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Endurance Exercise Prevents Metabolic Distress–induced Senescence in the Hippocampus

JANG, YONGCHUL; KWON, INSU; COSIO-LIMA, LUDMILA; WIRTH, CHRISTOPHER; VINCI, DEBRA M.; LEE, YOUNGIL

Medicine & Science in Sports & Exercise: October 2019 - Volume 51 - Issue 10 - p 2012–2024
doi: 10.1249/MSS.0000000000002011
BASIC SCIENCES
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Purpose Metabolic disorder such as obesity and type 2 diabetes caused by excess caloric intake is associated with an increased risk of neurodegenerative diseases. Endurance exercise (EXE) has been suggested to exert neuroprotective effects against the metabolic distress. However, the exact underlying molecular mechanisms responsible for the exercise-induced neuroprotection have not been fully elucidated. In this study, we investigated whether EXE-induced neuroprotection is associated with cellular senescence, neuroinflammation, and oxidative stress using a mouse model of obesity induced by a high-fat/high-fructose diet.

Methods C57BL/6 female mice (10 wk old) were randomly divided to three groups: normal chow diet group (CON, n = 11), high-fat diet/high-fructose (HFD/HF) group (n = 11), and high-fat diet/high-fructose + endurance exercise (HFD/HF + EXE) group (n = 11). HFD/HF + EXE mice performed treadmill running exercise for 60 min·d−1, 5 d·wk−1 for 12 wk.

Results Our data showed that EXE ameliorated HFD/HF-induced weight gain, fasting blood glucose levels, and visceral fat gain. More importantly, HFD/HF diet promoted cellular senescence, whereas EXE reversed it, evidenced by a reduction in the levels of p53, p21, p16, beta-galactosidase (SA-β-gal), and lipofuscin. Furthermore, EXE prevented HFD/HF-induced neuroinflammation (e.g., tumor necrosis factor-α and interleukin-1β) by inhibiting toll-like receptor 2 downstream signaling cascades (e.g., tumor necrosis factor receptor–associated factor 6, c-Jun N-terminal kinase, and c-Jun) in parallel with reduced reactive glial cells. This anti-inflammatory effect of EXE was associated with the reversion of HFD/HF-induced cellular oxidative stress.

Conclusion Our study provides novel evidence that EXE-induced antisenescence against metabolic distress in the hippocampus may be a key neuroprotective mechanism, preventing neuroinflammation and oxidative stress.

Molecular and Cellular Exercise Physiology Laboratory, Department of Movement Sciences and Health, Usha Kundu, MD College of Health, University of West Florida, Pensacola, FL

Address for correspondence: Youngil Lee, Ph.D., Molecular and Cellular Exercise Physiology Laboratory, Department of Movement Sciences and Health, Usha Kundu, MD College of Health, University of West Florida, 11000 University Pkwy, Bldg. 72, Pensacola, FL 32514; E-mail: ylee@uwf.edu.

Submitted for publication February 2019.

Accepted for publication April 2019.

Online date: April 17, 2019

© 2019 American College of Sports Medicine