<i>Angelica gigas</i> Nakai extract exerts anti-obesity effects by inducing lipolysis and thermogenesis in 3T3-L1 adipocytes

Angelica gigas Nakai (AGN) is a widely utilized herbal remedy in traditional oriental medicine, recognized for its anticancer, anti-oxidant, and immune-enhancing effects.Previous studies have AGN's anti-obesity effects, suppressing adipocyte differentiation and alleviating hepatic steatosis and dyslipidemia.However, the effects of AGN on lipolysis and thermogenesis in adipocytes have not yet been reported.In this study, we confirmed AGN's ability to induce lipolysis through the protein kinase A (PKA)-mediated activation of hormone sensitive lipase (HSL) in 3T3-L1 adipocytes and to promote uncoupling protein 1 (UCP1)dependent thermogenesis by utilizing free fatty acid (FFA) as substrates.AGN significantly reduced lipid accumulation in 3T3-L1 adipocytes while simultaneously increasing the release of glycerol and FFAs.Furthermore, AGN increased the phosphorylation of PKA-specific HSL residues (ser563 and ser660) and perilipin at the protein level.Pre-treatment with the PKA inhibitor, H89, reduced this phosphorylation, confirming its role in AGN-induced lipolysis.In addition, AGN increased intracellular FFA availability by activating peroxisome proliferator-activated receptor alpha and modulating the primary components of thermogenic functions, including UCP1.Collectively, this study is the first to demonstrate AGN's ability to enhance lipolysis and thermogenesis, a previously unreported mechanism for triglyceride metabolism.