Capsaicin ameliorates fatty accumulation both in mouse liver and in human hepatocytes

Abstract

Abstract Background:Nonalcoholic fatty liver disease (NAFLD) is a continuous spectrum of the disease recognized as excessive fatty accumulation in the liver, and no effective drugs are approved by FDA. Present study aimed to investigate whether capsaicin, the major ingredients of pepper, can ameliorate the progression of NAFLD. The underlying mechanism was also explored. Methods:The function of capsaicin on lipid accumulation was assessed both in high-fat high-sugar diet (HFHSD) induced mice and in human hepatocytes. In animal experiments, mice were divided into three groups: normal diet (ND), HFHSD, and HFHSD subjected to capsaicin cream. The body weight, liver weight, lipid droplets, triglyceride (TG), and total cholesterol (TC) of each group were compared. In cell experiments, WRL68 cells were cultured with the palmitic and oleic acid (PAOA) mixture. The lipid accumulation was detected using fluorescence microscopy and flow cytometer. RT-qPCRwas performed to explore the potential mechanism of capsaicin. Results: Topical application of capsaicin significantly decreased liver index (HFHSD vs HFHSD + Cap, 6.92 ± 1.47 vs 6.16 ± 1.13, mean ± SEM, n = 8) and ameliorated hepatic fatty accumulation (HFHSD vs HFHSD + Cap, 22.54 ± 4.53 vs 9.92 ± 4.42, mean ± SEM, n = 8) in HFHSD-fed mice. Capsaicin treatment decreased intracellular lipid accumulation in human hepatocytes. RT-qPCR showed that HFHSD feeding or PAOA exposure could significantly up-regulate the levels of SREBP-1c, ACC1, and CYP2E1, while capsaicin application reversed their expression. Conclusion: Topical application of capsaicin ameliorates fatty accumulation both in mice and human hepatocytes, which may be related to de novo lipogenesis inhibition and ω-oxidation regulation.