Sestrins' Expression in the Liver Is Not Altered by Short-Term Calorie Restriction in Young and Old Rats

Abstract

Introduction: Short-term calorie restriction (SCR) may have a positive impact on health. We hypothesized that sestrins, a family of stress-inducible proteins (Sesn1, Sesn2, Sesn3) are involved in the response to SCR in the liver.

Methods: Young-adult (4-month) and old (24-month) male Wistar rats were either fed ad libitum (control groups) or received 60% of food intake on a daily basis for 30 days (SCR groups). In blood sera, biochemical parameters and fibroblast growth factor 21 (FGF21) concentration were measured (ELISA). Liver samples were collected for analyses of genes' expression (real-time PCR) and protein levels (Western blotting).

Results: SCR caused improvements in blood glucose and lipids and parameters of liver function but did not affect the serum FGF21 concentration. SCR caused changes typically associated with calorie restriction in the gene expression of fatty acid synthase (fasn), ATP-citrate lyase (acly), and sirtuin 1 (sirt1). In the liver of young SCR rats, protein level of Sesn2 tended to increase, while Sesn3 tended to decrease, accompanied by reduced sesn3 expression. In old SCR rats, reduced sesn1 expression was reflected by decreasing trend for Sesn1 content. Activation of AMP-activated protein kinase (phospho-Thr172) and protein content of peroxisome proliferator-activated receptor gamma coactivator 1-alpha were not affected by SCR.

Conclusion: Sestrins' hepatic expression is only minimally affected by SCR in young and old rats. We propose that sestrins may not be a major effector of mild SCR in the liver of young or old rats.

Keywords: Aging; Liver; Rat; Sestrin; Short-term calorie restriction.

Fig. 1

Body mass (a) and the mass of total sampled WAT (b) of control (C) and treated rats after 30-day CR. Data present mean ± SD of 8–10 animals per group. *p < 0.05, ***p < 0.001.

Fig. 2

FGF21 level in blood serum of control (C) and short-term calorie-restricted (SCR) rats, mean ± SD, n = 8–10 animals per group, no significant differences.

Fig. 3

Hepatic mRNA expression of genes commonly affected by CR. The mRNA levels of fasn, acly, and sirt1 were normalized to young C. Data are means ± SD, n = 8–10 animals per group. yC, young control; ySCR, young short-term calorie-restricted rats; oC, old control; oSCR, old short-term calorie-restricted rats; **p < 0.01, ***p < 0.001.

Fig. 4

Hepatic mRNA expression of sestrins in control (C) and short-term calorie-restricted rats (SCR), normalized to young C. Data are means ± SD, n = 8–10 animals per group. **p < 0.01, ***p < 0.001.

Fig. 5

Protein levels of sestrins, pAMPK/AMPK, and Pgc1α in young (y) or old (o) C and calorie-restricted rats. Representative blots are shown (a), as well as graphs of the protein levels (b) normalized to young C rats; data are means ± SD of n = 4–6 animals per group, *p < 0.05.