What's the role of SIRT1-dependent mechanism in the progress of gluconeogenesis and lipogenesis?

Caton PW, Nayuni NK, Khan NQ, Wood EG, Corder R "JOURNAL OF ENDOCRINOLOGY MAR 2011"

Consumption of the fructose-rich diet results in insulin resistance and dyslipidemia in part because of elevated gluconeogenesis and lipogenesis. SIRT1, an NAD(+)-dependent protein deacetylase, can induce gluconeogenesis and lipogenesis.

The aim of this research was to decide whether fructose increased hepatic SIRT1, top to induction of gluconeogenesis and lipogenesis. Rat hepatocytes were incubated with fructose (1-5 mM). SIRT1 protein, SIRT1 exercise, and NAD(+)/NADH ratio had been measured.

The consequences of SIRT1 inhibitors (EX-527 and nicotinamide) and activators (SIRT1 activator three and SRT1720) as well as the mitochondrial complicated I inhibitor rotenone were examined on fructose-induced raises in gluconeogenesis and lipogenesis. Fructose increased SIRT1 protein, SIRT1 exercise, and NAD(+)/NADH ratio. Fructose also induced gluconeogenesis, with increases in peroxisome proliferator-activated receptor coactivator 1-alpha (PGC1 alpha) and phosphoenolpyruvate carboxykinase (PEPCK, gene code Pck1) gene expression, PEPCK exercise, and hepatocyte glucose production.

In addition, ranges of 3-hydroxy-3-methylglutaryl coenzyme A reductase (Hmgcr) and acetyl-coA carboxylase (Acc) mRNA, and intracellular cholesterol were increased. Raises in gluconeogenesis, Hmgcr, Acc, and cholesterol had been abolished by SIRT1 inhibitors and rotenone, while SIRT1 activators increased gluconeogenesis, Hmgcr, Acc, Pgc1 beta, and sterol regulatory element-binding protein 1c (Srebp1c) gene expression.

In summary, fructose induces gluconeogenesis and lipogenesis by means of a SIRT1-dependent mechanism, suggesting that induction of hepatic SIRT1 could play a pivotal part in the metabolic changes observed in people and animals consuming a fructose-rich diet. These outcomes highlight the want for any higher knowing in the function of SIRT1 in metabolic regulation and show the possible for undesirable consequences of SIRT1 activators if employed therapeutically.