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 has 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.
C57BL/6 female mice (10 weeks 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/day, 5 days/week for 12 weeks.
Our data showed that EXE ameliorated HFD/HF-induced weight gain, fasting blood glucose levels, and visceral fat gain. More importantly, while HFD/HF diet promoted cellular senescence, EXE reversed it evidenced by a reduction in the levels of p53, p21 and p16, beta-galactosidase (SA-β-gal), and lipofuscin. Furthermore, EXE prevented HFD/HF-induced neuroinflammation (e.g., TNF-α and IL-1β) by inhibiting toll like receptor 2 (TLR2) downstream signaling cascades (e.g., TRAF6, JNK and c-Jun) in parallel with reduced reactive glial cells. This anti-inflammatory effect of EXE was associated with reversion of HFD/HF-induced cellular oxidative stress.
Our study provides novel evidence that EXE-induced anti-senescence 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
Corresponding Author: 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, Florida, 32514, USA. Phone: 850-474-2596. Fax: 850-474-2106. e-mail: email@example.com
We declare that the results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. This project was supported by a grant from the University of West Florida through the Office of Research and Sponsored Programs (R0036 and R0062). The results of the present study do not constitute endorsement by ACSM. Conflict of interest. None
Accepted for publication: 10 April 2019.