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Context: Obesity is gradually becoming a widespread health problem, and treatment using natural compounds has seen an increasing trend. The aim of this study investigated the effects and underlying mechanisms of Cissus quadrangularis (Cissuslean®) on adipogenesis and high-fat diet (HFD)-induced obesity. The inhibitory effects of Cissuslean® on adipocyte differentiation were evaluated in vitro using 3T3-L1 preadipocyte cells, focusing on AMPK signaling and lipid metabolism. Subsequently, an in vivo trial with male C57BL/6J mice fed HFD was conducted to examine the effects of Cissuslean® at 25, 50, and 100 mg/kg on adipose tissue characteristics, body weight, fat mass, and obesity-related gene expression. Cissuslean® significantly inhibited preadipocyte differentiation by reducing intracellular lipid accumulation and suppressing the expression of key adipogenic regulators. It also enhanced AMPK phosphorylation during early adipocyte differentiation. In HFD-induced obese mice, Cissuslean® administration resulted in marked reductions in body weight gain, adipose tissue mass, and hepatic lipid accumulation. Furthermore, decreased serum ALT and AST levels indicated attenuation of HFD-induced hepatic injury. According to these results, Cissuslean® reduces body fat mass by inhibiting lipase activity and regulating genes and proteins involved in adipogenesis and lipogenesis in epididymal adipose tissue. Our results suggest that Cissuslean® may be used as an anti-obesity agent.
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