Choi_2023_Int.J.Mol.Med_52_

Obesity is associated with high risk of mortality globally because obesity is associated with development of diseases such as diabetes, dyslipidemia, fatty liver disease, hypertension, and cancer. The present study aimed to identify the mechanism of action related to the anti-obesity activity of Paeonia lactiflora root (PLR) based on its effects on lipid droplet accumulation. The inhibitory activity on lipid accumulation was analyzed through Oil-Red O staining, and the changes in levels of lipid accumulation-related proteins were analyzed using Western blot analysis. And the contents of triacylglycerol and free glycerol were analyzed using an ELISA Kit. PLR significantly inhibited the accumulation of lipid droplets and triacylglycerol in differentiating 3T3-L1 cells. PLR increased phosphorylated-hormone sensitive lipase (HSL), HSL and adipose triglyceride lipase (ATGL) and decreases perilipin-1 in differentiating and fully differentiated 3T3-L1 cells. Furthermore, treatment of fully differentiated 3T3-L1 cells with PLR resulted in increased free glycerol levels. PLR treatment increased levels of peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1alpha), PR domain containing 16 (PRDM16) and uncoupling protein 1 (UCP-1) in both differentiating and fully differentiated 3T3-L1 cells. However, the PLR-mediated increase in lipolytic, such as ATGL and HSL, and thermogenic factors, such as PGC-1a and UCP-1, were decreased by inhibition of AMP-activated protein kinase (AMPK) with Compound C. Taken together, these results suggest that PLR exerted anti-obesity effects by regulating lipolytic and thermogenic factors via AMPK activation. Therefore, the present study provided evidence that PLR is a potential natural agent for the development of drugs to control obesity.