Moderate calorie restriction ameliorates reproduction via attenuating oxidative stress-induced apoptosis through SIRT1 signaling in obese mice

Shaohong Zhang; Mengxiao Zhang; Shuoshuo Sun; Xiao Wei; Yu Chen; Peng Zhou; Rendong Zheng; Guofang Chen; Chao Liu

doi:10.21037/atm-21-2458

Moderate calorie restriction ameliorates reproduction via attenuating oxidative stress-induced apoptosis through SIRT1 signaling in obese mice

Ann Transl Med. 2021 Jun;9(11):933. doi: 10.21037/atm-21-2458.

Authors

Shaohong Zhang^{1

2}, Mengxiao Zhang^{1

2}, Shuoshuo Sun^{1

2}, Xiao Wei^{1

2}, Yu Chen^{1

2}, Peng Zhou^{1

2}, Rendong Zheng^{1

2}, Guofang Chen^{1

2}, Chao Liu^{1

2}

Affiliations

¹ Endocrinology Department, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
² Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, China.

Abstract

Background: Obesity is a growing global public health problem. It has been associated with diabetes, cardiovascular disease, cancer, and an increased risk of all-cause mortality, as well as infertility. Calorie restriction (CR) is an effective life intervention to defend against obesity. This study aimed to investigate the effects of long-term moderate CR on the reproductive function and underlying mechanisms in a mouse model of obesity.

Methods: Male C57BL/6 mice were randomized to two groups receiving either a standard diet (STD) or a high-fat diet (HFD) for 8 weeks to induce obesity. The HFD-induced obesity mice were further randomized into two groups: HFD group and CR group (reduced the mean amount of HFD by 25%). After 12 weeks, the body weight, testicular coefficients, fasting blood glucose (FBG), serum triglyceride (TG), and total cholesterol (TC) were detected and measured. The sperm quality was detected by an automatic sperm quality analyzer (SQA-V). The structure of testicular tissues was examined by hematoxylin and eosin (HE) staining. Testicular cell apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. The levels of NAD-dependent deacetylase sirtuin-1 (SIRT1) and antioxidative enzymes were detected in the testes.

Results: CR treatment reduced weight gain and increased testicle coefficients in HFD-induced obese mice. CR reduced the serum level of FBG, TG, and TC, and increased the serum levels of testosterone. Moreover, CR increased sperm count and motility, and sperm normality in obese mice. Furthermore, CR ameliorated the testicular morphological damage and cell apoptosis in obese mice. CR also attenuated the oxidative stress level and increased the protein expressions of SIRT1 in testicular tissues of obese mice.

Conclusions: Long-term moderate CR improves obese male fertility, probably by alleviating oxidative stress via activation of SIRT1 signaling.

Keywords: Calorie restriction (CR); apoptosis; high-fat diet (HFD); oxidative stress; reproduction.