipose tissue explants. Heat production scaled with spheroid size within a defined range and increased linearly with spheroid number per well, demonstrating the quantitative sensitivity of the calorimetric measurements. Pharmacological modulation of mitochondrial respiration in cultured primary beige adipocytes demonstrated that oxidative phosphorylation is a major driver of the calorimetric heat signal, including heat generation associated with mitochondrial proton leak. Freshly isolated adipocytes and intact adipose tissue exhibited depot-specific thermogenic activity and retained responsiveness to β-adrenergic stimulation ex vivo. Across adipose depots, intact tissue explants revealed unexpected differences in thermogenic heat production that were not fully reflected by thermogenic gene expression, highlighting divergence between molecular and functional readouts. Intact adipose tissue maintained measurable thermogenic heat production following extended ex vivo handling in nutrient-containing medium, such that tissues collected across a prolonged harvest window exhibited comparable calorimetric activity, enabling batch analysis of large experimental cohorts. Microcalorimetry further resolved regional differences in thermogenic heat production within the inguinal adipose depot following cold exposure. Together, these findings define key experimental considerations for applying isothermal microcalorimetry to adipose biology and demonstrate its utility for directly quantifying thermogenic metabolism in cells and intact tissues. Full article

Objective: Based on previous findings on the Lingguizhugan (LGZG)-mediated gut–liver axis, this study clarifies the therapeutic mechanisms of LGZG in metabolic dysfunction-associated steatotic liver disease (MASLD), with a focus on the gut microbiota–bile acid–TGR5 (GPBAR1) axis. Methods: C57BL/6J mice were fed a high-fat diet (HFD) for 8 weeks to induce MASLD, followed by 4-week LGZG intervention (21.57 g/kg/day, oral gavage). Metabolic phenotypes, gut microbiota (16S rRNA sequencing), serum/hepatic bile acids (targeted metabolomics), and molecular targets (qPCR/Western blot) were analyzed. Results: LGZG significantly alleviated HFD-induced obesity, insulin resistance, and hepatic steatosis, while enhancing whole-body energy expenditure (increased oxygen consumption (VO₂), and heat production (p < 0.05). It also reduced serum ALT (p < 0.001) and AST levels (p < 0.01). Mechanistically, LGZG remodeled the gut microbiota, specifically increasing Akkermansia, Bifidobacterium and Lachnospiraceae_NK4A236_group while decreasing Lactobacillus. This shift inhibited the intestinal FXR-Fgf15 axis, concurrently activating the hepatic alternative bile acid synthesis pathway (upregulating CYP27A1 and CYP7B1 protein expression; p < 0.001 and p < 0.01, respectively). Consequently, systemic accumulation of non-12α-hydroxylated bile acids (non-12-OH BAs) such as hyocholic acid (HCA) and 7-ketolithocholic acid (7-ketoLCA) occurred—known TGR5 agonists and intestinal FXR antagonists. These changes elevated serum GLP-1 levels (p < 0.05) and activated adipose TGR5-cAMP/PKA/CREB signaling. The metabolic benefits primarily originated from non-12-OH BAs enrichment and TGR5-mediated adipose browning, not hepatic FXR activation. Conclusions: Our findings show that LGZG ameliorates MASLD by remodeling bile acid profiles via intestinal FXR-Fgf15 axis inhibition and hepatic alternative synthesis pathway activation. This study highlights the TGR5-targeting properties of LGZG, providing a mechanistic basis for its therapeutic use in metabolic disorders. Full article

Background: The UCP1 A-3826G polymorphism, located in the gene’s regulatory region, is associated with obesity and altered fat metabolism. Because UCP1 plays a central role in thermogenesis, variation in its expression may influence metabolic efficiency and dietary fat preference. Methods: We examined associations between the A-3826G polymorphism and food preferences in healthy young Japanese adults (50 males, 48 females). Preferences for high-fat and basic-taste foods were assessed using a self-administered questionnaire, with sweet foods classified as low- or high-fat. Genotypes (AA, AG, GG) were analyzed using a two-way mixed-design ANOVA to evaluate genotype × fat level interactions. Results: Preference scores for basic tastes did not differ significantly among genotypes in either sex (except for sour taste in males). In males, no significant genotype × fat level interaction was observed, although AA carriers preferred high-fat to low-fat sweet foods (p < 0.05). In females, a significant genotype × fat level interaction was detected (p < 0.01), with AG carriers showing lower preference for high-fat sweet foods. Conclusions: These findings indicate that the UCP1 A-3826G polymorphism may modulate preference for high-fat sweet foods in a sex-dependent manner, suggesting a link between thermogenic genetic variation and dietary fat preference relevant to obesity prevention. Full article

Obesity is characterized by abnormal adipose tissue expansion and energy metabolism imbalance. Browning of white adipose tissue (WAT), wherein white adipocytes acquire thermogenic properties similar to brown adipose tissue, represents a key mechanism for increasing energy expenditure. Although ginseng (Panax ginseng C.A. Meyer) is widely recognized as a health-promoting botanical, its role in WAT browning has not been fully elucidated. This review summarizes evidence that ginseng and its bioactive components regulate major thermogenic pathways, including β-adrenergic/cyclic adenosine monophosphate-protein kinase (cAMP-PKA) signaling, AMP-activated protein kinase (AMPK), and the peroxisome proliferator-activated receptor γ (PPARγ)/coactivator 1α (PGC-1α) axis, thereby upregulating key markers such as uncoupling protein 1 (UCP1), PR domain containing 16 (PRDM16) and type II iodothyronine deiodinase (DIO2). These effects promote mitochondrial function and fatty acid oxidation, reduce lipogenesis, alleviate inflammation, and improve insulin sensitivity, collectively fostering a microenvironment conducive to browning. Furthermore, fermentation has been found to enhance the bioactivity and thermogenic efficacy of ginseng. Recent evidence indicates that gut microbiota and their metabolites—such as short-chain fatty acids, unsaturated fatty acids, and bile acids—play a notable role in ginseng-induced thermogenesis via receptors including G-protein-coupled receptor 41/43 (GPR41/43), takeda G-protein-coupled receptor 5 (TGR5), and farnesoid X receptor (FXR). These multi-organ interaction networks involving the gut–fat, gut–liver, and gut–brain axes reflect the role of ginseng in integrating systemic metabolism. In summary, this review discusses the multi-level regulatory network through which ginseng promotes WAT browning, providing a mechanistic basis for its potential application in body weight and metabolic health management. Full article

This study investigates the mechanisms underlying drought adaptability in Duolang sheep, a local breed from two distinct habitats in Xinjiang—an arid southern region and a grassland northern region—aiming to identify key factors driving differential environmental adaptation. Integrated multi-omics analyses were performed, including serum biochemical assays, untargeted metabolomics of perirenal and tail fat tissues, and transcriptomic profiling of lung, liver, and kidney samples. Our results revealed notable differences: (1) serum levels of GSH-Px, IL-2, and IgG were significantly higher in the southern group (p < 0.01); (2) metabolomic analysis identified key differential metabolites, including EPA (involved in unsaturated fatty acid biosynthesis), choline (glycerophospholipid metabolism), L-serine and glutathione (cofactor biosynthesis), and taurine (sulfur metabolism); and (3) transcriptomic analysis revealed significant differential expression of genes such as FGF21 (thermogenesis), CD14 and DUSP2 (MAPK signaling pathway), GOT1 (arginine biosynthesis), and AVPR2 (vasopressin-regulated water reabsorption). Integrative correlation analysis further indicated that glutathione, EPA, GOT1, and CD14 are involved in energy and lipid metabolism, while taurine, AVPR2, and DUSP2 contribute to oxidative stress resistance and immune regulation. These molecular and metabolic adjustments collectively enhance drought adaptability in southern Xinjiang Duolang sheep. In conclusion, adaptation to arid environments requires enhanced antioxidant capacity and immune function, with metabolites such as EPA supporting lipid metabolism and genes such as FGF21 regulating fatty acid oxidation to limit triglyceride accumulation. Full article

Adipose tissues (ATs) are dynamic and heterogeneous organs divided into three distinct categories, including white, beige, and brown ATs. Collectively, they contribute to systemic energy homeostasis in various ways. White adipocytes primarily store excess energy, whereas brown and beige adipocytes dissipate energy as heat through non-shivering thermogenesis. Recent advances in multi-omics technologies have transformed our understanding of adipocyte biology, enabling comprehensive interrogation of transcriptional, epigenetic, proteomic, and metabolomic networks that define adipocyte identity and function. Transcriptomic studies reveal distinct gene signatures underlying thermogenic activation and lineage commitment, while epigenomic profiling highlights regulatory elements that orchestrate adipocyte plasticity, particularly the inducible browning of white fat. Proteomic and metabolomic analyses further uncover mitochondrial remodeling, lipid turnover pathways, and metabolite, hormone interactions that regulate thermogenic capacity and metabolic health. Integrating these multi-layered datasets provides systems-level insights into the roles of environmental cues, such as diet and temperature, and endogenous factors, including hormonal signaling, circadian rhythms, and genetic background, in reshaping adipocyte phenotypes and influencing whole-body metabolism. Multi-omics approaches are increasingly identifying potential novel biomarkers and therapeutic targets aiming to enhance the activity of brown and beige adipocyte to combat obesity and metabolic disorders. Overall, these technologies provide a powerful framework for elucidating the complexity of ATs and advancing precision strategies for metabolic disease management and prevention. Full article