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BackgroundThe prevalence of obesity is increasing worldwide and significantly affects fertility and reproduction in both men and women. Our recent study has shown that excess body fat accelerates ovarian follicle development and follicle loss in rats. The aim of the present study is to explore the effect of SIRT1 activator SRT1720 on the reserve of ovarian follicle pool and ovarian lifespan of obese mice and the underlying mechanism associated with SIRT1 and mTOR signaling.MethodsAdult female Kunming mice (n = 36) were randomly divided into three groups: the normal control (NC) group (n = 8), the caloric restriction (CR) group (fed 70% food of the NC group, n = 8) and the high-fat diet (HF) group (fed a rodent chow containing 20% fat, n = 20). After 4 months, the HF mice were further randomly divided into three groups: the control high-fat diet (CHF, n = 8) group (treated every day with an intraperitoneal injection of vehicle), the SRT1720 (SRT, n = 6) group (treated every other day with an intraperitoneal injection of SRT1720 (50 mg/kg)), the SRT1720 and nicotinamide (NAM, n = 6) group (treated every other day with an intraperitoneal injection of SRT1720 (50 mg/kg) and every day with an intraperitoneal injection of nicotinamide (100 mg/kg)). After 6 weeks of treatment, ovaries were harvested for histological and Western blotting analyses.ResultsThe body weight, ovary weight and visceral fat in the SRT group were significantly lower than those in the CHF group at the end of treatment. Histological analysis showed that the SRT mice had significantly greater number and percentage of primordial follicles, but lower number and percentage of corpora lutea and atretic follicles than the CHF mice and NAM mice. Western blot analysis demonstrated that the levels of SIRT1, SIRT6, FOXO3a and NRF-1 protein expression significantly increased in the ovaries of SRT mice, whereas those of mTORC1, p-mTOR, p-p70S6K, NFκB and p53 decreased compared to the CHF and NAM mice.ConclusionsOur study suggests that SRT1720 may improve the follicle pool reserve in HF diet-induced obese female mice via activating SIRT1 signaling and suppressing mTOR signaling, thus extending the ovarian lifespan.

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BackgroundSilent information regulator 2 related enzyme 1 (SIRT1) is one of the key factors in the mechanism of calorie restriction (CR) extending lifespan of animals. The aim of the study is to investigate if CR prolongs ovarian lifespan in mice through activating SIRT1 signaling.MethodsIn the present study, 21 female C57BL/6 mice were divided into three groups: the control (n = 7), CR (n = 7), and SRT1720 (n = 7) groups. After the 26-week treatment, the number of ovarian follicles at each stage was counted, and Western blot was performed.ResultsThe number of surviving follicles in ovaries of the SRT1720 group was less than that of the CR group but more than that of the normal control (NC) group. The number of atretic follicles in the ovaries of the SRT1720 group was similar to that of the CR group but less than that of the NC group. The number of primordial follicles in the ovaries of the SRT1720 group was less than that of the CR group but more than that of the NC group. The numbers of primary follicles, secondary follicles, antral follicles, and corpora lutea in the SRT1720 group were similar to those in the CR group. Western blot analysis showed that the expression of SIRT1, SIRT6, FOXO3a, and NRF1 proteins was upregulated, and p53 was downregulated in both the CR group and the SRT1720 group compared to the control group.ConclusionsOur results indicate that CR inhibits the activation of primordial follicles and development of follicles at different stages, thus preserving the reserve of follicle pool (at least partly) through activating SIRT1 signaling.