Jake C. Parson1, Stephanie N. Vick1, Caleb W. Grote2, Janelle M. Ryals2, Douglas E. Wright2, & Brianne L. Guilford1. 1Southern Illinois University Edwardsville, Edwardsville, Illinois, 2University of Kansas Medical Center, Kansas City, Kansas; e-mail: jparson@siue.edu

Recent research has identified irisin as a novel protein that stimulates the “browning” of white adipose by inducing thermogenesis in white adipose via increased uncoupling protein 1 (UCP1) levels. Exercise, in a peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) dependent manner, increases the release of the irisin precursor, fibronectin type III domain-containing protein 5 (FNDC5), from muscle. Irisin holds potential as a novel pharmacotherapeutic that could be used in the treatment of obesity. Prior studies have assessed the effects of exercise on irisin and proteins upstream and downstream of its activation, but the effects of diet on irisin have not been investigated. PURPOSE: The aim of this study was to evaluate the effects of diet and exercise on FNDC5 and associated proteins. METHODS: C57BL/6 mice were randomized into three groups for the 4 week intervention: Mice were fed a standard diet (Std), a high-fat diet (HF), or fed a high-fat diet and housed individually with free access to a running wheel (HFEX). At the end of the 4 week intervention, mice were sacrificed, tissues were harvested, and protein levels were measured in the gastrocnemius muscle using western blots. RESULTS: Body weight, fasting glucose and insulin, and homeostatic model of insulin resistance (HOMA-IR) were significantly higher in HF compared to Std and HFEX after the 4 week intervention. There was a trend (p = 0.09) toward increased FNDC5 levels in HF compared to HFEX. UCP-1 levels were significantly lower in the HFEX compared to both Std and HF. There were no significant differences among groups in PGC-1α. CONCLUSION: Although there were no statistically significant differences in FNDC5 levels, the trend toward increased FNDC5 in HF compared to HFEX suggests increased FNDC5 may be a compensatory mechanism to offset HF diet-induced weight gain by increasing energy expenditure. Exercise prevented excess weight gain and metabolic derangements in HF fed mice, but these effects do not appear to be mediated by increased FNDC5 levels. Further investigation, including assessment of FNDC5, PGC1-α, and UCP1 levels in adipose from these mice is needed to confirm the effects of HF feeding on the FNDC5/irisin pathway.

Funding provided by Southern Illinois University Edwardsville Seed Grants for Transitional and Exploratory Projects.

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