Search Results (132)

Excessive manganese (Mn) exposure is associated with neuroinflammation and cognitive impairment, yet the contribution of endogenous pro-resolving pathways to Mn neurotoxicity remains incompletely understood. Here, we examined the involvement of the lipocalin-type prostaglandin D synthase (L-PGDS)/15-deoxy-Δ^12,14-prostaglandin J2 (15d-PGJ2) pathway using Mn-treated male C57BL/6J mice, BV2 microglia, and SH-SY5Y neurons, together with data from occupationally Mn-exposed workers (cross-sectional, hypothesis-generating). In the occupational cohort, circulating 15d-PGJ2 levels and L-PGDS expression were reduced following Mn exposure, consistent with the experimental findings. PPI network analysis and promoter prediction highlighted C/EBPβ and MMP9 as potential mediators of Mn-induced neuroinflammatory responses. Consistent with these observations, Mn exposure increased C/EBPβ and MMP9 expression, promoted M1 microglial polarization, elevated ROS production, and aggravated neuronal injury in a microglia–neuron co-culture system. Knocking down either C/EBPβ or MMP9 attenuated inflammatory activation and oxidative stress and reduced neuronal damage. Administration of exogenous 15d-PGJ2 suppressed Mn-induced increases in C/EBPβ and MMP9, alleviated inflammatory and oxidative responses, and partially ameliorated cognitive impairment in Mn-exposed mice. Transcriptomic analyses further showed that 15d-PGJ2 counteracted a substantial proportion of Mn-induced transcriptional alterations, particularly those related to inflammatory and neurodevelopmental processes. In addition, Ptgds knockdown reduced endogenous 15d-PGJ2 production and increased MMP9 expression, whereas exogenous 15d-PGJ2 largely reversed these changes. Together, these findings support the involvement of L-PGDS/15d-PGJ2 pathway dysregulation in Mn-induced neuroinflammation and suggest that restoration of 15d-PGJ2 signaling may represent a potential therapeutic approach for Mn-associated neurotoxicity. Full article

Excessive adipose tissue expansion contributes to metabolic dysfunction, highlighting the need to identify compounds that restrain adipocyte differentiation without causing nonspecific cytotoxicity. This study investigated whether 2-O-methylhonokiol suppresses adipogenesis in 3T3-L1 preadipocytes and examined its effects on adipogenic transcription, metabolic signaling, ER stress-related responses, kinase activity, and early cell cycle progression. 3T3-L1 cells were induced to differentiate with an MDI cocktail and treated with 25 or 50 µM 2-O-methylhonokiol during differentiation. Lipid accumulation was evaluated by Oil Red O staining, protein expression and phosphorylation were analyzed by immunoblotting, cell cycle distribution was assessed 24 h after MDI induction, and basal viability was measured using the CCK-8 assay. 2-O-methylhonokiol markedly reduced neutral lipid accumulation and suppressed key adipogenic regulators and maturation markers, including C/EBPβ, PPARγ, C/EBPα, FABP4, and FASN. At the signaling level, 2-O-methylhonokiol increased AMPKα phosphorylation without altering total AMPKα and reduced FASN expression, whereas mTOR phosphorylation was reduced at 50 µM. These findings suggest that 2-O-methylhonokiol is associated with metabolic and lipogenic signaling remodeling during adipocyte differentiation. 2-O-methylhonokiol also modified kinase-associated responses, increasing AKT and JNK phosphorylation while reducing the detectable phosphorylated ERK signal, with total AKT, ERK, and JNK remaining largely unchanged. ER stress-related signaling displayed a selective profile, characterized by increased IRE1α expression, XBP1s induction, elevated p-eIF2α, unchanged total eIF2α, and no compensatory increase in GRP78. During early adipogenesis, 2-O-methylhonokiol attenuated MDI-induced cell cycle redistribution by preserving a larger G0/G1 population and limiting progression toward later cell cycle phases, consistent with impaired mitotic clonal expansion. These effects occurred at concentrations that did not significantly reduce basal cell viability. Overall, 2-O-methylhonokiol suppresses 3T3-L1 adipogenesis by reducing adipogenic and lipogenic execution, accompanied by AMPK-associated metabolic remodeling, kinase signaling changes, selective ER stress-related responses, and restriction of early cell cycle progression. Further pathway-specific studies are required to define the causal contribution of each signaling axis. Full article

Cardiac arrest followed by cardiopulmonary resuscitation (CA/CPR) induces systemic ischemia and frequently results in acute kidney injury (AKI). The ketone body β-hydroxybutyrate (BHB) maintains mitochondrial and peroxisomal homeostasis through activation of the C/EBPβ–Pck1 axis, whereas Pck1 preserves mitoribosome integrity and mtDNA-encoded oxidative phosphorylation (OXPHOS) translation. However, it remains unclear whether this pathway is disrupted during CA/CPR-induced AKI and whether empagliflozin can restore its activity. Male C57BL/6J mice and proximal tubule-specific Pck1 conditional knockout (CKO) mice were subjected to short-duration or standard CA/CPR protocols. Empagliflozin was administered orally for 7 days before CA/CPR induction. Circulating BHB levels, renal expression of C/EBPβ and Pck1, and markers of mitochondrial, peroxisomal, and mitoribosomal abundance and function were evaluated using established methods. CA/CPR markedly reduced circulating BHB levels and suppressed the C/EBPβ–Pck1 signaling axis. These changes were accompanied by depletion of peroxisomal markers, mitochondrial regulators, and mitoribosomal components as well as increased tubular apoptosis and albuminuria. Pck1 CKO mice exhibited severe organelle dysfunction and aggravated renal injury. In contrast, empagliflozin restored BHB levels, preserved C/EBPβ and Pck1 expression, and maintained mitochondrial, peroxisomal, and mitoribosomal integrity, thereby attenuating tubular injury and albuminuria. Notably, empagliflozin treatment increased BHB, C/EBPβ, and Pck1 levels in noninjured mice without inducing organelle expansion, suggesting that Pck1 activation alone is insufficient to promote mitoribosome biogenesis under basal conditions. Collectively, these findings demonstrate that empagliflozin protects against CA/CPR-induced AKI and identify Pck1 as a key metabolic regulator linking ketone signaling to organelle resilience. 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: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is the most prevalent chronic liver disorder globally. Mazdutide has shown clinical benefits in weight management and metabolic regulation, indicating its potential as a therapeutic agent for MASLD. This study aimed to investigate the efficacy and mechanism of action of Mazdutide against early-stage MASLD. Methods: A MASLD mouse model was induced by a 12-week high-fat diet, followed by a 4-week treatment with subcutaneous Mazdutide (100, 200, or 400 μg/kg). In vitro, a cellular MASLD model was established by treating hepatocytes with 1 mM free fatty acids for 24 h, followed by co-treatment with Mazdutide (10, 20, or 50 nM) or the endoplasmic reticulum (ER) stress inhibitor 4-phenylbutyric acid (4-PBA). Serum and hepatic lipid profiles, liver injury markers, and pro-inflammatory cytokines were quantified. Liver histopathology was assessed by hematoxylin and eosin and Oil Red O staining. Protein expression related to ER stress, inflammation, and lipid metabolism was analyzed by immunohistochemistry and Western blot. Results: Compared with the MASLD model group, Mazdutide treatment significantly ameliorated systemic and hepatic lipid metabolism disorders, reduced liver injury markers and hepatic steatosis, and mitigated inflammation and oxidative stress in MASLD mice and hepatocytes (p < 0.05). Mechanistically, Mazdutide alleviated ER stress by modulating the protein kinase R-like endoplasmic reticulum kinase (PERK) pathway, suppressed the nuclear Factor kappa B (NF-κB)-mediated inflammatory response, and downregulated the expression of key lipogenic regulators including sterol regulatory element-binding protein 1 (SREBP-1), CCAAT/enhancer-binding protein beta (C/EBPβ), and peroxisome proliferator-activated receptor gamma (PPARγ) in both models (p < 0.05). Conclusions: Our findings demonstrate that Mazdutide alleviates hepatic ER stress in MASLD, suppresses inflammatory responses and improved lipid metabolism, which ultimately attenuates disease progression. Full article

Background: As a key contributor to metabolic disorders, obesity is recognized as a critical global health challenge. Adipocyte differentiation depends on the mitotic clonal expansion (MCE) phase, which is controlled by oxidative balance and transcription factors like C/EBPβ. Sesaminol, a lignan derived from Sesamum indicum, has potent antioxidant properties. This study aimed to investigate whether sesaminol suppresses adipogenesis by modulating ROS signaling, MCE, and the Nrf2-ARE pathway. Methods: In the early period of adipogenic induction, 3T3-L1 preadipocytes received treatment with sesaminol. Adipogenic development was evaluated through Oil Red O staining together with the assay of GPDH activity. Assays of cell proliferation and expression of cell cycle-related proteins, along with ROS measurement, qRT-PCR, Western blotting, and immunofluorescence, were performed to evaluate the effects on oxidative stress, transcriptional regulation, and AMPK-Nrf2 signaling. Results: Sesaminol significantly inhibited lipid accumulation and GPDH activity without cytotoxicity. It suppressed MCE by inhibiting DNA synthesis and reducing the expression of cyclin E1/E2 and CDK2. Sesaminol decreased C/EBPβ expression and its nuclear localization, resulting in lower levels of C/EBPα and PPARγ. It also reduced intracellular ROS, promoted nuclear translocation of Nrf2, and upregulated antioxidant genes HO-1 and GCLC. AMPK phosphorylation was concurrently enhanced. Conclusions: Sesaminol inhibits early adipogenesis by suppressing ROS-mediated MCE and activating the AMPK-Nrf2-ARE signaling pathway, leading to downregulation of key adipogenic transcription factors. The present study supports the potential of sesaminol as an effective strategy for obesity prevention. Full article

Background and Objectives: Berberine is a promising phytochemical for obesity prevention due to its effects on adipogenesis and adipose tissue browning. Despite the benefits shown in cell studies, the clinical use of berberine is limited because of its low stability and bioavailability. Materials and Methods: Our study aimed to investigate the effects of intravenous liposomal and free berberine on body weight and adipose tissue browning in C57BL/6J mice. The mice were divided into two main groups for obesity prevention and treatment: the prevention group received treatment with a high-fat diet for 10 weeks; the recovery group received treatment after 10 weeks on a high-fat diet. Treatments included liposomal berberine (10 mcM), free berberine (10 mcM), and void nano-encapsule, and PBS was used as a control. Results: Berberine did not affect body weight in the prevention group. In the treatment group, nano-berberine reduced weight gain, while free berberine caused weight loss (p < 0.05). PRDM16 and CIDEA expressions in white and brown adipose tissues were higher in the berberine-treated groups (p < 0.05). No changes were observed in UCP1, PGC1α, C/EBPβ, and FABP4 expressions. The protein concentrations of UCP1, PGC1α, and PPARγ did not change. Conclusions: The effects of liposomal berberine on gene expression and protein concentrations were not different from the free form, but the nano form had higher stability. Full article

Brassinin, a sulfur-containing phytoalexin, exerts anticancer and anti-inflammatory effects. Hydrogen sulfide (H₂S) is an important gasotransmitter with significant cardioprotective properties. The effects of brassinin on H₂S signaling and vascular smooth muscle cell (SMC) functions remain unexplored. This study found that brassinin protected against angiotensin II (Ang II)-induced SMC dysfunctions. These effects included the attenuation of excessive cell proliferation, migration, and oxidative stress; and upregulation of smooth muscle contractile protein expressions; and down-regulation of inflammatory gene expressions. Notably, brassinin did not directly release H₂S under the tested conditions; instead, it stimulated endogenous H₂S synthesis in cultured SMCs by inducing the expression of cystathionine gamma-lyase (CSE), a key H₂S-generating enzyme. Further mechanistic investigations revealed that brassinin may bind to the transcription factor C/EBPβ and enhance its interaction with the CSE promoter, thereby upregulating CSE transcription. In conclusion, our findings demonstrate that brassinin protects against SMC dysfunction, at least in part, by activating H₂S signaling rather than acting as a direct H₂S donor. These results provide new insights into the potential of brassinin as a therapeutic agent for improving vascular health and preventing cardiovascular diseases. Full article

Stressor stimuli induce oxidative stress and functional abnormalities in sperm, which are linked to a reduced sperm quality and male infertility. Furthermore, oxidative stress can trigger cell death. However, the impact of stressor stimulation on testicles and epididymal sperms and apoptosis has not been explored. This study analyzes the expression of extrinsic and intrinsic apoptotic markers in the testicle and epididymis of rats exposed to chronic variable stress (CVS). We used male Wistar rats divided into two groups: the control group was kept undisrupted, and the stress group was stressed daily using a CVS model for four weeks, except for the weekends (from postnatal days 51 to 81). After the last week, the rats were sacrificed, and complete testicles and epididymal sperm were used to measure oxidative stress and the total antioxidant status by colorimetric methods. The expressions of PPAR-γ, p53, Bax, and Bcl-2 markers at the mRNA level were determined by real-time PCR, and the p-Akt, AP-2α, PPAR-γ, C/EBP-β and FAS protein levels were detected by immunoblot. The results showed low levels of p-Akt and AP-2α proteins and high levels of FAS, PPAR-γ, and C/EBP-β in the testicle and epididymis of rats exposed to CVS. At the mRNA level, we observed the upregulation of PPAR-γ, p53, p21, HIF-α, and Bax expressions in the epididymis of rats exposed to CVS, consistent with the significant caspase-3 activity observed in both the epididymis and testicles in the CVS group. In conclusion, CVS damage triggers the induction of apoptosis markers by intrinsic (PPAR-γ, p53, p21, HIF-α, and Bax) and extrinsic (p-Akt, AP-2α, and FAS) caspase-3-dependent pathways in complete extracts of both the testicles and epididymis. This study supports the view that stressor stimuli could be involved in the infertility process. Full article

Background: The epigenetic regulation of adipogenic differentiation in dental stem cells (DSCs) remains poorly understood, as research has prioritized osteogenic differentiation for dental applications. However, elucidating these mechanisms could enable novel regenerative strategies for soft tissue engineering. Periodontal ligament stem cells (PDLSCs) exhibit notable adipogenic potential, possibly linked to histone 3 acetylation at lysine 9 (H3K9ac); however, the mechanistic role of this modification remains unclear. Methods: To address this gap, we investigated how histone deacetylase inhibitors (HDACis)—valproic acid (VPA, 8 mM) and trichostatin A (TSA, 100 nM)—modulate H3K9ac dynamics, adipogenic gene expression (C/EBPβ and PPARγ-2), and chromatin remodeling during PDLSCs differentiation. Techniques used included quantitative PCR (qPCR), lipid droplet analysis, and chromatin immunoprecipitation followed by qPCR (ChIP-qPCR). Results: TSA-treated cells exhibited increased lipid deposition with smaller lipid droplets compared to VPA-treated cells. Global H3K9ac levels correlated positively with adipogenic progression. VPA induced early upregulation of C/EBPβ and PPARγ-2 (day 7), whereas TSA triggered a delayed but stronger PPARγ-2 expression. ChIP-qPCR analysis revealed significant H3K9ac enrichment at the PPARγ-2 promoter in TSA-treated cells, indicating enhanced chromatin accessibility. Conclusions: These findings demonstrate that H3K9ac-mediated epigenetic remodeling plays a critical role in the adipogenic differentiation of PDLSCs and identifies TSA as a potential tool for modulating this process. Full article

Cellular senescence regulates aging, tissue maintenance, and disease progression through the Senescence-Associated Secretory Phenotype (SASP), a secretory profile of cytokines, chemokines, growth factors, and matrix-remodeling enzymes. While transient SASP aids wound healing, its chronic activation drives inflammation, fibrosis, and tumorigenesis. This review examines SASP’s molecular regulation, dual roles in health and pathology, and therapeutic potential. The following two main strategies are explored: senescence clearance, which eliminates SASP-producing cells, and SASP modulation, which refines secretion to suppress inflammation while maintaining regenerative effects. Key pathways, including NF-κB, C/EBPβ, and cGAS-STING, are discussed alongside pharmacological, immunotherapeutic, gene-editing, and epigenetic interventions. SASP heterogeneity necessitates tissue-specific biomarkers for personalized therapies. Challenges include immune interactions, long-term safety, and ethical considerations. SASP modulation emerges as a promising strategy for aging, oncology, and tissue repair, with future advancements relying on multi-omics and AI-driven insights to optimize clinical outcomes. Full article

Integrin-linked kinase (ILK) is a key scaffolding protein between extracellular matrix protein and the cytoskeleton and has been implicated previously in the pathogenesis of renal damage. However, its involvement in renal mitochondrial dysfunction remains to be elucidated. We studied the role of ILK and its downstream regulations in renal damage and mitochondria function both in vivo and vitro, using a folic acid (FA)-induced kidney disease model. Wild type (WT) and ILK conditional-knockdown (cKD-ILK) mice were injected with a single intraperitoneal dose of FA and studied after 15 days of chronic renal damage progression. Human Kidney tubular epithelial cells (HK2) were transfected with specific siRNAs targeting ILK, glycogen synthase kinase 3-β (GSK3β), or CCAAT/enhancer binding protein-β (C/EBPβ). The expressions and activities of renal ILK, GSK3β, C/EBPβ, mitochondrial oxidative phosphorylation enzymes, and mitochondrial membrane potential were assessed. Additionally, the expression of markers for fibrosis fibronectin (FN) and collagen 1 (COL1A1), for autophagy p62 and cytosolic light chain 3 (LC3B) isoforms II and I, and mitochondrial homeostasis marker carnitine palmitoyl-transferase 1A (CPT1A) were evaluated using immunoblotting, RT-qPCR, immunofluorescence, or colorimetric assays. FA upregulated ILK expression, leading to the decrease of GSK3β activity, increased tubular fibrosis, and produced mitochondrial dysfunction, both in vivo and vitro. These alterations were fully or partially reversed upon ILK depletion, mitigating FA-induced renal damage. The signaling axis composed by ILK, GSK3β, and C/EBPβ regulated CPT1A transcription as the limiting factor in the FA-based impaired mitochondrial activity. We highlight ILK as a potential therapeutical target for preserving mitochondrial function in kidney injury. 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

Background/Objectives: Lagopsis supina, a traditional Chinese medicine valued for its diuretic properties, has limited research on its antioxidant, adipogenic, and anti-inflammatory effects. This study aimed to investigate the chemical composition and biological activities of Lagopsis supina extract (LSE). Methods: LSE was prepared and evaluated for antioxidant activity, effects on adipocyte differentiation in 3T3-L1 preadipocytes, and anti-inflammatory properties in RAW 264.7 macrophages. Ultra-high-performance liquid chromatography-electrospray ionization Orbitrap tandem mass spectrometry (UHPLC-ESI-Orbitrap-MS/MS)-based molecular networking was used to characterize its secondary metabolites. Results: LSE exhibited antioxidant activity in DPPH and ABTS assays. It significantly enhanced the differentiation of 3T3-L1 preadipocytes into mature adipocytes during early and intermediate stages by upregulating adipogenic transcription factors such as PPARγ, C/EBPα, and C/EBPβ, along with promoting cyclin E expression. LSE also increased PPARγ activity and the expression of its target genes, such as Glut 4, PEPCK, FABP4, and Plin2. Moreover, LSE inhibited lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophages by downregulating pro-inflammatory mediators (iNOS, COX-2, TNF-α, IL-6) and inhibiting extracellular signal-regulated kinase (ERK) phosphorylation. Chemical profiling revealed eight major compound groups: glycosides, organic acids, terpenoids, flavonoids, phenylglycosides, phenolics, fatty acids, and others characterized by their mass fragmentation patterns, precursors, and UV absorption spectra. In silico analysis confirmed these compounds’ bioactivities, demonstrating strong interactions and binding affinities with antioxidant, adipogenic, and anti-inflammatory protein targets. Conclusions: These findings highlight LSE’s triple therapeutic potential: antioxidant activity, adipogenesis promotion, and inflammation attenuation. LSE emerges as a promising therapeutic candidate for managing obesity and related inflammatory complications. Full article

GATA-3 is a master regulator of preadipocyte differentiation and function. Pharmacological or genetic targeting of GATA-3 will allow us to understand the function of GATA-3 in regulating metabolism, insulin signaling, and inflammation. Pyrrothiogatain, a novel small molecule inhibitor of GATA family proteins, has emerged as a promising tool for modulating GATA-3 activity. This study aims to investigate the specificity of Pyrrothiogatain in regulating GATA-3-mediated preadipocyte differentiation and adipokine secretion under normal and pathological conditions. Wild-type and GATA-3 knockout 3T3-L1 cells were treated with different concentrations of Pyrrothiogatain in the presence and absence of 4-hydroxy-2-nonenal (4HNE), an inducer of oxidative stress and impairment of adipogenesis. As expected, GATA-3 knockout cells exhibited enhanced adipogenic capacity, characterized by increased cell and lipid droplet sizes, and upregulated expression of key adipogenic markers including CEBPβ, PPARγ, and PGC-1α. Pyrrothiogatain treatment reduced cell proliferation in both wild-type and GATA-3 knockout 3T3-L1 cells, but did not alter their adipogenic capacity. Furthermore, Pyrrothiogatain lowered secreted IL-6 levels and attenuated 4-HNE-induced TNF-α elevation in wild-type, but not in GATA-3 knockout cells. Co-treatment of 4-HNE and Pyrrothiogatain led to increased cell size, suggesting complex interactions between oxidative stress and GATA protein inhibition. This effect was similar to GATA-3 knockout cells, indicating Pyrrothiogatain’s potential to modulate cellular stress responses independently of GATA-3 inhibition. These results reveal that Pyrrothiogatain’s effects on adipocyte biology extend beyond simple GATA-3 inhibition. While GATA-3 knockout primarily affects adipogenesis, Pyrrothiogatain modulates inflammatory responses and potentially cellular stress mechanisms without directly impacting adipocyte differentiation. This study provides new insights into the multifaceted actions of Pyrrothiogatain and highlights its potential as a therapeutic agent for lowering inflammation and oxidative-stress-related aspects of metabolic disorders, distinct from the direct modulation of adipogenesis. Full article