Related Experiment Video
Updated: Dec 28, 2025
Investigation of Beige Fat Biology and Metabolism Using the CRISPR SunTag-p65-HSF1 Activation System
Published on: January 6, 2023
Long-term caloric restriction activates the myocardial SIRT1/AMPK/PGC-1α pathway in C57BL/6J male mice
Lina Ma1,2, Rong Wang2, Hongjuan Wang3
1Department of Geriatrics, Xuanwu Hospital Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, China.
Background:
Caloric restriction (CR) can help in improving heart function. There is as yet no consensus on the mechanism of the 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 the myocardial SIRT1/AMPK/mTOR pathway in mice.
Methods:
Thirty-six 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 diets. After 11 months, western blot was used to examine proteins such as p-AMPK, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), SIRT1, and p-mTOR, whereas real-time PCR was used to examine the expression of AMPK, PGC-1α, and SIRT1 transcripts.
Results:
Compared to the HE group, the CR group displayed increased expression of myocardial p-AMPK protein, 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 the SIRT1/AMPK/PGC-1α pathway in mice myocardium with no effect on the mTOR pathway.
Insights
Caloric restriction (CR) enhances heart function by activating the SIRT1/AMPK/PGC-1α pathway in mice. This study clarifies the molecular mechanisms underlying CR
Area of Science:
- Cardiovascular Research
- Metabolic Regulation
- Molecular Biology
Background:
- Caloric restriction (CR) is known to improve cardiac function, but the underlying mechanisms remain unclear.
- Key metabolic regulators, including Silent mating-type information regulation 1 (SIRT1), adenosine monophosphate-activated protein kinase (AMPK), and mTOR, are implicated in stress response.
- Understanding these pathways is crucial for developing strategies to enhance cardiovascular health.
Purpose of the Study:
- To investigate the impact of caloric restriction (CR) on the SIRT1/AMPK/mTOR signaling pathway within the myocardium.
- To elucidate the molecular mechanisms by which CR influences cardiac function.
- To determine the role of SIRT1, AMPK, and mTOR in mediating the cardioprotective effects of CR.
Main Methods:
- Thirty-six male C57BL/6J mice were allocated into three dietary groups: normal control (NC), high-energy (HE), and caloric restriction (CR).
- Mice were maintained on their respective diets for 11 months.
- Western blot and real-time PCR were employed to quantify the expression of key proteins and transcripts, including p-AMPK, PGC-1α, SIRT1, and p-mTOR.
Main Results:
- Caloric restriction significantly increased the expression of myocardial p-AMPK protein, SIRT1 protein, and SIRT1 mRNA compared to the high-energy group.
- The expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) mRNA was also elevated in the CR group.
- No significant differences in the expression of p-mTOR protein or mTOR mRNA were observed among the three groups.
Conclusions:
- Caloric restriction positively modulates the SIRT1/AMPK/PGC-1α pathway in the mouse myocardium.
- The mTOR pathway was not affected by caloric restriction in this study.
- These findings provide mechanistic insights into how CR improves cardiac health, highlighting the SIRT1/AMPK/PGC-1α axis.
