Trehalose-induced SIRT1/AMPK activation regulates SREBP-1c/PPAR-α to alleviate lipid accumulation in aged liver.

Aging is associated with a disturbance in the regulation of the metabolic function of the liver, which increases the risk of liver and systemic diseases. Trehalose, a natural disaccharide, has been identified to reduce dyslipidemia, hepatic steatosis, and glucose intolerance. However, the roles of trehalose on lipid metabolism in aged liver are unclear which was investigated in this study. Thirty-two male Wistar rats were randomly allocated into four groups (n = 8). Two groups of aged (24 months) and young (4 months) rats were administered 2% trehalose solution orally for 30 days. Control groups of aged and young rats did not receive any treatment. At the end of the treatment period, blood samples and liver tissues were collected. Then the expression of SIRT1, AMPK, SREBP-1c, and PPAR-α and the level of AMPK phosphorylation (p-AMPK) were quantified by real-time polymerase chain reaction and western blotting. Moreover, biochemical parameters and the histopathology of livers were evaluated. Trehalose supplementation increased the level of SIRT1, p-AMPK, and PPAR-α, whereas the level of SREBP-1c was diminished in the liver of old animals. In addition, treatment with trehalose improved histopathological features of senescent livers. Taken together, our results show that old rats developed lipogenesis in the liver which was alleviated with trehalose. Therefore, trehalose may be an effective intervention to reduce the progression of aging-induced liver diseases.