Inhibition of uncoupling protein 2 with genipin exacerbates palmitate-induced hepatic steatosis
- Equal contributors
Department of Cardiology, General Hospital of PLA Chengdu Military Area Command, 270 Rongdu Rd., Tianhui Town, Jinniu District, Chengdu, 610083, Sichuan Province, People’s Republic of China
Lipids in Health and Disease 2012, 11:154 doi:10.1186/1476-511X-11-154Published: 14 November 2012
Uncoupling protein 2 (UCP2) was reported to be involved in lipid metabolism through regulating the production of superoxide anion. However, the role of UCP2 in hepatocytes steatosis has not been determined. We hypothesized that UCP2 might regulate hepatic steatosis via suppressing oxidative stress.
We tested this hypothesis in an in vitro model of hepatocytic steatosis in HepG2 cell lines induced by palmitic acid (PA). We found that treatment with PA induced an obvious lipid accumulation in HepG2 cells and a significant increase in intracellular triglyceride content. Moreover, the specific inhibition of UCP2 by genipin remarkably exacerbated PA-induced hepatocytes steatosis. Interestingly, the PA-induced superoxide overproduction can also be enhanced by incubation with genipin. In addition, administration with the antioxidant tempol abolished genipin-induced increase in intracellular lipid deposition. We further found that genipin significantly increased the protein expression of fatty acid translocase (FAT)/CD36.
These findings suggest that UCP2 plays a protective role in PA-induced hepatocytic steatosis through ameliorating oxidative stress.