Search Results (232)

(1) Background: Perfluorodecanoic acid (PFDA), a persistent perfluoroalkyl obesogen, promotes adipogenesis, yet whether its effects can be pharmacologically opposed remains unknown. (2) Methods: We examined the interaction between PFDA (50, 75 μM) and the dietary polyphenol curcumin (20, 30 μM) throughout the 8-day 3T3-L1 preadipocyte differentiation protocol, using cell-viability (WST-1) assays with a two-factor interaction analysis, Oil Red O lipid quantification and mRNA profiling of Pparg, Cebpa, Srebf1, and Fasn. (3) Results: PFDA alone increased lipid accumulation and upregulated Pparg, Cebpa, and Fasn, whereas Srebf1 was induced only weakly and only at the higher dose, a pattern compatible with preferential engagement of the PPARγ/C/EBPα program over the SREBP-1c lipogenic pathway at the mRNA level, although the transcripts were not formally compared and no protein-level data were obtained. At two sub-cytotoxic concentrations, curcumin preserved potent antiadipogenic activity, reducing lipid accumulation by up to 67.3% and reversing PFDA-induced gene upregulation. At the viability endpoint the two compounds acted independently: curcumin significantly reduced viability and PFDA significantly increased it, with no statistically detectable interaction between them (two-way ANOVA, interaction p = 0.85). (4) Conclusions: This dissociation shows that a chemical interaction defined at one biological endpoint does not predict its outcome at another, a principle with broad implications for mixture toxicology—and it establishes curcumin as a candidate dietary intervention that intercepts an obesogen’s transcriptional program against environmentally driven metabolic disruption. Full article

Homeodomain-interacting protein kinase 2 (HIPK2) is an important regulator of various transcription factors and cofactors, which are involved in cell growth, cell death, and embryonic development. Previously, it has been reported that HIPK2 is upregulated during white fat development. However, the expression and functional role of HIPK2 during adipogenesis remain unclear. Here, we investigated the expression and biological function of HIPK2 during the adipogenesis of 3T3-L1 cells. Importantly, protein and mRNA expression of HIPK2 were significantly upregulated in a time-dependent manner during 3T3-L1 preadipocyte differentiation. Notably, distinct pharmacological inhibitors revealed the pivotal roles of p38 MAPK and PKC in the induction of HIPK2 expression during differentiation of 3T3-L1 cells. Moreover, knockdown of HIPK2 significantly reduced lipid storage and triglyceride (TG) levels without cytotoxicity during 3T3-L1 preadipocyte differentiation. At the mechanistic level, HIPK2 knockdown reduced the expression of CCAAT/enhancer-binding protein-α (C/EBP-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), fatty acid synthase (FAS), perilipin A, leptin, and resistin, as well as the phosphorylation of signal transducer and activator of transcription-3 (STAT-3) during 3T3-L1 preadipocyte differentiation. Taken together, these results revealed that HIPK2 expression is significantly upregulated in p38 MAPK- and PKC-dependent manners, and this upregulation of HIPK2 plays a critical role in lipid accumulation during differentiation of 3T3-L1 cells, which is mediated by control of the expression and phosphorylation levels of C/EBP-α, PPAR-γ, STAT-3, FAS, and perilipin A. Full article

Obesity and its associated metabolic disorders drive the search for natural compounds with anti-adipogenic properties. This study evaluated Vitis vinifera seed extract (GE), rich in oligomeric proanthocyanidins (OPCs), and Allium sativum bulb extract (ALL), rich in thiosulfinates, for their effects on adipogenesis and COX-related prostanoid modulation in 3T3-L1 cells. Differentiating preadipocytes were treated with non-cytotoxic concentrations of GE, ALL, or their combination (AGE) at a 1:600 dilution (approximately 23 μg/mL allicin and 0.05% OPCs). Lipid accumulation was assessed by Oil Red O staining, prostanoid levels (PGE₂, TXA₂, and PGI₂) were quantified by enzyme immunoassay, and adipogenic gene expression (PPARγ, CEBPα and GLUT4) was analyzed by RT-qPCR. All treatments reduced lipid accumulation, with GE showing the most potent inhibition (68.0% of control), followed by ALL (81.6%) and AGE (78.0%). Distinct prostanoid patterns emerged: GE increased both PGE₂ and PGI₂ and decreased TXA₂, while ALL increased PGE₂ and reduced both TXA₂ and PGI₂. The combination (AGE) did not enhance the anti-adipogenic effects. At the molecular level, GE downregulated PPARγ, CEBPα, and GLUT4, whereas ALL did not affect their transcription, indicating distinct mechanisms. These findings demonstrate that GE and ALL inhibit adipogenesis through differential modulation of the COX pathway and gene expression, highlighting their potential as functional ingredients for obesity management. The lack of synergy in the combination warrants further investigation. Full article

Obesity is a major metabolic disorder characterized by excessive lipid accumulation and adipocyte differentiation. The mitogen-activated protein kinase kinase 5 (MEK5) signaling pathway has been implicated in diverse cellular processes; however, its role in adipogenesis remains incompletely understood. In this study, we investigated the anti-adipogenic effects of BIX02189, a selective MEK5 inhibitor, using 3T3-L1 adipocytes, human adipose-derived stem cells (hASCs), and zebrafish models. Treatment with BIX02189 significantly reduced lipid accumulation and triglyceride content during adipocyte differentiation in a dose-dependent manner without marked cytotoxicity. BIX02189 effectively suppressed MEK5 phosphorylation and downregulated the expression of key adipogenic transcription factors, including peroxisome proliferator-activated receptor gamma (PPAR-γ) and CCAAT/enhancer-binding protein alpha (C/EBP-α). In addition, BIX02189 decreased the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and STAT5, as well as the expression of lipogenic markers such as fatty acid synthase (FAS), perilipin A, and leptin. Conversely, BIX02189 enhanced AMP-activated protein kinase (AMPK) phosphorylation and markedly reduced the protein and mRNA expression of acetyl-CoA carboxylase (ACC), a key enzyme involved in fatty acid synthesis. Similar anti-adipogenic effects were observed in hASCs. Furthermore, BIX02189 significantly attenuated lipid accumulation in a zebrafish obesity model without affecting body length or causing overt toxicity. Collectively, these findings demonstrate that pharmacological inhibition of MEK5 suppresses adipogenesis and lipid accumulation through regulation of the STAT3/STAT5–PPAR-γ axis and activation of AMPK signaling. These findings provide the first evidence that MEK5 inhibition exerts anti-adipogenic effects in adipocytes and zebrafish, highlighting the MEK5 signaling pathway as a previously unrecognized regulator of adipogenesis and lipid metabolism. Full article

Marine halophytes are gaining attention as a source of plant-derived bioactive compounds with potential applications across nutraceuticals, functional foods, and preventive nutrition. Among them, Salicornia europaea L. is a coastal succulent whose adaptation to hypersaline environments shapes a distinctive phytochemical profile of pharmacological interest. This narrative review integrates current evidence on the bioactive composition, mechanistic activities, and translational relevance of S. europaea and related Salicornia species. Their secondary metabolome includes flavonols, isorhamnetin glycosides, hydroxycinnamic acids, oleanane-type triterpene saponins, fermentable polysaccharides, carotenoids, and a mineral-rich ionic matrix. Reported activities span antioxidant, anti-inflammatory, vascular-protective, anti-adipogenic, glycaemic-modulating, antimicrobial, and microbiome-related effects, mediated through pathways involving NF-κB, PPAR-γ, endothelial nitric oxide signalling, and short-chain fatty acid production. Beyond its individual phytochemical components, the matrix as a whole may also support sodium-reduction strategies in food formulation, providing a complementary nutritional rationale for its incorporation as a functional ingredient. Despite a coherent body of mechanistic and preclinical findings, clinical evidence remains limited, particularly regarding long-term efficacy, dose standardisation, and bioavailability in humans. Future work should prioritise adequately powered intervention trials and standardised characterisation of marine halophyte bioactives to clarify their evidence-based role in functional food development and future precision nutrition applications. Full article

Daidzin is a soy-derived isoflavone with reported anti-obesity effects; however, the biological activity of microbial-derived daidzin remains poorly understood. In this study, we investigated the anti-adipogenic and anti-obesity potential of microbial-derived daidzin (hereafter referred to as Eco-3) in both in vitro and in vivo models. Eco-3 significantly suppressed adipocyte differentiation and lipid accumulation in 3T3-L1 preadipocytes and human adipose-derived stem cells (hASCs) without inducing cytotoxicity. Mechanistically, Eco-3 reduced the expression of key adipogenic regulators, including PPAR-γ and C/EBP-α, and modulated lipid metabolism-related proteins such as FAS and perilipin A. In addition, Eco-3 activated AMPK signaling while inhibiting the STAT-3 and STAT-5 pathway. In zebrafish models, Eco-3 significantly reduced lipid accumulation under both normal and diet-induced obesity conditions, as demonstrated by LipidGreen2 and Oil Red O staining. Collectively, these findings suggest that Eco-3 exerts anti-obesity effects through coordinated regulation of adipogenesis and lipid metabolism. Full article

Adipogenesis is one way by which adipose tissue expands in our body. It is a complex tightly regulated process involving differentiation of mesenchymal stem cells (MSCs) into mature, lipid-containing adipocytes. One of the byproducts of this mechanism is leptin, an adipokine that plays a pivotal role in regulating food intake and energy homeostasis. While the increase in leptin secretion in proportion to fat mass expansion shows that leptin functions as a downstream marker of adipogenesis, emerging studies suggest that leptin itself may influence the adipogenesis process and act as a regulator. However, despite much research done to explore this, its role remains incompletely understood and often contradictory, with studies reporting pro-adipogenic, anti-adipogenic, or neutral effects depending on experimental context. These discrepancies highlight the influence of factors such as leptin concentration, timing of exposure, cell type, adipose depot, and species differences. This review gathers current evidence on leptin’s role in adipogenesis, integrating findings from diverse experimental models and biological systems. We further examine the underlying molecular mechanisms and signaling pathways involved, aiming to clarify the context-dependent effects of leptin and identify key knowledge gaps to guide future research in adipose tissue biology and metabolic disease. Full article

Ononis spinosa L. (Fabaceae), commonly known as spiny restharrow, is a widely distributed medicinal plant traditionally used in European and Middle Eastern phytotherapy, particularly for the management of urological and inflammatory conditions. Despite its long-standing ethnomedicinal relevance, comprehensive syntheses of its phytochemical profile and biological activities remain limited. This review aimed to summarize current evidence regarding the chemical constituents and pharmacological effects of O. spinosa. Four electronic databases (PubMed, Scopus, Web of Science, and SpringerLink) were searched for studies published between 1997 and 2024. The search yielded 308 records; after duplicate removal and eligibility screening, 34 studies met the inclusion criteria. The phytochemical profile of O. spinosa is characterized predominantly by isoflavonoids (e.g., ononin and other formononetin derivatives), triterpenes, phenolic acids, and additional polyphenolic compounds. Although the phytochemical profile of O. spinosa includes multiple classes of secondary metabolites, this review places particular emphasis on phenolic compounds, given their prevalence and well-documented biological activities. Experimental evidence indicates a broad spectrum of biological activities, including anti-inflammatory effects (associated with cPLA2α inhibition and cytokine modulation), antibacterial and antifungal activity, antioxidant capacity, wound-healing and dermatological benefits, as well as diuretic and anti-adhesive effects in urinary models. Additional reported properties include antiproliferative, anti-adipogenic, analgesic, and neurotrophic activities. Proposed mechanisms of action involve enzyme inhibition (e.g., Hyal-1 and COX-2), modulation of transient receptor potential (TRP) channels, redox regulation, and interference with microbial adhesion and inflammatory signaling pathways. Overall, O. spinosa contains bioactive compounds exhibiting a wide range of pharmacological activities supported by in vitro and in vivo studies. Among the investigated effects, anti-inflammatory, urological, and wound-healing activities appear to be the most promising targets for future research. These findings highlight its therapeutic potential while emphasizing the need for well-designed clinical studies to further validate its medicinal applications. 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

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

Background/Objectives: Obesity represents a critical risk factor for various chronic illnesses and metabolic dysfunctions, underscoring the urgency of identifying safe, food-based interventions to curb fat over-accumulation. Mesona procumbens Hemsl. (Hsian-tsao) is a traditional Chinese herb known for its antioxidant and health-promoting properties; however, it remains unclear how its phenolic acid profiles contribute to anti-obesity activity. This research explored the anti-adipogenic potential of various Hsian-tsao ethanol extracts, focusing on how their phenolic profiles influence lipid suppression in 3T3-L1 adipocytes. Methods: Ethanol extracts prepared using different ethanol concentrations were analyzed for total polyphenol content, antioxidant capacity, and phenolic acid profiles. Adipocytes were exposed to 0, 100, and 250 μg/mL of Hsian-tsao ethanol extract for 48 h duration to monitor changes in cell count and intracellular triglyceride levels. Results: Among all fractions, the 40% ethanol extract (40EEHT) possessed the most robust antioxidant capacity and highest polyphenol content, specifically showing enriched levels of caffeic acid, p-coumaric acid, and total phenolic acids. Notably, while 40EEHT influenced cell density at certain concentrations, it significantly and specifically reduced intracellular triglyceride content, indicating a potent inhibitory effect on lipid storage independent of changes in cell number. Comparative analysis using phenolic acid standards revealed that caffeic acid exerted the strongest inhibitory effect on lipid accumulation, suggesting that it is a key contributor to the anti-adipogenic activity of 40EEHT. Conclusions: Collectively, these findings demonstrate that phenolic acid profiles, particularly caffeic acid enrichment, critically contribute to the potential anti-adipogenic effects of specific ethanol extracts of M. procumbens. Therefore, Hsian-tsao ethanol extracts represent a promising natural source for the development of functional ingredients targeting obesity and related metabolic disorders. 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

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

Proanthocyanidins (PACs) are a key group of bioactive phytochemicals known to provide health benefits. Most PACs are non-bioavailable polymeric molecules that need to be biotransformed by colonic microbes into simple metabolites to exert their pharmacological effects. In this study, six previously unexamined PAC metabolites from Saccharomyces cerevisiae, 3-aminophenol (3-AMP), 3-aminosalicylic acid, 2,4-dihydroxy-6-methylbenzaldehyde, 4-hydroxyphenylacetamide (4-HPA), 3-phenyllactic acid, and 2,4,6-trihydroxyacetophenone, were tested for their antiadipogenic activity using an insulin-dependent 3T3-L1 preadipocyte differentiation model. Lipid accumulation in differentiating preadipocytes was visualized and measured with the Oil Red O assay. Only 3-AMP and 4-HPA significantly reduced lipid accumulation at a concentration of 25 µM. To understand the cellular mechanisms, protein levels of key regulators of adipogenesis and lipid metabolism were analyzed using Western blotting. 3-AMP and 4-HPA may attenuate lipid accumulation by suppressing de novo lipogenesis, with 3-AMP downregulating the peroxisome proliferator-activated receptor (PPAR)-γ/acetyl-CoA carboxylase (ACC)/fatty acid synthase (FAS) axis and 4-HPA primarily inhibiting ACC/FAS signaling. Molecular docking studies indicated that 3-AMP may downregulate PPAR-γ expression through competitive inhibition of insulin receptors. These preliminary findings suggest that 3-AMP and 4-HPA exhibit potential antiadipogenic effects, highlighting PAC-derived postbiotics as promising nutraceuticals for mitigating obesity risk. Full article

A species of the genus Tetracera has been used as herbal medicine in traditional Indian Tetracera loureiri medicine. Tetracera loureiri, a plant from the Dilleniaceae family is considered one of the most valuable herbs in Thailand and is native to Southeast Asia. However, the anti-obesity effects of Tetracera loureiri extract have not been reported. In this study, we screened the effect of EtOH extract on lipid accumulation in a 3T3-L1 adipocyte model at various concentrations using Oil Red O staining, and the results were visualized under a light microscope. The fractionation of the soluble CH₂Cl₂ and EtOAc fractions from the EtOH extract revealed that both fractions significantly inhibited lipid accumulation in adipocytes at 2.5, 5, and 10 μg/mL, compared to n-hexane, n-BuOH, and aqueous extracts. Bioactivity-guided fractionation of the CH₂Cl₂ and EtOAc extract led to the phytochemical investigation of 10 secondary metabolites (1–10), and the structure of these compounds was identified using various spectroscopic methods. All isolated compounds were evaluated for their ability to inhibit adipogenesis at a concentration of 2.5, 5, and 10 μM compared with positive control (Orlistat 100 μg/mL); in particular, compounds 1–3, 5, and 7–8 showed 57.39 ± 6.98, 19.35 ± 4.53%, 75.81 ± 1.75%, 17.61 ± 1.62%, 19.83 ± 5.27 and 14.66 ± 3.85% reduction in fat accumulation at 10 μMm in 3T3-L1 adipocytes, respectively. The activity of these compounds also inhibited the secretion of adiponectin and leptin in 3T3-L1 adipocytes, suggesting their role in disrupting adipocyte function and metabolic regulation. Therefore, the results herein provide experimental evidence supporting the potential of Tetracera loureiri extracts as an anti-obesity therapeutic agent. Full article