Effect of muscle exercise on metabolic disturbance induced by ovariectomy alone or with diabetes mellitus in rats; targeting the role of PGC-1α and FNDC5 expression

Abstract

This study investigated the possible role of regular moderate exercise on type 2 diabetes mellitus in ovariectomized rats. Methods: 50 female albino rats divided into 5 groups; control sham operated sedentary (CSS), ovariectomized sedentary (OS), ovariectomized trained (OT), diabetic ovariectomized sedentary (DOS) and diabetic ovariectomized trained (DOT). At the end of the experiment body mass index and body weight gain percentage were calculated then serum was used for determination of levels of irisin, glucose, insulin, lipid profile, tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL1β), interleukin 4 (IL4), interleukin 10 (IL10), malondialdehyde (MDA) and reduced glutathione (GSH). Furthermore, gastrocnemius muscle biopsies were taken for determination of peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC-1α) and fibronectin type III domain-containing protein 5 (FNDC5) relative gene expressions. Results: induction of diabetes after bilateral ovariectomy further exacerbated the disturbed metabolic, inflammatory and oxidative statuses, indicated by increased BMI, body weight gain percentage, total cholesterol, LDL, glucose, insulin, HOMA-IR, TNF-α, IL-1β and MDA levels, and decreased HDL, IL4, IL10 and GSH levels, in addition to decreased Irisin level and PGC-1α and FNDC5 expressions in OS and DOS groups compared to CSS and OS groups respectively. On the other hand, regular moderate exercise significantly alleviated all these disturbances, in concomitance with improvement of the irisin level and PGC-1α and FNDC5 expressions in OT and DOT groups compared to OS and DOS groups respectively. Conclusion: muscle exercise improved the metabolic, inflammatory and oxidative disturbances induced by estrogen deficiency and aggravated by diabetes, possibly via increasing serum irisin.