title: Neuroprotective Effects of Endurance Exercise Against High-Fat Diet-Induced Hippocampal Neuroinflammation.
abstract: Obesity contributes to systemic inflammation, which is associated with the varied pathogenesis of neurodegenerative diseases. Growing evidence has demonstrated that endurance exercise (EE) mitigates 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 after 20 weeks of a high-fat diet (HFD). TE in HFD-fed rats resulted in a significant lowering in the homeostasis model assessment of insulin resistance index, the area under the curve for glucose and abdominal visceral fat, and also improved working memory ability in a passive avoidance task relative to sedentary behaviour in HFD-fed rats, with the exception of body weight. More importantly, TE revoked the increase in HFD-induced proinflammatory cytokines (tumour necrosis factor α and interleukin-1β) and cyclooxygenase-2, which is in parallel with a reduction in TLR-4 and its downstream proteins, myeloid differentiation 88 and tumour necrosis factor receptor associated factor 6, and phosphorylation of transforming growth factor β-activated kinase 1, IkBα and nuclear factor-κB. Moreover, TE reduced an indicator of microglia activation, ionised calcium-binding adapter molecule-1, and also decreased glial fibrillary acidic protein, an indicator of gliosis formed by activated astrocytes in the cerebral cortex and the hippocampal dentate gyrus, compared to HFD-fed sedentary rats. Finally, EE up-regulated 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 as a result of mitigating the production of proinflammatory cytokines by inhibiting the TLR4 signalling pathways. The results of the present study suggest that the unique combination of the beneficial effects of TE on the restoration of the blood profile and the anti-inflammatory and anti-apoptotic effects on cognitive function should inspire further investigations into its therapeutic potential for metabolic disorders and neurodegenerative diseases.
authors.affiliation: Exercise Biochemistry Laboratory, Korea National Sport University, Seoul, Korea.
authors.forename: E-B
authors.initials: EB
authors.lastname: Kang
authors.affiliation: Exercise Biochemistry Laboratory, Korea National Sport University, Seoul, Korea.
authors.forename: J-H
authors.initials: JH
authors.lastname: Koo
authors.affiliation: Exercise Biochemistry Laboratory, Korea National Sport University, Seoul, Korea.
authors.forename: Y-C
authors.initials: YC
authors.lastname: Jang
authors.affiliation: Department of Marine Sports, University of Han-Seo, Seosansi, Korea.
authors.forename: C-H
authors.initials: CH
authors.lastname: Yang
authors.affiliation: Exercise Biochemistry Laboratory, University of West Florida, Pensacola, FL, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Exercise Biochemistry Laboratory, University of West Florida, Pensacola, FL, USA.
authors.forename: L M
authors.initials: LM
authors.lastname: Cosio-Lima
authors.affiliation: Exercise Biochemistry Laboratory, Korea National Sport University, Seoul, Korea.
authors.forename: J-Y
authors.initials: JY
authors.lastname: Cho
mesh_terms: D000818:Animals; D017209:Apoptosis; D001253:Astrocytes / Q000378:metabolism; D001835:Body Weight; D002540:Cerebral Cortex / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D004660:Encephalitis / Q000378:metabolism* / Q000517:prevention & control*; D006624:Hippocampus / Q000378:metabolism*; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000378:metabolism; D008297:Male; D018696:Neuroprotective Agents; D010807:Physical Endurance; D017207:Rats, Sprague-Dawley; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D018696:Neuroprotective Agents; D051197:Toll-Like Receptor 4
keywords: TRL-4 signal transduction; memory; neuroinflammation; obesity; treadmill exercise