J Neuroendocrinol. 2016 Mar 16. Epub 2016 Mar 16. PMID: 26991447
Eun-Bum Kang
Obesity contributes to systemic inflammation, associated with various pathogenesis of neurodegenerative diseases. Growing evidence has demonstrated that endurance exercise (EE) mitigate obesity-induced brain inflammation. However, exercise-mediated anti-inflammatory mechanisms remain largely unknown. We investigated how treadmill exercise (TE) reverses obesity-induced brain inflammation, mainly focusing on toll-like receptor-4 (TLR-4)-dependent neuroinflammation in the obese rat brain following 20 weeks of high fat diet (HFD). TE in HFD-fed rats resulted in a significant lowering in HOMA-IR, AUC for glucose and abdominal visceral fat and improved working memory ability in a passive avoidance task relative to sedentary in HFD-fed rats with the exception of body weight. More importantly, TE revoked the increase in HFD-induced proinflammatory cytokines (TNFα and IL-1β) and COX-2, which parallels with reduction in TLR-4 and its downstream proteins, MyD88 and TRAF6 and phosphorylation of TAK-1, IkBα and NF-κB. Moreover, TE reduced an indicator of microglia activation, IBA-1 as well as decreased GFAP, an indicator of gliosis formed by activated astrocytes in the cerebral cortex and the hippocampal dentate gyrus (DG), compared to HFD-fed sedentary rats. Finally, EE upregulated the expression of anti-apoptotic protein, Bcl-2 and suppressed the expression of pro-apoptotic protein, Bax in the hippocampus compared to HFD-fed sedentary rats. Taken together, these data suggest that TE may exert neuroprotective effects by mitigating the production of proinflammatory cytokines by inhibiting the TLR4 signaling pathways. This study suggest that the unique combination of TE's beneficial effects on the restoration of blood profile and anti-inflammatory and anti-apoptotic effects on cognitive function should inspire further investigation of its therapeutic potential for metabolic disorder and neurodegenerative diseases. This article is protected by copyright. All rights reserved.