Curcumin alleviates hepatic steatosis by improving mitochondrial function in postnatal overfed rats and fatty L02 cells through the SIRT3 pathway

Abstract

Postnatal overfeeding damaged mitochondrial biogenesis and antioxidant response, and increased hepatic lipids and the severity of high-fat-induced NAFLD, while curcumin alleviated hepatic steatosis, at least partially, by enhancing mitochondrial function through SIRT3.

Abstract

Postnatal overfeeding could increase the risk of non-alcoholic fatty liver disease (NAFLD) in adulthood. This study investigated the effects of curcumin (CUR) on hepatic steatosis in postnatal overfed rats and elucidated potential mechanisms in mitochondrial functions. Male rats were adjusted to ten (normal litter, NL) or three (small litter, SL) at postnatal day 3. After weaning, NL rats were fed with normal diet (NL) or a high-fat diet (NH) for 10 weeks. SL rats were fed with normal diet (SL), a high-fat diet (SH), a normal diet supplemented with 2% CUR (SL-CUR) or a high-fat diet supplemented with 2% CUR (SH-CUR). At week 13, compared with NL rats, SL and NH rats showed increased body weight, glucose intolerance, dyslipidemia and hepatic lipid accumulation, and these changes were more obvious in SH rats. The opposite trends were observed in SL-CUR and SH-CUR rats. Moreover, CUR could preserve mitochondrial biogenesis and antioxidant response in postnatal overfed rats, and upregulated the mRNA and protein levels of SIRT3. In vitro, L02 cells were exposed to free fatty acids and/or CUR. CUR decreased the levels of cellular lipids and mitochondrial reactive oxygen species, and increased the mitochondrial DNA copy number and superoxide dismutase activity in fatty L02 cells. However, these effects were blocked after SIRT3 silencing. It was concluded that postnatal overfeeding damaged mitochondrial biogenesis and antioxidant response, and increased hepatic lipids and the severity of high-fat-induced NAFLD, while CUR alleviated hepatic steatosis, at least partially, by enhancing mitochondrial function through SIRT3.