Protective Effects of Fluvastatin on Reproductive Function in Obese Male Rats Induced by High-Fat Diet through Enhanced Signaling of mTOR

Abstract

Background: Statins can reduce reproductive damage induced by obesity or high-fat diet (HFD), but the specific regulatory mechanisms are largely unknown. Since mTOR/p70s6k sinaling promotes spermatogonia proliferation and spermatogenesis, we hypothesized that this pathway will be involved in the protective effects of statin in HFD-induced reproductive dysfunction. Methods: Male Sprague Dawley rats (3 weeks old) were randomly divided into a control group (standard diet), HFD group, and a fluvastatin group (HFD + fluvastatin at 6mg/kg, once daily by oral gavage). After 8 weeks, body weight was obtain and rats were sacrificed. Weights of the testes, gross morphology, sperm parameters, circulating levels of sex hormones, lipid levels, and tissue mTOR, p-P70s6k were measured. Another set of male rats were treated with rapamycin or vehicle. Flow cytometry was used to detect the spermatogonia marker c-kit and cell cycle. p-P70s6k expression was analyzed by Western blot. Results: HFD not only results in rat obesity but also leads to spermatogenetic damage and fluvastatin was able to partially block the effects of HFD. Fluvastatin also partially reversed the suppression of mTOR and p-p70s6k expresson. Conclusion: Our data suggest that fluvastatin has protective effects on reproductive function in obese male rats most probably through enhanced signaling of mTOR.

Protective Role of Eurycoma longifolia Jack Root Extract Against High-Fat Diet Induced Testicular Damage in Sprague-Dawley Rats

“…It has been shown that HFD altered the carbohydrate metabolism, the testicular architecture and leads to spermatogenetic damage and impaired the fertility. 6,18,19 In the present study, serum testosterone, was comparable between normal diet and HFD animals, this in consent with Fernandez et al who observed analogous testosterone levels in HFD rats compared with standard chow fed rats. 20 Serum testosterone depletion accompanied with a reduction of sexual organ weight was observed in rats that fed on hypercaloric diet.…”

Statin use and survival outcomes in endocrine-related gynecologic cancers: A systematic review and meta-analysis

“…Statins also affect the proliferation of tumor cells in murine models of breast, colon, pancreatic, liver, and prostate cancers [47–50]. Additionally, statins can also stimulate inflammatory responses and anticancer immune surveillance via the phosphorylation of Akt and down-regulation of the mammalian target of rapamycin (mTOR) [51]. …”

Geranylgeraniol prevents statin-induced skeletal muscle fatigue without causing adverse effects in cardiac or vascular smooth muscle performance

“…37 Furthermore, reduced weight gain has been reported in high-fat diet-fed rats given fluvastatin, and this was also not concluded to be an adverse effect. 47 Accordingly, the lower body mass observed in the SIM-treated groups in the present study is not considered to be pathological.…”