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

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.

A short-term high-fat diet alters rat testicular activity and blood-testis barrier integrity through the SIRT1/NRF2/MAPKs signaling pathways

“…Third, SIRT1 regulates mitochondrial function and energetic metabolism activating PGC-1a through deacetylation and mediating the induction of several components of the ROS detoxifying system (93). Fourth, testicular SIRT1 downregulation has previously been associated with the insurgence of an oxidative stress status (94) and in HFD-fed mice (53,95). In view of these considerations, supporting earlier reports, we hypothesize that the effect of a st-HFD on impaired spermatogenesis may be also due to the downregulation of SIRT1 expression/activity and, consequently, of the downstream pathways, including those regulating mitochondrial dynamics.…”

Oxidative Stress and Male Infertility: Evidence From a Research Perspective

“…Several other studies, both animal and human have highlighted that in obesity, there is excessive production of ROS, leading to OS and consequently induce apoptosis, which may further lead to reduced reproductive potential or subfertility (139)(140)(141)(142)(143). Some showed the disruption of the blood-testis barrier (141) in obesity, while some suggested that the duration have an unfavorable impact on male fertility (142,143).…”

Preconceptional paternal caloric restriction of high-fat diet-induced obesity in Wistar rats dysregulates the metabolism of their offspring via AMPK/SIRT1 pathway

“…Consequently, this undernourished condition had adverse repercussions on male fertility and impacted the health of their offspring. Whereas, A study has found that moderate CR of obese male mice leads to the upregulation of SIRT1 which has beneficial effects on reproductive health [48]. In line, another study also demonstrated that SIRT1 knock-out mice has resulted in altered number & morphology of spermatozoa, causing reduced fertility [49].…”