Coptisine inhibits lipid accumulation in high glucose- and palmitic acid-induced HK-2 cells by regulating the AMPK/ACC/CPT-1 signaling pathway.

AMPK (Adenosine 5'-Monophosphate activated Protein Kinase) functions as a fundamental regulator of glycolipid metabolism by regulating the rate-limiting enzyme activity of ACC (Acetyl-CoA Carboxylase, essential for fatty acid biosynthesis) and CPT-1 (Carnitine palmitoyltransferase-1, essential for mitochondrial fatty acid oxidation, FAO) in cells, which is crucial for maintaining energy homeostasis in the human body. Coptisine (COP) is a natural berberine and isoquinoline alkaloid in Coptis chinensis that has been used as a traditional Chinese herb to treat diabetes for thousands of years, but its mechanism of action is still unclear. In this study, we investigated the anti-lipid accumulation effect and mechanism of COP in high glucose and palmitic acid-induced HK-2 cells. Compared with the control HK-2 cells, the model HK-2 cells exhibited markedly greater lipid deposition, after treatment with high glucose (HG, 30 mM) and palmitic acid (PA, 250 µM) for 24 h. However, COP significantly decreased the TC and TG levels in a dose dependent manner (2.5, 5, and 10 µM). Moreover, COP dramatically enhanced the effect of the positive control (AICAR, Acadesine, an AMPK activator) in alleviating lipid deposition, which was reversed by the negative control (Compound C, an AMPK inhibitor). Furthermore, COP also increased p-AMPK, p-ACC and CPT-1 protein expression. Our results indicate that COP can effectively protects HK-2 cells against HG- and PA-induced lipid accumulation by affecting the AMPK/ACC/CPT-1 signaling pathway, inhibiting de novo lipogenesis and enhancing the FAO processes, which offers novel insights for the application of COP in the clinic.