LONG-TERM CALORIC RESTRICTION IMPROVES MYOCARDIAL SIRT1/AMPK/PGC-1A PATHWAY IN C57BL/6J MICE

Abstract

Objective: Caloric restriction (CR) is capable of improving heart function, there is as yet no consensus on the mechanism of effect of CR. Silent mating-type information regulation 1 (SIRT1), adenosine monophosphate-activated protein kinase (AMPK), and mTOR are key players in metabolic stress management. We aimed to explore the effect of CR on myocardial SIRT1/AMPK/mTOR pathway in mice. Design and method: Thirty 6-week-old male C57BL/6J mice were randomly divided into three groups: normal control group (NC group, n = 12), high-energy group (HE group, n = 12) and CR group (n = 12) according to different diet. After 11 months, western blot was used to examine proteins such as p-AMPK, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1a), SIRT1, and p-mTOR, whereas real-time PCR was used to examine the expression of AMPK, PGC-1a, and SIRT1 transcripts. Results: Compared with NC group, the CR group displayed increased expression of myocardial p-AMPK, SIRT1 protein and mRNA, and PGC-1a mRNA. However, no difference was observed in the expression of p-mTOR protein and mTOR mRNA in the myocardium among the three groups. Conclusions: CR improves SIRT1/AMPK/PGC-1a pathway in mice myocardium with no effect on the mTOR pathway.