Metformin attenuates lipid accumulation in hepatocytes of blunt snout bream (Megalobrama amblycephala) via activation of AMP-activated protein kinase

Abstract

Currently, there is a trend to use high-fat diets in intensive aquaculture that is accompanied with incidence of fatty liver when dietary lipid level surpasses an upper limit. So, it is necessary to develop appropriate strategies to reduce the risk of fatty liver in commercial fish farming. Studies in mammals have revealed a correlation between fatty liver and AMP-activated protein kinase (AMPK) activity, which has been recognized as a key modulator of lipid metabolism. Considering the frequent occurrence of fatty liver in blunt snout bream farming, an in-vitro study was designed to evaluate the efficiency of metformin, as a stimulator of AMPK, in activation of AMPK and its subsequent effects on lipid metabolism in primary hepatocytes. Fish hepatocytes were seeded at a density of 1 × 106 ml−1 in 6-well tissue culture plates and treated with three different media including: 1) Leibovitz's L-15 medium [L15] as control, 2) high-fat medium [L15 + 400 μM oleic acid], and 3) metformin medium [L15 + 400 μM oleic acid+200 μM metformin]. After 48 h of culture, the cells and supernatant were collected for analysis. The results showed significant (P