Search Results (457)

Primula nutans Georgi, a medicinal herb used in Mongolian and Tibetan medicine for treating respiratory ailments, is a natural agent with antiobesity potential. We investigated the antiobesity and insulin-sensitizing effects of P. nutans Georgi extract (PGE) using in vitro and in vivo models. In 3T3-L1 preadipocytes, PGE inhibited adipocyte differentiation and lipid accumulation without cytotoxicity, accompanied by the reduced expression of adipogenic transcription factors (PPARG, C/EBPA, and adiponectin) and lipogenic genes (FASN, SCD1, and ACC), particularly during the early stages of adipogenesis. Similar effects were observed in primary stromal vascular cells derived from mouse inguinal white adipose tissue. PGE upregulated C/EBP homologous protein and C/EBPB and was associated with altered cell cycle progression, increased G2/M phase distribution, and the potential disruption of mitotic clonal expansion during early adipogenesis. In HFD-induced obese mice, intraperitoneal administration of PGE (10 or 30 mg/kg) significantly reduced body weight gain, white adipose tissue mass, and hepatic steatosis, independent of food intake. PGE downregulated lipogenic and proinflammatory gene expression in adipose and hepatic tissues and increased AMPK phosphorylation in white adipose tissue. PGE improved glucose tolerance and was associated with enhanced insulin sensitivity, as evidenced by reduced areas under the curve in the glucose tolerance and insulin tolerance tests and increased circulating adiponectin levels. Feature-based molecular networking identified 61 compounds from PGE. Network pharmacology analysis revealed several antiobesity targets, including PPARG and AKT1. Molecular docking analyses suggested favorable binding affinities between major compounds and metabolic regulators. Collectively, these findings suggest that PGE may suppress adipogenesis and improve metabolic parameters in obese mice, supporting its potential as a natural candidate for obesity and related metabolic disorders. Full article

The increasing demand for premium-quality meat has intensified interest in the molecular regulators that govern lipid deposition and sensory quality. Lipid metabolism, encompassing synthesis, oxidation, and storage, represents a key biological process affecting intramuscular fat content, tenderness, and flavor. G0/G1 Switch Gene 2 (G0S2) is widely recognized as an endogenous, non-competitive inhibitor of adipose triglyceride lipase. By inhibiting this key lipase, G0S2 restrains triglyceride hydrolysis and helps preserve lipid storage. Recent studies further suggest that G0S2 participates in adipocyte differentiation, mitochondrial regulation, apoptosis, and inflammatory signaling. Together, these findings indicate that G0S2 functions not only in lipolysis control but also as a multifunctional regulator of energy metabolism and cellular homeostasis. Despite its pleiotropic roles, which position G0S2 as a key integrator of lipid metabolism and cellular signaling networks, the specific roles and regulatory mechanisms by which G0S2 influences lipid metabolism and meat quality remain incompletely understood. This review summarized recent advances in G0S2-mediated lipid metabolism with emphasis on its regulatory network in livestock species. The physiological mechanisms by which G0S2 modulated lipolysis, lipid deposition, and intramuscular adipogenesis were discussed, along with nutritional, hormonal, and epigenetic factors controlling its expression. Moreover, its functional implications for meat quality improvement, marbling formation, and feed efficiency were highlighted. Understanding the molecular and regulatory features of G0S2 provided a foundation for developing genetic and nutritional strategies to optimize lipid utilization and enhance meat quality in modern animal production systems. Full article

Background/Objectives: Botanical supplements are increasingly investigated for their potential to address women’s health concerns. Compounds that modulate progesterone receptor (PR) signaling may help manage gynecologic disorders such as endometriosis, uterine hyperplasia, and preterm birth. Because PR ligands often cross-react with the glucocorticoid receptor (GR), this study examined two botanical compounds, paeoniflorin from Paeonia lactiflora (white peony root) and isoorientin from Vitex agnus-castus (chasteberry), that were identified as modulators of GR or PR signaling. Methods: Luciferase reporter assays were performed in OVCAR5, Ishikawa PR-B, and T47D A1-2 cells to evaluate GR and PR signaling. GR target gene expression was measured by qPCR. A receptor binding assay and computational docking were used to assess interaction with GR. Adipogenesis was evaluated in 3T3-L1 cells using Oil Red O staining and FABP4 protein expression by Western blot. Results: Paeoniflorin and isoorientin inhibited dexamethasone-induced GR signaling in OVCAR5 and Ishikawa PR-B cells. In T47D A1-2 cells, a variant of T47D engineered to express GR, both compounds blocked luciferase induction stimulated by progesterone; this effect was not observed in the parental line that expresses PR but lacks GR. In OVCAR5 cells, paeoniflorin or isoorientin combined with dexamethasone downregulated GILZ and DUSP1/MKP1 mRNA. Isoorientin directly bound GR, and computational analysis supported potential binding poses. Both compounds also reduced lipid accumulation during 3T3-L1 adipocyte differentiation and decreased FABP4 expression, consistent with GR antagonist activity and reduced adipogenesis. Conclusions: These findings identify paeoniflorin and isoorientin as botanical modulators that suppress GR signaling and limit GR-dependent adipogenic responses across multiple cell-based models under controlled in vitro conditions. Full article

Background: Postmenopausal osteoporosis is a common metabolic bone disorder characterized by decreased bone mass and microstructural deterioration, often accompanied by increased bone marrow adiposity and systemic fat accumulation. Kun-Ling Wan Formula (KLW) is a compound Chinese medicine clinically used for gynecological disorders, though its effects on postmenopausal osteoporosis and associated fat accumulation remain unclear. Distinct from previous herbal formulation studies that primarily focused on bone outcomes, our study uniquely integrates bone protection, marrow adiposity reduction, systemic metabolic improvement, and multi-omics mechanistic dissection in a high-fat diet-fed ovariectomized mouse model. Methods: KLW chemical composition was analyzed by UPLC-Q-TOF/MS. Ovariectomized (OVX) C57BL/6J mice fed high-fat or normal diet were treated with KLW at clinically equivalent or double doses, with estrogen and active compounds as controls. Bone microstructure was assessed by micro-CT, bone marrow fat by MRI-PDFF, and metabolism by OGTT, ITT, and metabolic cages. Network pharmacology, proteomics, molecular docking, and dynamics simulations identified core targets. C3H10T1/2 cells were used to assess osteogenic/adipogenic differentiation and mTOR pathway activation. Results: Twelve compounds were identified in KLW. In OVX mice, KLW significantly improved bone mineral density and trabecular microstructure, reduced adiposity and bone marrow fat, and enhanced glucose tolerance and insulin sensitivity. In vitro, KLW promoted osteogenesis and suppressed adipogenesis in C3H10T1/2 cells. Integrative analyses identified mTOR as a central target, with chrysophanol, pyrogallol, and apigenin showing high-affinity binding. KLW inhibited mTOR/S6K phosphorylation during differentiation, an effect reversible by leucine. Conclusions: KLW ameliorates osteoporosis and reduces fat accumulation in OVX mice by shifting mesenchymal stem cell differentiation toward osteogenesis via mTOR pathway modulation. Full article

Adipogenesis is a critical factor in causing obesity, which is a global health problem associated with metabolic disorders, such as insulin resistance and cardiovascular diseases. Natural compounds with anti-adipogenic activity may represent potential approaches for modulating adipocyte function. However, despite increasing interest in natural products, the anti-adipogenic potential of acridone alkaloids, particularly prenylated derivatives, remains largely unexplored. This study examined the effects of N-methylatalaphylline (NMA), a prenylated acridone alkaloid, on adipocyte differentiation, lipid accumulation, and glucose uptake. NMA exhibited anti-adipogenesis, particularly toward preadipocytes, and significantly reduced lipid accumulation in murine 3T3-L1 and human PCS-210-010 adipocytes at nontoxic doses (1.5–6 µM). At 3–6 µM, NMA downregulated adipogenic regulators, including PPARγ, C/EBPα, and SREBP1, along with adipogenic effectors, such as FABP4, adiponectin, LPL, PLIN1, and FAS. Mechanistic studies indicated that NMA treatment was associated with reduced phosphorylation of AKT, ERK, and p38, accompanied by cell cycle arrest and inhibition of mitotic clonal expansion. Meanwhile, activation of AMPK-ACC signaling, which may contribute to suppression of adipogenesis and reduced glucose uptake, was observed in differentiated 3T3-L1 cells after treatment with 6 µM NMA for 48 h. Additionally, molecular docking and molecular dynamics simulations suggested potential interaction between NMA and ERK1, supported by hydrogen bonding and hydrophobic contacts. Overall, these findings suggest that NMA exerts anti-adipogenic effects in vitro by modulating adipocyte proliferation, differentiation, and lipid metabolism. These findings highlight NMA as a promising acridone alkaloid scaffold for anti-adiposity applications, warranting further in vivo validation. Full article

The most common complication of active brucellosis in humans is osteoarticular injury. In the bone marrow microenvironment, mesenchymal stem cells (MSCs) can differentiate into either adipocytes or osteoblasts, and this balance is tightly regulated because an increase in adipogenesis may negatively affect bone formation and favor bone loss. The differentiation of MSCs into adipocytes or osteoblasts is tightly regulated by mechanisms that promote cell fate toward one lineage while repressing the other. Our study demonstrated that Brucella abortus infects MSCs but does not affect the deposition of organic and mineral matrix during osteoblast differentiation. However, the infection upregulates Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL) expression in osteoblasts, which may contribute to osteoclast activation and bone resorption. Conversely, B. abortus infection significantly influences adipocyte differentiation by modulating lipolysis, lipogenesis, and interactions between lipid droplets and mitochondria. This leads to increased cellular cholesterol levels and reduced intracellular triglycerides, accompanied by glycerol release. These changes result in more differentiated adipocytes and larger lipid droplets. Consequently, we observed increased IL-6 secretion and a higher leptin/adiponectin ratio. Importantly, these effects were independent of a functional type IV secretion system (T4SS), as purified Brucella DNA fully reproduced the adipogenic phenotype. Moreover, inhibition of TLR9—the primary sensor of bacterial DNA—significantly reduced the DNA-induced adipogenic response, demonstrating that adipocyte modulation is at least in part mediated through TLR9 signaling. In summary, B. abortus promotes MSC differentiation toward an inflammatory adipocyte phenotype. It involves a TLR-9-mediated DNA detection. It may contribute to osteoarticular injury and infection-associated bone resorption. Full article

Background/Objectives: To address the limitations of natural curcumin, this study focuses on the functional evaluation of structurally optimized derivatives. We aimed to elucidate structure–activity relationships (SAR) and the stage-specific molecular mechanisms of adipogenesis inhibition using an in vitro cellular assay. Methods: Four novel curcuminoids were synthesized and evaluated in 3T3-L1 preadipocytes against natural curcumin (Curcuminoid I). Efficacy and mechanisms were assessed via cell viability assays, quantitative Oil Red O staining, and time-dependent transcriptional profiling (qPCR/Western blotting) of the KLF family and master regulators. Results: SAR analysis identified Curcuminoid III (symmetric 3,5-dimethoxy-4-hydroxy) as the most potent and safe candidate, whereas Curcuminoid IV exhibited cytotoxicity. Time-course analysis revealed a distinct step-wise inhibition mechanism wherein Curcuminoid III significantly upregulated the differentiation repressor KLF2 at the immediate-early phase. This rapid modulation effectively prevented the subsequent induction of pro-adipogenic factors, including KLF9, KLF15, PPARγ, and C/EBPα, in the mid-stage (3–5 d). Consequently, the expression of the maturation marker aP2 was robustly suppressed by the late stage (5–7 d). Conclusions: The symmetric 3,5-dimethoxy-4-hydroxy substitution pattern appears to confer strong anti-adipogenic activity to Curcuminoid III. Early modulation of the KLF2–PPARγ axis at the onset of differentiation may initiate a cascading inhibitory effect throughout the adipogenic program. These findings highlight the potential of structurally optimized plant-derived bioactive compounds as regulators of metabolic cell fate. Full article

Obesity is a complex metabolic disorder associated with dyslipidemia, insulin resistance, and hepatic steatosis. Given its multifactorial nature, multi-component therapeutic strategies have attracted increasing interest, particularly herbal formulations containing diverse bioactive compounds. This study investigated the anti-obesity and hepatoprotective effects of a mixed herbal extract, JH01, composed of Curcuma longa, Achyranthes bidentata, and Polygonum multiflorum, using a screening-based analytical approach combined with experimental validation. Individual herbal extracts and their mixture were screened at 100 and 500 μg/mL in 3T3-L1 adipocytes. Based on superior anti-adipogenic efficacy, JH01 was selected for further study. Its effects were evaluated in vitro by Oil Red O staining and quantitative real-time PCR analysis of adipogenic genes, and in vivo using a high-fat diet (HFD)-induced obese mouse model, assessing body weight, serum lipid profiles, liver function markers, adipokine levels, and hepatic histology. JH01 showed markedly stronger inhibition of lipid accumulation than individual herbal components. JH01 significantly suppressed adipocyte differentiation and downregulated PPARγ, C/EBPα, and SREBP-1 expression in 3T3-L1 cells. Furthermore, JH01 modulated inflammatory cytokines and adipokine levels, as evidenced by reduced TNF-α, IL-6, and IL-1β levels and increased adiponectin levels. In HFD-fed mice, JH01 reduced body weight gain, serum triglyceride and total cholesterol levels, improved ALT and AST levels, decreased leptin concentrations, and attenuated hepatic steatosis. JH01 exerts potent anti-obesity and hepatoprotective effects through coordinated regulation of lipid metabolism and adipogenesis, supporting its potential as a multi-herbal therapeutic strategy for obesity-related metabolic disorders. Full article

Background: Excessive abdominal fat deposition is a major challenge in the chicken farming industry, making it essential to elucidate the molecular mechanisms underlying chicken adipogenesis. Nuclear Respiratory Factor 1 (NRF1) has been reported to suppress chicken adipogenesis by downregulating peroxisome proliferator-activated receptor gamma (PPARγ) expression. Protein Phosphatase 1 Catalytic Subunit Gamma (PPP1CC) is a multifunctional phosphatase involved in various biological processes; however, its role in chicken adipogenesis remains unclear. Objective: This study aimed to investigate the functional role and underlying mechanism of PPP1CC in chicken preadipocyte differentiation. Methods: Co-immunoprecipitation (Co-IP) and immunofluorescence assays were performed to determine the interaction between PPP1CC and NRF1 in DF1 cells. Bioinformatic analysis predicted potential NRF1 dephosphorylation sites targeted by PPP1CC, based on which NRF1 mutants mimicking dephosphorylation were constructed. Phos-tag SDS-PAGE combined with Western blot analysis were used to verify PPP1CC-mediated dephosphorylation of wild-type NRF1. Dual-luciferase reporter assays were used to evaluate the effect of PPP1CC-mediated dephosphorylation on NRF1-regulated PPARγ P1 promoter transcriptional activity. ChIP-qPCR was employed to assess the occupancy of NRF1 to the PPARγ P1 promoter upon PPP1CC overexpression. The effect of PPP1CC overexpression was assessed on preadipocyte differentiation using Oil Red O staining and marker gene expression analysis. Results: PPP1CC interacted with NRF1 in both the cytoplasm and nucleus of DF1 cells. Overexpression of PPP1CC significantly promoted NRF1 dephosphorylation during oleic acid-induced preadipocyte differentiation and increased endogenous NRF1 expression. Moreover, dual-luciferase assays showed that while PPP1CC strengthened the inhibitory effect of wild-type NRF1 on PPARγ P1 promoter transcriptional activity, it exerted no additional suppression on the already low activity mediated by the dephosphorylation-mimicking NRF1 mutants. Consistently, ChIP-qPCR results demonstrated that PPP1CC overexpression enhanced the occupancy of NRF1 to the PPARγ P1 promoter. Functional assays revealed that PPP1CC overexpression significantly inhibited chicken preadipocyte differentiation. Conclusions: PPP1CC interacts with NRF1 and promotes its dephosphorylation, enhancing NRF1-mediated suppression of PPARγ transcription and ultimately inhibiting chicken preadipocyte differentiation. These results identify the PPP1CC–NRF1–PPARγ regulatory axis and provide a potential molecular target for controlling fat deposition in broiler chickens. Full article

(1) Heterotopic ossification (HO) is a pathological process characterized by ectopic bone formation in soft tissues, often following trauma or neurological injury, and is associated with spasticity and chronic inflammation. Mesenchymal stem cells (MSCs) play a central role in HO by differentiating into osteoblasts through endochondral or intramembranous ossification, while alternative fates such as adipogenesis are suppressed. In this study, we investigated the effects of two commonly used antispastic drugs, baclofen and tizanidine, on MSC differentiation under adipogenic and inflammatory conditions in vitro. (2) Mouse C3H10T1/2 MSCs were cultured and induced toward adipogenesis in the presence of baclofen or tizanidine, and inflammatory stimuli (Interleukin-1β or lipopolysaccharides) were applied where indicated. Gene expressions of adipogenic and osteochondrogenic markers were assessed by RT-qPCR, while osteopontin protein levels were quantified by Simple Western. (3) Baclofen treatment significantly inhibited adipogenic gene expression and promoted osteochondrogenic markers and osteopontin protein under basal conditions, whereas tizanidine had minimal effects. Under inflammatory conditions, baclofen partially suppressed adipogenesis but did not strongly induce osteochondrogenesis. (4) These findings indicate that baclofen can directly modulate MSC fate, potentially contributing to HO risk, while tizanidine may offer a safer alternative for spasticity management in patients at risk of ectopic bone formation. Full article

During aging, bone marrow stromal (a.k.a. mesenchymal stem) cells (BMSCs) shift their lineage commitment away from osteogenesis and towards adipogenesis, resulting in bone loss and marrow fat accumulation. We previously reported that during osteogenesis, BMSCs activate mitochondrial oxidative phosphorylation (OXPHOS) at least in part by downregulating cyclophilin D (CypD) expression and, consequently, mitochondrial permeability transition pore (MPTP) activity. We also reported that in contrast, during adipogenesis, BMSCs upregulate CypD and MPTP, activate glycolysis and inhibit OXPHOS. To further study the role of CypD in BMSC bioenergetics, adipogenesis and bone marrow fat accumulation, we used CypD loss-of-function (LOF) or gain-of-function (GOF) models in osteo-adipoprogenitors in vitro and in vivo. We found that CypD LOF and GOF are associated with impaired and enhanced BMSC adipogenesis, respectively, both in vitro and in ectopic bone grafts in vivo. In addition, bioenergetic profiling and metabolomic analyses show evidence of corresponding metabolic reprogramming in CypD LOF and GOF cells. In summary, our study demonstrates the role of CypD-regulated mitochondrial metabolism during BMSC adipogenesis, facilitating the understanding of stem cell fate determination and the molecular mechanism of age-related bone loss as well as bone marrow fat accumulation. Full article

Obesity is well-known as a major risk factor for metabolic disorders, and natural compounds are being explored as alternatives to conventional therapies. While Centella asiatica is well known for its medicinal and dietary benefits, the biological activities of Giant Centella asiatica (GCA), especially when extracted with mineral-rich lava seawater, remain poorly characterized. This study aimed to evaluate the anti-adipogenic and lipid-metabolism-regulating effects of a novel GCA extract (GCA-LS-90) and its ability to stimulate GLP-1 secretion in vitro. GCA-LS-90 significantly inhibited lipid accumulation in 3T3-L1 adipocytes by up to 24.3% at 200 µg/mL (p < 0.001). It downregulated adipogenic transcription factors (C/EBPβ, C/EBPα, PPARγ) and lipogenic regulators (SREBP1c, FAS, G6PD, ME), while upregulating KLF2 (all p < 0.001). Western blotting confirmed reduced SREBP1c and SREBP2 protein expression, increased phosphorylation of AMPKα/ACC, and enhanced HSL activity (p < 0.05–0.001). In STC-1 cells, GCA-LS-90 increased GLP-1 secretion (53.5 pmol/L at 90 µg/mL vs. 41.3 pmol/L in control, p < 0.001). The major compounds, 3,5- and 4,5-di-O-caffeoylquinic acids, reproduced these effects. In conclusion, GCA-LS-90 modulated adipogenesis-, lipid-metabolism-, and GLP-1 secretion-related pathways in vitro, suggesting its potential as a functional ingredient for obesity management. Further in vivo studies are needed to confirm efficacy and translational relevance. Full article

Background/Objectives: Bone marrow adipose tissue (BMAT) serves multiple physiological roles but accumulates with age, compromising skeletal health. This expansion is largely driven by an adipogenic drift of bone marrow mesenchymal stromal cells (BMSCs), shifting attention toward stromal cell fate regulation as a target to preserve bone marrow homeostasis. Preventing adipogenic commitment may be as relevant as directly inducing osteogenesis for maintaining a bone-permissive marrow microenvironment. Here, we investigated whether olive leaf extract (OLE) and its purified secoiridoid components, oleacin (OC) and oleuropein aglycone (OA), modulate the adipogenic differentiation and proliferative capacity of human BMSCs. Methods: Human BMSCs were induced to undergo adipogenic differentiation and treated with OLE, OC, or OA. Intracellular lipid accumulation and the expression of key adipogenic regulators were assessed. Proliferative capacity was evaluated under both maintenance and adipogenic conditions. Results: Under adipogenic conditions, OLE markedly reduced intracellular lipid accumulation and induced a coordinated downregulation of PPARγ, PLIN1, FABP4, ADIPOQ, LEP and the adipogenesis-associated miR-422a. In contrast, OC and OA exerted more selective and specific effects on biomarkers, indicating the partial and complementary modulation of adipogenic programs. Notably, OLE also increased BMSC proliferation under both maintenance and adipogenic conditions, suggesting the preservation of a less committed stromal cell pool. Although the relative contribution of enhanced proliferation versus the direct inhibition of adipogenic pathways cannot be fully disentangled, the combined molecular and functional data support a dual action of OLE on stromal cell fate. Conclusions: OLE limits adipogenic commitment while maintaining stromal cell proliferative competence, processes that are critically involved in BMAT expansion and bone marrow dysfunction. OC and OA contribute to OLE bioactivity deserving further investigation, particularly in combination, as potential modulators of BMAT expansion. Full article

Terminalia bellirica extract (TBE) has long been utilized in Ayurvedic medicine across Indian and surrounding regions for diverse therapeutic applications. Despite its traditional prominence, systematic investigations addressing the anti-obesity efficacy and underlying mechanisms remain limited. In this study, we evaluated the anti-obesity potential of TBE using both 3T3-L1 adipocyte and high-fat diet (HFD)-induced mice model. In vitro studies using 3T3-L1 adipocytes demonstrated that TBE significantly inhibited lipid accumulation and downregulated key genes involved in adipogenesis and lipogenesis, while upregulating genes promoted lipolysis and energy metabolism. To validate these cellular effects in a physiological context, mice were randomly assigned to six groups: normal control (NC), HFD-induced obese (C), HFD with metformin (100 mg/kg b.w., PC), and HFD with TBE at 50, 100, and 200 mg/kg b.w. Consistent with the in vitro findings, TBE supplementation significantly reduced body weight gain, adipose tissue mass, and adipocyte size in HFD-induced obese mice. Taken together, these results indicate that TBE exerts anti-obesity effects through modulation of adipose tissue metabolic pathways, highlighting its therapeutic potential for obesity management. Full article

Obesity is associated with numerous pathological processes in the body, including inflammation, oxidative stress, and consequently, mitochondrial dysfunction. In recent years, research in anti-obesity therapy has also focused on the function of adipocytes and the inhibition of adipogenesis. In this study, we investigated the effect of the well-known flavonoid quercetin on mitochondrial function, apoptosis and differentiation of human preadipocytes. The Chub-S7 cell line model was used in the in vitro studies. Mitochondrial function was measured by oxygen consumption rates, intracellular ATP content, mitochondrial membrane potential, apoptosis assay (Annexin-5, caspase-9 activity), and ROS generation. Chub-S7 cell differentiation was assessed by Oil Red O staining. The results showed that the quercetin inhibited differentiation of human Chub-S7 preadipocytes and reduced fat accumulation in lipid droplets. Additionally, quercetin influenced mitochondrial biogenesis and mitochondrial uncoupling by changes in mitochondrial respiratory states and also increased mitochondrial membrane potential. Quercetin decreased routine respiration, R/E and netROUTINE control ratio. Our results demonstrate that quercetin is a dietary component that may modulate mitochondrial bioenergetics and inhibit adipogenesis. If these results were confirmed in in vivo studies, quercetin could be considered a factor used to prevent obesity. Full article