Search Results (364)

Background: Cucurbitacin E (CuE), a natural tetracyclic triterpenoid compound extracted from the melon stems of Cucurbitaceae plants, has been reported to exhibit anti-inflammatory and anti-cancer properties, along with the ability to enhance cellular immunity. However, its role and molecular mechanism in regulating lipid metabolism and adipogenesis remain unclear. This study aims to investigate the potential anti-adipogenic and anti-obesity effects of CuE in 3T3-L1 adipocytes. Materials and Methods: 3T3-L1 preadipocytes were cultured and induced to differentiate using a standard adipogenic cocktail containing dexamethasone, 3-isobutyl-1-methylxanthine (IBMX), and insulin (DMI). CuE was administered during the differentiation process at various concentrations. Lipid accumulation was assessed using Oil Red O staining, and cell viability was evaluated via the MTT assay. To determine whether CuE induced apoptosis or necrosis, flow cytometry was performed using annexin V/PI staining. Additional molecular analyses, such as Western blotting and RT-PCR, were used to examine the expression of key adipogenic markers. Results: Treatment with CuE significantly reduced lipid droplet formation in DMI-induced 3T3-L1 adipocytes in a dose-dependent manner, as shown by decreased Oil Red O staining. Importantly, CuE did not induce apoptosis or necrosis in 3T3-L1 cells at effective concentrations, indicating its safety toward normal adipocytes. Moreover, CuE treatment downregulated the expression of adipogenic markers such as PPARγ and C/EBPα at both mRNA and protein levels. Discussion: Our findings suggest that CuE exerts a non-cytotoxic inhibitory effect on adipocyte differentiation and lipid accumulation. This anti-adipogenic effect is likely mediated through the suppression of key transcription factors involved in adipogenesis. The absence of cytotoxicity supports the potential application of CuE as a safe bioactive compound for obesity management. Further investigation is warranted to elucidate the upstream signaling pathways and in vivo efficacy of CuE. Conclusions: Cucurbitacin E effectively inhibits adipogenesis in 3T3-L1 adipocytes without inducing cytotoxic effects, making it a promising candidate for the development of functional foods or therapeutic agents aimed at preventing or treating obesity. This study provides new insights into the molecular basis of CuE’s anti-obesity action and highlights its potential as a natural lipogenesis inhibitor. Full article

Thai fermented soybeans (TFSs) contain phytochemicals with anti-diabetic benefits. In this study, an initial non-optimized TFS extract (TFSE) was prepared using a conventional triplicate 80% ethanol extraction method and evaluated for its biological activity. TFSE effectively reversed TNF-α-induced insulin resistance in 3T3-L1 adipocytes by enhancing insulin-stimulated glucose uptake, indicating anti-diabetic potential. TFSE also upregulated the phosphorylation of AKT (a key insulin signaling mediator) and the expression of adipogenic proteins (PPARγ, CEBPα) in TNF-α-exposed 3T3-L1, suggesting the mitigation of adipocyte dysfunction; however, the results did not reach statistical significance. The conventional extraction process was labor-intensive and time-consuming, and to enhance extraction efficiency and bioactivity, the process was subsequently optimized using environmentally friendly microwave-assisted extraction (MAE) in combination with the Box–Behnken design (BBD) and response surface methodology (RSM). The optimized extract (O-TFSE) was obtained over a significantly shorter extraction time and exhibited higher levels of total flavonoids and antioxidant activity in comparison to TFSE, while showing reduced levels of isoflavones (daidzein, genistein, and glycitein) in relation to TFSE. Interestingly, O-TFSE retained similar efficacy in reversing TNF-α-induced insulin resistance and demonstrated significantly stronger α-glucosidase and α-amylase inhibitory activities, indicating its enhanced potential for diabetes management. These results support the use of MAE as an efficient method for extracting functional compounds from TFS for functional foods targeting insulin resistance and type 2 diabetes mellitus. Full article

Earthworms are valued as a dietary protein source in many regions. Earthworm protein can yield bioactive peptides, but enzymatic hydrolysis is inefficient by commercial proteases, and bioactivity development is still inadequate. This study developed a novel efficient method for degrading earthworm protein and investigated the lipid-lowering activity and mechanism of earthworm peptides. It was found that combining autolysis and alcalase exhibited a higher hydrolysis degree of earthworm protein of 43.64 ± 0.78% compared to using autolysis or alcalase only. The hydrolysate significantly reduced lipid accumulation in steatotic hepatocytes. LC-MS/MS results showed that the primary lipid-lowering peptides (EWPs) in the hydrolysate were small molecule peptides with molecular weights of 500–1000 Da and chain lengths of 4–7 amino acid residues. Western blot results demonstrated that EWP regulated the expression of lipid metabolism-related proteins, including APOC3, HMGCR, PCSK9, SREBP1, C/EBP-α, NPC1L1, PPAR-γ, and CYP7A1. Transcriptomic analysis and validation experiments indicated that the lipid-lowering activity of EWP was associated with its suppression of inflammatory factors, such as IL-6. This study presents an efficient enzymatic hydrolysis strategy for earthworm protein utilization, laying the foundation for its application in functional foods such as protein supplements, nutraceutical capsules, hypoallergenic infant formulas, and sports nutrition products. Full article

Obesity and its associated complications, including oxidative stress, pose significant global health challenges. Natural products offer a promising avenue for developing novel therapeutic strategies. In this study, we investigated the potential of Panax japonicus (T. Nees) C.A. Meyer, a traditional medicinal plant known for its antioxidant and anti-obesity properties. A methanol extract of Panax japonicus and its fractions were evaluated for their in vitro antioxidant activities (tested using DPPH and reducing power assays), pancreatic lipase (PL) inhibitory capacities, and underlying mechanisms of action. The results indicated that the ethyl acetate fraction of P. japonicus (PJEA) exhibited the greatest potency, demonstrating strong antioxidant activity and significantly inhibiting digestive enzyme activity (pancreatic lipase). Mechanistic studies revealed that the PL inhibition was of a mixed type, combining both competitive and non-competitive mechanisms. Furthermore, PJEA demonstrated the ability to inhibit the differentiation of preadipocytes, primarily exerting its anti-adipogenic effects by downregulating the mRNA expression of PPARγ and the gene expression of C/EBPα. In addition, the extract suppressed the gene expression of FAS and ACC in adipose tissue. Isolation of the bioactive compounds from PJEA identified kaempferol 3-O-α-L-rhamnoside and catechin, which potentially contribute to the observed anti-obesity effects. Overall, this study highlights P. japonicus as a promising natural ingredient for scavenging free radicals and managing obesity, suggesting its potential for development into functional foods or therapeutic agents. Full article

Poly-L-lactic acid (PLLA) filler, which increases volume and collagen synthesis, is used for skin rejuvenation. Subcutaneous adipose tissue (SAT) contains precursors that differentiate into mature adipocytes that secrete adiponectin, which modulates SAT function and increases adipogenesis. During aging, adiponectin and precursor cell functions decrease, reducing adipogenesis and facial volume. Adiponectin also increases collagen synthesis by stimulating fibroblasts. After hydrogen peroxide treatment to induce senescent adipocytes (3T3-L1) and aged skin, follow-up PLLA treatment increased adipogenesis by stimulating the nuclear factor erythroid-2-related factor 2 (NRF2)/peroxisome proliferator-activated receptor gamma (PPARγ)/CCAAT/enhancer binding protein alpha (C/EBPα) pathway. This resulted in increased adiponectin secretion, which promoted collagen synthesis and mitigated the loss of SAT volume. In the senescent adipocyte, PLLA increased NRF2/PPARγ/C/EBPα, adipogenesis factors (fatty acid binding protein 4, lipoprotein lipase, and cluster of differentiation 36), lipogenesis factors (ATP citrate lyase, acetyl-CoA carboxylase, and fatty acid synthase), adiponectin, and lipid droplet size. Treatment of senescent fibroblasts with conditioned medium from PLLA-treated adipocytes increased collagen1 and 3 and decreased matrix metalloproteinase1 and 3 expressions. Similarly, PLLA increased NRF2/PPARγ/C/EBPα, adipogenesis, and lipogenesis factors in aged mouse SAT. Also, PLLA increased adiponectin and adipocyte numbers without hypertrophy and increased collagen accumulation and dermal thickness. In summary, PLLA increased adipogenesis and adiponectin, which increased the volume of SAT and collagen synthesis, thereby rejuvenating aged skin. Full article

Obesity is a major metabolic disorder driven by excessive adipogenesis and lipid accumulation. This study investigated the anti-obesity effects and molecular mechanisms of Antrodia cinnamomea alcohol extract (ACE) in 3T3-L1 preadipocytes and a high-fat diet (HFD)-induced obesity mouse model. In vitro, Antrodia cinnamomea alcohol extract significantly inhibited adipocyte differentiation and lipid accumulation in 3T3-L1 cells by downregulating PPARγ and C/EBPα, while activating the AMPK pathway and suppressing MAPK signaling. In vivo, Antrodia cinnamomea alcohol extract administration reduced body weight, adipose tissue mass, and liver lipid accumulation in high-fat diet-fed mice, ameliorating non-alcoholic fatty liver disease (NAFLD) symptoms. Transcriptomic analysis of adipose tissue revealed that Antrodia cinnamomea alcohol extract modulated key gene expression profiles related to fatty acid metabolism and adipogenesis, suppressing lipid synthesis while enhancing β-oxidation. Furthermore, Antrodia cinnamomea alcohol extract rebalanced gut microbiota, increasing beneficial bacterial populations such as Akkermansia and Bifidobacterium, while reducing pro-inflammatory Escherichia-Shigella species. These findings demonstrate that Antrodia cinnamomea alcohol extract exerts multifaceted anti-obesity effects by regulating lipid metabolism, adipogenesis pathways, and gut microbiota composition, highlighting its potential as a natural therapeutic agent for obesity management. Full article

This study aims to evaluate the anti-obesity effects of Ashwagandha (Withania somnifera, AS), Chrysanthemum zawadskii Herbich var. latilobum (Maxim.) Kitamura (C), and their combination (AS:C = 3:1, ASC) in high-fat-diet (HFD)-induced obese animal models. Key metabolic parameters, including body weight, lipid metabolism, adipogenesis, energy expenditure, and glucose homeostasis, were assessed. HFD-fed mice were supplemented with AS25, C25, or ASC at different concentrations (ASC25, ASC50, and ASC100). Body weight, food efficiency ratio (FER), organ and adipose tissue weights were measured. Serum biochemical markers, including lipid profiles, glucose, insulin, and liver enzymes, were analyzed. Western blot analysis was conducted to assess the expression of key proteins involved in adipogenesis, lipogenesis, lipolysis, and energy metabolism. ASC complex supplementation, particularly at higher doses (ASC100), significantly reduced body weight gain, liver weight, and total white adipose tissue (WAT) accumulation. ASC complex groups exhibited improved lipid profiles, with reductions in triglycerides, total cholesterol, and low-density lipoprotein (LDL). Serum glucose, insulin, and HbA1c levels were significantly reduced, suggesting improved insulin sensitivity. Western blot analysis revealed that ASC complex supplementation downregulated key adipogenic markers, including PPARγ, C/EBPα, and SREBP1c, while enhancing adiponectin levels. ASC complex also promoted energy metabolism by increasing the phosphorylation of AMPK and UCP1 expression, indicative of enhanced thermogenesis and lipid oxidation. ASC complex supplementation demonstrates a potent anti-obesity effect by modulating adipogenesis, lipid metabolism, and energy expenditure. The findings suggest that ASC complex could serve as a promising natural therapeutic strategy for obesity and metabolic disorders. Further research, including clinical trials, is warranted to validate its efficacy and safety in human populations. 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

Tail adipose deposition in sheep is an economically significant trait that has an impact on meat quality and reproductive performance. This study elucidates the regulatory mechanism of FGFBP1 in the proliferation and differentiation of ovine tail-derived preadipocytes. Overexpression and knockdown methods were used to establish gain- and loss-of-function models, and the biological effects of FGFBP1 on adipocyte dynamics were systematically assessed. FGFBP1 overexpression significantly inhibited cellular proliferation by cell cycle arrest in the G2/M phase, and, at the same time, promoted adipocyte differentiation by upregulating key adipogenic markers (PPARγ, Adiponectin, C/EBPα, and FABP4). In contrast, gene silencing enhanced the proliferative capacity and decreased lipid droplet accumulation, confirming its inhibitory role in adipogenesis. Our findings indicate that FGFBP1 is a key regulator of tail adipogenesis. This discovery enhances our understanding of the mechanisms of adipocyte differentiation and provides theoretical bases and potential therapeutic targets for optimizing lipid deposition traits in livestock production. Full article

Background/Objectives: Obesity is a major health concern that can lead to various chronic diseases. Little is known about the anti-obesity effect of a standardized hot water extract from the stems of Ipomoea batatas (WIB). This study aimed to evaluate the therapeutic potential of WIB as a natural alternative to conventional anti-obesity treatments by assessing its effects on body weight, fat accumulation, and key metabolic biomarkers in a high-fat diet-induced obesity model. Methods: A high-fat diet (HFD) induced obesity in C57BL/6 mice. The mice were then treated orally with either orlistat (positive control) or WIB. Changes in body weight, food intake, and fat weight were measured, along with blood lipid profiles and adipokines. Western blot analyses were conducted to determine protein levels in each tissue. H&E staining in white adipose tissue and liver, and the gut microbiota composition were analyzed. Results: WIB treatment significantly reduced body weight and fat mass compared to the HFD group and demonstrated comparable effects to orlistat. WIB improved blood lipid profiles and adipokine levels. H&E staining revealed reduced fat accumulation in the white adipose tissue and liver. Also in those tissues, WIB restored expression levels of sterol regulatory element-binding protein-1 (SREBP-1) and CCAAT/enhancer-binding protein α (C/EBPα) and increased AMP-activated protein kinase (AMPK) phosphorylation. In brown adipose tissue, WIB enhanced AMPK phosphorylation and upregulated thermogenic-related proteins, including peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α), peroxisome proliferator-activated receptor α (PPARα), sirtuin 1 (SIRT1), uncoupling protein-1 (UCP-1), and cytochrome C oxidase subunit 4 (COX-IV). Analysis of gut microbiota revealed that WIB normalized β-diversity and reversed HFD-induced phyla imbalances (notably in Bacteroidetes, Firmicutes, and Proteobacteria). Conclusions: By reducing adiposity under the conditions tested in a murine model, improving metabolic markers, and favorably modulating gut microbiota, WIB demonstrates potential in mitigating obesity-related risks. These findings suggest that WIB may serve as a promising natural substance for the management of obesity. Further studies are warranted to confirm its efficacy and explore the potential underlying mechanisms in overweight or obese humans as a health supplement to help manage or prevent obesity. Full article

Perirenal adipose tissue (PRAT) exhibits particular morphological features, with its activity being mainly related to thermogenesis. However, an expanded PRAT area seems to play a significant role in cardiovascular diseases, diabetes mellitus, and chronic kidney disease pathogenesis. Numerous studies have demonstrated that PRAT may support cancer progression and invasion, mainly in obese patients. The mechanism underlying these processes is of dysregulation of PRAT’s secretion of adipokines and pro-inflammatory cytokines, such as leptin, adiponectin, chemerin, apelin, omentin-1, vistatin, nesfatin-1, and other pro-inflammatory cytokines, modulated by tumor cells. Cancer cells may also induce a metabolic reprogramming of perirenal adipocytes, leading to increased lipids and lactate transfer to the tumor microenvironment, contributing to cancer growth in a hypoxic milieu. In addition, the PRAT browning process has been specifically detected in renal cell carcinoma (RCC), being characterized by upregulated expression of brown/beige adipocytes markers (UCP1, PPAR-ɣ, c/EBPα, and PGC1α) and downregulated white fat cells markers, such as LEPTIN, SHOX2, HOXC8, and HOXC9. Considering its multifaceted role in cancer, modulation of PRAT’s role in tumor progression may open new directions for oncologic therapy improvement. Considering the increasing evidence of the relationship between PRAT and tumor cells, our review aims to provide a comprehensive analysis of the perirenal adipocytes’ impact on tumor progression and metastasis. Full article

The consumption of an unbalanced diet, such as a high-fat diet, is strongly associated with hyperlipidemia and significantly contributes to the development of cardiovascular and cerebrovascular diseases, which are the leading causes of death worldwide. Globally, about 17.9 million people die of cardiovascular disease each year (WHO 2023). Probiotics have emerged as a promising intervention to alleviate hyperlipidemia. Therefore, this study investigates the effects of Lactobacillus fermentum 166 (LF-166), isolated from yak yogurt in the Sichuan Tibetan area, on lipid metabolism in the liver and gut microbiota of high-fat-diet-induced hyperlipidemic mice. The results revealed that the Lactobacillus fermentum 166 (LF-166) treatment reduced the body weight and decreased the blood and liver lipid levels in these mice. Based on the histopathological findings, LF-166 could alleviate liver steatosis and colon injury. Additionally, 16S rRNA sequencing of the mice’s colonic contents showed that LF-166 reduced the Firmicutes/Bacteroidetes (F/B) value and enhanced the richness and diversity of the gut microbiota. LF-166 regulated hepatic lipid metabolism through the up-regulation of the genes Lxr, Ampkα, Fxr, Hsl, and Atgl and the down-regulation of C/ebpα and Pparγ in the liver; it also regulated intestinal lipid metabolism by up-regulating Abcg5 and Abcg8 in the ileum and down-regulating the expression of the genes Npc1l1, Asbt, and Ibabp. Thus, LF-166 may inhibit hyperlipidemia progression by modulating the expression of key genes involved in hepatic lipid metabolism, influencing the intestinal microbiota through the liver–gut axis, and regulating systemic lipid metabolism. Full article

A rise in obesity during the COVID-19 pandemic has spurred the development of safe and effective natural anti-obesity agents. In this study, we propose Rubia akane Nakai fruit extract (RFE) as a potential natural product-based anti-obesity agent. R. akane Nakai is a plant of the Rubiaceae family that grows throughout Republic of Korea. Its roots have long been used medicinally and are known for various bioactivities, but the fruit’s bioactivities are unexplored. We investigated the anti-obesity effects of RFE using 3T3-L1 adipocytes and high-fat diet-induced obese mice. In 3T3-L1 adipocytes, RFE inhibited adipogenic differentiation and lipogenesis by downregulating PPARγ (peroxisome proliferator-activated receptor γ), C/EBPα (CCAAT enhancer-binding protein α), and SREBP-1 (sterol regulatory element-binding protein 1) through AMPK (AMP-activated protein kinase) activation and by delaying the initiation of MCE (mitotic clonal expansion), which is essential for early adipogenesis. At the in vivo level, RFE improved the phenotypes of obesity and insulin resistance. In white adipose tissue, RFE not only suppressed adipogenic differentiation and lipogenesis through AMPK activation but also improved insulin sensitivity by upregulating basal GLUT4 (glucose transporter type 4) expression. Therefore, this study advances RFE as a potential natural treatment for obesity and insulin resistance. Full article

Obesity and its related diseases severely threaten people’s health, causing persistently high morbidity and mortality worldwide. The abnormal proliferation and hypertrophy of adipocytes mediate the expansion of adipose tissue, which is the main cause of obesity-related diseases. Inhibition of cell proliferation during the mitotic clonal expansion (MCE) period of adipogenesis may be a promising strategy for preventing and treating obesity. Arthrocolins are a series of fluorescent dye-like complex xanthenes from engineered Escherichia coli, with potential anti-tumor and antifungal activities. However, the role and underlying mechanisms of these compounds in adipocyte differentiation remain unclear. In this study, we discovered that arthrocolin B, a member of the arthrocolin family, significantly impeded adipogenesis by preventing the accumulation of lipid droplets and triglycerides, as well as by downregulating the expression of key factors involved in adipogenesis, such as SREBP1, C/EBPβ, C/EBPδ, C/EBPα, PPARγ, and FABP4. Moreover, we revealed that this inhibition might be a consequence of cell cycle arrest during the MCE of adipocyte differentiation, most likely by modulating the p53, AKT, and ERK pathways, upregulating the expression of p21 and p27, and repressing the expression of CDK1, CDK4, Cyclin A2, Cyclin D1, and p-Rb. Additionally, arthrocolin B could promote the expression of CPT1A during adipocyte differentiation, implying its potential role in fatty acid oxidation. Overall, our research concludes that arthrocolin B has the ability to suppress the early stages of adipocyte differentiation mainly by modulating the signaling proteins involved in cell cycle progression. This work broadens our understanding of the function and mechanisms of arthrocolins in regulation of adipogenesis and might provide a potential lead compound for treating the obesity. Full article

The interplay between oxidative stress and adipogenesis is a critical factor in the development of obesity and its associated metabolic disorders. Excessive reactive oxygen species (ROS) disrupt key transcription factors such as peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (C/EBPα), impairing lipid metabolism, promoting adipocyte dysfunction, and exacerbating inflammation and insulin resistance. Antioxidants, classified as endogenous (e.g., glutathione, superoxide dismutase, and catalase) and exogenous (e.g., polyphenols, flavonoids, and vitamins C and E), are pivotal in mitigating these effects by restoring redox balance and preserving adipocyte functionality. Endogenous antioxidants neutralize ROS and safeguard cellular structures; however, under heightened oxidative stress, these defenses are often insufficient, necessitating dietary supplementation. Exogenous antioxidants derived from plant-based sources, such as polyphenols and vitamins, act through direct ROS scavenging, upregulation of endogenous antioxidant enzymes, and modulation of key signaling pathways like nuclear factor kappa B (NF-κB) and PPARγ, reducing lipid peroxidation, inflammation, and adipocyte dysfunction. Furthermore, they influence epigenetic regulation and transcriptional networks to restore adipocyte differentiation and limit lipid accumulation. Antioxidant-rich diets, including the Mediterranean diet, are strongly associated with improved metabolic health, reduced obesity rates, and enhanced insulin sensitivity. Advances in personalized antioxidant therapies, guided by biomarkers of oxidative stress and supported by novel delivery systems, present promising avenues for optimizing therapeutic interventions. This review, “Crosstalk Between Antioxidants and Adipogenesis: Mechanistic Pathways and Their Role in Metabolic Health”, highlights the mechanistic pathways by which antioxidants regulate oxidative stress and adipogenesis to enhance metabolic health. Full article