Obesity has become a prevalent global health issue, and recently it has been reported to be intimately associated with neuronal health. Obesity triggers peripheral inflammatory responses concomitant with neuroinflammation, elevated oxidative stress, and compromised autophagy. Intermittent fasting (IF) positively influences lowering body weight and improving the metabolic changes accompanying obesity. IF also has a beneficial impact on neuronal function; however, no studies have discussed this effect on high-fat diet (HFD)-induced cerebellar damage. This study examines the effect of IF on the cerebellum of HFD-fed rats. Male Wister Albino rats (n = 16) were fed HFD for 16 weeks (HFD group); half of them were subjected to IF alternating with HFD for 6 weeks starting at the 11th week till the end of the experiment (fasting + HFD group). The control group of rats (n = 8) was kept on a basal diet. The animals were euthanized after 16 weeks. Their tissue was harvested and processed for morphology using H&E, cresyl violet, and luxol fast stains, and immunohistochemical staining was carried out for inflammatory marker (TNF-α), gliosis marker (GFAP), and autophagy markers (LC3 II and P62). Oxidative stress markers (SOD, MDA) were measured, and protein expression of phosphorylated-AMP-activated protein kinase (p-AMPK) and phosphorylated-rapamycin complex (p-mTOR) in cerebellar tissue was detected via western blotting. IF mitigated HFD-induced cerebellar morphological changes, reduced cerebellar TNF-α expression, decreased oxidative stress markers, and balanced p-AMPK and p-mTOR with autophagy improvement. Moreover, a decrease in body weight and ameliorated obesity-induced metabolic changes in the serum levels of glucose, insulin, cholesterol, and triglyceride were seen. These observations suggest that IF can improve both peripheral and central changes prompted by HFD through attenuating inflammation, oxidative stress, and reestablishing the autophagy balance.
Keywords: Autophagy; Cerebellum; High-fat diet; Inflammation; Intermittent fasting; Oxidative stress.
© 2021 S. Karger AG, Basel.