Search Results (181)

The purpose of this study was to determine the effects of essential oil inhalation on body weight, blood lipid profile, and liver and adipose tissue in mice. Middle-aged male mice (C57BL/6J) were exposed to Lavandula angustifolia (LO) and Citrus aurantium (CAO) essential oils for 7 weeks and compared to mice that did not receive essential oil inhalation treatment. Liver, white adipose tissue, and brown adipose tissue were sampled, kept at −80 °C. Although essential oil inhalation increased feed intake and body weight compared to control group, the amount of weight gain per feed intake was lower in the C. aurantium essential oil group. Moreover, relative weight of fat to body weight, liver fat amount, and blood cholesterol was lower, and triglyceride levels were significantly reduced. Reverse transcription polymerase chain reaction (RT-PCR) expression profiling of genes related to lipid metabolism confirmed changes in the regulation of thermogenesis-related gene Ucp1 and the cholesterol synthesis-related genes Hmgcs1 and Hmgcr. The inhalation of C. aurantium essential oil did not reduce the feed intake in mice; however, its effectiveness in suppressing the increases in body weight and fat mass was demonstrated. Full article

C-phycocyanin (CPC), a bioactive compound derived from Spirulina, has been described as a molecule with antioxidant and anti-inflammatory properties. It has also been demonstrated that sustainably obtained CPC effectively inhibited body mass gain, regulated serum leptin and resistin levels, and prevented the onset of a pro-inflammatory state in Swiss mice fed a hyperlipidic diet. These results highlighted the anti-obesogenic potential of CPC. Brown adipose tissue (BAT) has been identified as a promising target in the treatment of obesity, playing a role in energy expenditure. In this study, Swiss mice fed a high-fat diet were supplemented with 500 mg/kg body weight of CPC daily for 12 and 16 weeks. BAT was collected, and Western blot and ELISA were performed. A reduction in pro-inflammatory cytokines, as well as a decrease in leptin levels was observed in the tissue, which was also associated with a reduction in BAT relative weight to body mass. Furthermore, CPC administration was able to modulate uncoupling protein 1 (UCP1) levels, which is crucial in the thermogenesis process. Therefore, this study demonstrated that supplementation with CPC reduces inflammatory cytokines associated with detrimental effects in the BAT, emerging as a tool in combating obesity and improving BAT function. Full article

Sarcopenic obesity (SO) is a metabolic disorder for which no effective pharmacological treatments are currently available. Cistanoside F (Cis), a phenoxyethanol-derived compound, remains relatively unexplored in the context of lipid metabolism regulation, as well as its potential mechanisms and therapeutic applications in metabolic disorders. Consequently, this study aimed to evaluate the potential of Cis in ameliorating the pathological manifestations of SO in C2C12 cells. Two classical adipogenic differentiation models using C2C12 cells were employed to quantitatively assess the ability of Cis to inhibit lipid droplet formation, utilizing Oil Red O staining coupled with high-content imaging analysis. Markers associated with adipogenic and myogenic differentiation were examined using quantitative real-time PCR and Western blotting. Our experimental findings demonstrated that Cis significantly attenuated lipid droplet accumulation and promoted muscle protein synthesis via the modulation of PPARγ, ATGL, CPT1b, and UCP1 expression during lipogenic differentiation of C2C12 cells. Cis significantly upregulated the phosphorylation and expression levels of key metabolic regulators, including p-AMPK/AMPK, p-ACC1/ACC1, and MHC. We identified a positive regulatory feedback mechanism between AMPK signaling and MHC expression in the adipogenic differentiation model, suggesting that Cis exerts its therapeutic effects through AMPK-dependent pathways. This is the first study to provide the first experimental evidence supporting the therapeutic potential of Cis for metabolic regulation, targeting adiposity reduction and muscle mass enhancement. Furthermore, Cis exhibited potent anti-inflammatory properties, as demonstrated by its ability to significantly downregulate proinflammatory mediators, including IL-6 and p-NF-κB/NF-κB, during adipogenic differentiation. These novel findings regarding the anti-inflammatory mechanisms of Cis will form the basis for our subsequent in-depth mechanistic investigations. Full article

The gut-liver-adipose axis plays a pivotal role in metabolic regulation, and its dysregulation contributes to obesity and metabolic syndrome. Probiotics and polycosanol have shown potential in modulating gut barrier integrity, lipid metabolism, and inflammation. This study aimed to evaluate their combined effects using an in vitro model of the gut-liver-adipose axis. Transwell^® system was used to recreate the interaction between intestinal (CaCo-2), hepatic (HepG2), and adipose (3T3-L1) cells. Cells were treated with Bifidobacterium bifidum GM-25, Bifidobacterium infantis GM-21, Lacticaseibacillus rhamnosus GM-28, and polycosanols. The effects were assessed by analyzing intestinal barrier integrity (TEER, tight junction proteins), hepatic and adipose lipid accumulation (Oil Red O staining), oxidative stress (ROS production, lipid peroxidation), inflammation (TNF-α) and lipid metabolism (CD36, PPARγ, AMPK and SREBP-1 levels). Probiotics and polycosanols improved intestinal integrity, increased butyrate production, and reduced ROS levels. Hepatic lipid accumulation was significantly decreased, with enhanced PPARγ and AMPK activation. In adipocytes, probiotic-polycosanols treatment suppressed SREBP-1 expression, enhanced lipid oxidation, and promoted UCP1 and PGC-1α expression, suggesting activation of thermogenic pathways. These findings underline a possible biological relevance of probiotics and polycosanols in modulating metabolic pathways, improving gut barrier integrity, and reducing inflammation, supporting their role as functional ingredients for metabolic health. Full article

Oxidative stress poses a significant challenge in livestock production, impairing intestinal function, nutrient absorption, and overall animal performance. Uncoupling protein 2 (UCP2) is a mitochondrial regulator known for its protective effects against oxidative damage, but its specific function in porcine intestinal epithelial cells and its regulation by genipin—a natural UCP2 inhibitor with potential therapeutic properties—remains unclear. In this study, we cloned and overexpressed the porcine UCP2 gene in intestinal porcine epithelial cells (IPEC-J2), generating a stable UCP2-overexpressing cell line (IPEC-J2-UCP2). Under hydrogen peroxide-induced oxidative stress, UCP2 overexpression significantly improved cell viability, reduced reactive oxygen species (ROS) levels, and enhanced antioxidant enzyme activities (SOD, GPx, and CAT). Additionally, UCP2 upregulated the anti-apoptotic gene Bcl-2 and downregulated pro-apoptotic genes (Fas, Caspase-3, and Bax), indicating a protective role against oxidative stress-induced apoptosis. We also investigated the regulatory effects of genipin on UCP2. Under non-stress conditions, genipin mildly promoted anti-apoptotic gene expression. However, under oxidative stress, genipin strongly inhibited UCP2 expression, exacerbated ROS accumulation, reduced cell viability, and increased expression of pro-apoptotic markers, particularly Caspase-3 and Bax. These findings reveal that UCP2 plays a critical role in protecting porcine intestinal epithelial cells from oxidative injury and that genipin exerts context-dependent effects on cell fate by modulating UCP2. This study provides a mechanistic basis for targeting UCP2 to manage oxidative stress and improve intestinal health and performance in pigs. Full article

Obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) are major contributors to the rise in metabolic disorders, particularly in developed countries. Despite the need for effective therapies, natural product-based interventions remain underexplored. This study investigated the therapeutic effects of Endarachne binghamiae, a type of brown algae, hot water extract (EB-WE) in ameliorating obesity and MASLD using high-fat diet (HFD)-induced ICR mice for an acute obesity model (4-week HFD feeding) and C57BL/6 mice for a long-term MASLD model (12-week HFD feeding). EB-WE administration significantly reduced body and organ weights and improved serum lipid markers, such as triglycerides (TG), total cholesterol (T-CHO), HDL (high-density lipoprotein), LDL (low-density lipoprotein), adiponectin, and apolipoprotein A1 (ApoA1). mRNA expression analysis of liver and skeletal muscle tissues revealed that EB-WE upregulated Ampkα and Cpt1 while downregulating Cebpα and Srebp1, suppressing lipogenic signaling. Additionally, EB-WE activated brown adipose tissue through Pgc1α and Ucp1, contributing to fatty liver alleviation. Western blot analysis of liver tissues demonstrated that EB-WE enhanced AMPK phosphorylation and modulated lipid metabolism by upregulating PGC-1α and UCP-1 and downregulating PPAR-γ, C/EBP-α, and FABP4 proteins. It also reduced oxidation markers, such as OxLDL (oxidized low-density lipoprotein) and ApoB (apolipoprotein B), while increasing ApoA1 levels. EB-WE suppressed lipid peroxidation by modulating oxidative stress markers, such as SOD (superoxide dismutase), CAT (catalase), GSH (glutathione), and MDA (malondialdehyde), in liver tissues. Furthermore, EB-WE regulated the glucose regulatory pathway in the liver and muscle by inhibiting the expression of Sirt1, Sirt4, Glut2, and Glut4 while increasing the expression of Nrf2 and Ho1. Tentative liquid chromatography–tandem mass spectrometry (LC-MS/MS) analysis for EB-WE identified bioactive compounds, such as pyropheophorbide A and digiprolactone, which are known to have antioxidant or metabolic regulatory activities. These findings suggest that EB-WE improves obesity and MASLD through regulation of metabolic pathways, glucose homeostasis, and antioxidant activity, making it a promising candidate for natural product-based functional foods and pharmaceuticals targeting metabolic diseases. Full article

Background: Whether intestinal epithelial cells can regulate distant adipose tissue remains a mystery. Methods: Cold-stimulated intestinal epithelial cell-derived exosomes (Cold IEC-Exo) play a pivotal role in enhancing adipose thermogenesis and metabolic homeostasis, as demonstrated in this study. Results: IEC-Exo can accumulate in adipose tissue. Compared with IEC-Exo derived from room temperature mice (RT IEC-Exo), Cold IEC-Exo significantly enhanced the thermogenesis of adipose. In vitro, Cold IEC-Exo directly stimulated thermogenesis in primary adipocytes by elevating oxygen consumption rate, proton leak, and fatty acid uptake, with no effect on glucose uptake. Small RNA sequencing identified miR-674-3p as a key mediator enriched in Cold IEC-Exo. miR-674-3p mimicry replicated Cold IEC-Exo effects, augmenting Ucp1 expression, mitochondrial uncoupling, and fatty acid utilization in adipocytes. Local overexpression of miR-674-3p in BAT and sWAT via AAV in vivo enhanced thermogenesis and attenuated diet-induced glucose intolerance. Conclusions: These findings establish that Cold IEC-Exo, via miR-674-3p transfer, drive adipose thermogenic activation and mitigate metabolic dysfunction, highlighting their therapeutic potential in obesity-related disorders. Full article

Background: Diet-derived advanced glycation end products (dAGEs) are closely associated with obesity and metabolic disorders. This study investigates the therapeutic potential of myriocin (Myr), a sphingolipid synthesis inhibitor, in counteracting dAGE-induced obesity and its underlying mechanisms. Methods: Male C57BL/6J wild-type mice were randomly assigned to receive either a low-AGE diet or a high-AGE diet with or without the administration of myriocin for a duration of 24 weeks. At the end of the experimental period, blood samples, whole livers, and adipose tissues were harvested for subsequent biochemical, histological, and molecular analyses. Results: Using a 24-week high-AGE diet mouse model, we demonstrate that Myr significantly reduces body weight gain (by 76%) and adipose tissue accumulation, while alleviating hepatic steatosis. Myr improves glucose homeostasis by lowering fasting blood glucose (a 44.5% reduction), enhancing oral glucose tolerance, and restoring hepatic glycolysis/gluconeogenesis balance via upregulating glucokinase and suppressing G6pc. Notably, Myr reduces serum LDL-C, TG, and TC levels by 52.3%, 51.8%, and 48.8%, respectively, and ameliorates liver dysfunction as evidenced by normalized ALT/AST activities. Metabolomics reveal Myr reshapes amino acid, carbohydrate, and lipid metabolism pathways. Mechanistically, Myr suppresses lipogenesis by downregulating Srebp1, Fasn, and Acc, while activating AMPK-PGC1α signaling to enhance mitochondrial biogenesis (a 2.1-fold increase in mtDNA) and thermogenesis via Ucp1 upregulation in brown and white adipose tissues. Conclusions: Our findings unveil Myr as a novel dual regulator of lipid and glucose metabolism through AMPK-PGC1α-mediated mitochondrial activation, providing the first evidence of sphingolipid inhibition as a therapeutic strategy against dAGE-induced metabolic syndrome. This study establishes a multifaceted mechanism involving hepatic lipid regulation, adipose browning, and systemic metabolic reprogramming, advancing potential clinical applications for obesity-related disorders. Full article

The Regulator of G Protein Signaling 14 (RGS14) knockout (KO) mouse is a model of healthful longevity, i.e., its lifespan is prolonged and demonstrates enhanced exercise performance and protection against heart disease and hypertension. In this investigation, we found the RGS14 KO mouse is also protected against obesity and glucose intolerance by promoting a low white adipose tissue (WAT) phenotype with increased brown adipose tissue (BAT). This was confirmed by lower body weight, lower white adipocyte size, increased metabolism and improved glucose tolerance and insulin sensitivity. Upon examination of the white adipose tissue, RGS14 KO exhibited increased expression of “beiging” genes as well as significant increase in Uncoupling protein-1 (UCP-1) expression. The mechanism behind this protection was due to its unique brown adipose tissue. This was determined by BAT transplantation, which led to a reversal of phenotype, such that RGS14 BAT recipients developed protection similar to intact RGS14 KO mice, and the RGS14 KO BAT donors lost their protection. Thus, two novel mechanisms mediating obesity and glucose intolerance were found, i.e., inhibition of RGS14 and its BAT. Full article

Uncoupling protein 2 (UCP2) plays an important role in normal cells because it mitigates the cytotoxic effect of reactive oxygen species (ROS). However, its overexpression in cancer cells is related to drug resistance and increased cell proliferation due to a decrease in ROS production. In this context, molecules that regulate or block UCP2 have potential as anticancer agents. (-)-Epicatechin, a flavonoid that inhibits cell proliferation, increases ROS, and induces apoptosis in cancerous cells, was evaluated for its effects on UCP2 gene expression. For this purpose, the real-time quantitative polymerase chain reaction (qRT–PCR) and Western blotting were performed in MDA-MB-231 and MCF-10A cells to determine the effects of (-)-epicatechin on UCP2 expression. Furthermore, the impact of (-)-epicatechin on cell viability was also determined. To analyze the transcriptional regulation of the UCP2 gene by (-)-epicatechin, a 5′-region of the human UCP2 gene (−2093/+297) was amplified, sequenced, cloned, and inserted into a reporter plasmid. To analyze the promoter activity and regulatory motif involved in the effects of (-)-epicatechin, several deletions of the UCP2 promoter were generated and transfected into MDA-MB-231 and MCF-10A cells. An electrophoretic mobility shift assay (EMSA) was carried out to detect the interaction between DNA and proteins involved in the effect of (-)-epicatechin. The increased expression of the UCP2 gene in MDA-MB-231 cells was decreased by (-)-epicatechin, and the opposite effect was observed in MCF-10A cells. The promoter region of the human UCP2 gene (−2093/+297) showed activity, which was decreased by (-)-epicatechin. A sequence of 117 bp located at position −109 b to +8 b has a fragment of 90 bp that is related to the (-)-epicatechin effect. Bioinformatics analysis and EMSA of this sequence revealed the presence of a regulatory site for a protein with zinc fingers. The presence of a response element to (-)-epicatechin in the human UCP2 promoter revealed that the inhibition of this gene in MDA-MB-231 breast cancer cells occurred at the transcriptional level. In this study, we propose the mechanism of action of (-)-epicatechin that could aid in cancer treatment. Full article

Obesity is characterized by an excessive imbalance in energy metabolism and is associated with metabolic syndrome. Mammals have two types of adipose tissue: white adipose tissue (WAT) and brown adipose tissue (BAT). These are key factors in regulating the energy balance. Strategies aimed at reducing obesity should encompass not only the prevention of lipid accumulation but also the stimulation of browning in both WAT and BAT, with the aim of enhancing energy expenditure. In this study, the mechanism by which Lactobacillus brevis-fermented gamma-aminobutyric acid (LB-GABA) prevents obesity was investigated, as well as whether it induces lipolysis and browning in WAT using 3T3-L1 adipocytes. The expression of proteins involved in signaling pathways regulating lipid accumulation and degradation, as well as browning, was measured using Western blotting analysis. We demonstrated that LB-GABA significantly inhibited lipid accumulation by suppressing adipogenesis and lipogenesis. In addition, the microscopic analysis of WAT demonstrated that LB-GABA reduced the adipocyte size and the number of lipid droplets. Moreover, Western blot analysis revealed that GABA increased lipolysis and activated the protein kinase A (PKA) signaling pathway, which promotes uncoupling protein 1 (UCP1)-mediated WAT browning. In conclusion, these results suggest that LB-GABA activates energy expenditure through lipid metabolism regulation and exerts anti-obesity effects. Full article

Sheep (Ovis aries), domesticated from wild Asian mouflon ~10,000 years ago, are an important livestock species adapted to various ecological environments. Recent advancements in high-throughput sequencing and global environmental databases have facilitated the exploration of genetic–environmental associations, uncovering the genetic and epigenetic mechanisms behind sheep’s adaptation to multiple environments. Studies show that HIF-1α and EPAS1 enhance high-altitude adaptation via hypoxic stress regulation; UCP1 contributes to cold adaptation through non-shivering thermogenesis; SLC4A4 and GPX3 increase drought resistance by regulating renal water reabsorption; and SOCS2 likely plays a role in metabolic and stress response regulation. Additionally, sheep adapt to temperature, drought, and environmental stress through DNA methylation, transcriptional regulation (e.g., SOD1, GPX4), heat shock proteins (e.g., HSP70), and metabolic pathways (e.g., UCP1). These findings offer valuable insights for improving sheep breeding and genetic enhancement. This review summarizes the mechanisms of adaptation to high altitude, cold, heat, drought, and comprehensive climate stress. Full article

Cold exposure is a regulatory biological functions in animals. The interaction of thermogenesis and energy metabolism in brown adipose tissue (BAT) is important for metabolic regulation in cold stress. Brown adipocytes (BAs) produce uncoupling protein 1 (UCP1) in mitochondria, activating non-shivering thermogenesis (NST) by uncoupling fuel combustion from ATP production in response to cold stimuli. To elucidate the mechanisms underlying thermogenesis and energy metabolism in BAT under cold stress, we explored how cold exposure triggers the activation of BAT thermogenesis and regulates overall energy metabolism. First, we briefly outline the precursor composition and function of BA. Second, we explore the roles of the cAMP- protein kinase A (PKA) and adenosine monophosphate-activated protein kinase (AMPK) signaling pathways in thermogenesis and energy metabolism in BA during cold stress. Then, we analyze the mechanism by which BA regulates mitochondria homeostasis and energy balance during cold stress. This research reveals potential therapeutic targets, such as PKA, AMPK, UCP1 and PGC-1α, which can be used to develop innovative strategies for treating metabolic diseases. Furthermore, it provides theoretical support for optimizing cold stress response strategies, including the pharmacological activation of BAT and the genetic modulation of thermogenic pathways, to improve energy homeostasis in livestock. Full article

In mammals, exposure to low temperatures induces white adipose tissue (WAT) browning and alters lipid metabolism to promote thermogenesis, thereby maintaining body temperature. However, this response varies across different adipose depots. In this study, Hezuo pigs were exposed to either room temperature (23 ± 2 °C) or low temperature (−15 ± 2 °C) for periods of 12 h, 24 h, 48 h, 5 d, 10 d, and 15 d. Inguinal fat (IF) and perirenal fat (PF) were collected and analyzed using hematoxylin and eosin (HE) staining, transmission electron microscopy, RT-qPCR, and RNA-seq. Following cryoexposure, our results demonstrated a significant increase in adipocyte number and a corresponding decrease in cross-sectional area in both IF and PF groups from 24 h to 10 d. While adipocyte numbers were elevated at 12 h and 15 d, these changes were not statistically significant. Moreover, lipid droplets and mitochondria were more abundant, and the mRNA expression levels of thermogenic genes UCP3 and PGC-1α were significantly higher compared to the control group during the 24 h-10 d cold exposure period. No significant changes were observed in the other groups. RNA-seq data indicated that the lipid metabolism of IF and PF peaked on day 5 of low-temperature treatment. In IF tissue, lipid metabolism is mainly regulated by genes such as FABP4, WNT10B, PCK1, PLIN1, LEPR, and ADIPOQ. These genes are involved in the classical lipid metabolism pathway and provide energy for cold adaptation. In contrast, in PF tissue, genes like ATP5F1A, ATP5PO, SDHB, NDUFS8, SDHA, and COX5A play roles within the neurodegenerative disease pathway, and PF tissue has a positive impact on the process related to degenerative diseases. Further investigation is needed to clarify the functions of these candidate genes in lipid metabolism in Hezuo pigs and to explore the genetic mechanisms underlying the cold-resistance traits in local pig populations. Full article

Brown adipose tissue (BAT) is a critical regulator of non-shivering thermogenesis and energy expenditure, offering significant potential for addressing obesity and associated metabolic disorders. Isoliquiritigenin (ISL), a natural flavonoid, has shown promising therapeutic effects in lipid metabolism-related diseases. This study aimed to explore the effects of ISL on lipid metabolism and obesity using a high-fat-diet (HFD)-induced obesity model in mice. Mice were subjected to an HFD and treated with ISL via gavage. The results demonstrated that ISL treatment significantly reduced HFD-induced weight gain and upregulated the expression of key thermogenic genes, suggesting enhanced BAT activity and thermogenesis. In vitro experiments using C3H10-T1/2 cells further supported these findings, as ISL treatment markedly increased the expression of UCP1 and PPARGC1a, which are critical regulators of thermogenesis. To elucidate the molecular mechanisms underlying ISL’s effects, we conducted a transcriptomic analysis of BAT from ISL-treated mice. Pathway enrichment analysis revealed that differentially expressed genes were predominantly associated with metabolic processes, including the tricarboxylic acid (TCA) cycle, oxidative phosphorylation, and fatty acid degradation. These pathways are integral to energy metabolism and thermogenesis, providing mechanistic insights into ISL’s anti-obesity effects. Additionally, ISL treatment significantly downregulated the expression of NNAT and SGK1, genes implicated in lipid metabolism and energy homeostasis. These findings suggest that ISL modulates BAT function by regulating the expression of these genes, thereby influencing lipid deposition and thermogenic capacity. In summary, this study suggests that ISL treatment has the potential to mitigate HFD-induced obesity by promoting BAT thermogenesis and modulating lipid metabolism. The molecular mechanisms involve the regulation of key metabolic pathways and genes, such as NNAT and SGK1, highlighting ISL’s potential as a therapeutic agent for obesity and related metabolic disorders. Full article