To elucidate the mechanisms underlying the anti-obesity properties of Centella asiatica (CA), this study evaluated body weight, serum profiles, white adipose tissue (WAT) mass, histological characteristics, and the expression of genes associated with cholesterol homeostasis and lipid metabolism. These parameters were assessed in mice with obesity induced by a high-fat, high-sugar diet (HFHSD) following oral administration of CA for 12 weeks. Male C57BL/6J mice, aged eight weeks, were divided into four experimental cohorts (8 mice/group): NOR, normal diet; HFHSD (Control), HFHSD; CA-L, HFHSD + CA 300 mg/kg; and CA-H, HFHSD + CA 600 mg/kg. A suspension of powdered CA leaves was administered via oral gavage. Treatment with CA significantly mitigated the HFHSD-induced elevations in body weight gain, serum glucose, triacylglycerol concentrations, and WAT mass (p < 0.05). In comparison to the HFHSD control group, both the diameter of adipocytes and the macrovesicular area within the epididymal WAT were significantly reduced following CA intervention (p < 0.05). Furthermore, the mRNA expression levels of peroxisome proliferator-activated receptor gamma (PPARγ), fatty acid synthase (FAS), cluster of differentiation 36 (CD36), 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR), and stearoyl CoA desaturase 1 (SCD 1) exhibited significant downregulation in the CA-H group relative to the HFHSD group (p < 0.05). Therefore, CA demonstrates anti-obesity efficacy by suppressing body fat accumulation through the modulation of gene expression, highlighting its potential as a lipid-lowering therapeutic agent.
