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To understand the mechanisms involved in the anti-obesity effects Centella asiatica (CA), we examined body weight, serum levels, white adipose tissue (WAT) weight, histological analysis, and the expression of cholesterol homeostasis- and lipid metabolism-related genes in mice with high-fat, high-sugar diet (HFHSD)-induced obesity that were orally treated with CA for 12 weeks. Eight-week-old, male C57BL/6J mice were assigned to the following four groups (8 mice/group): NOR, normal diet; HFHSD (Control), HFHSD; CA-L, HFHSD + CA 300 mg/kg; CA-H, HFHSD+CA 600 mg/kg. The suspension of powdered CA leaf was fed using oral gavage. CA treatment significantly attenuated HFHSD-induced increase in body weight gain, serum glucose, triacylglycerol, and WAT weight (p < 0.05). Compared to that in HFHSD, adipocyte diameter and macrovesicular area of epididymal WAT significantly decreased with CA treatment (p < 0.05). The mRNA expression levels of peroxisome proliferator-activated receptor gamma (PPARγ), fatty acid synthase (FAS), cluster of differentiation 36 (CD36), 3- hydroxyl-3-methylglutaryl CoA reductase (HMGCR), and stearoyl CoA desaturase 1 (SCD 1) were significantly downregulated in the CA-H compared to the HFHSD (p < 0.05). CA exerts anti-obesity effects by lowering body fat accumulation via regulating gene expression and thus, is a potential lipid-lowering agent.

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.