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Article Title

ABERRANT REGULATION OF MITOCHONDRIAL BIOGENESIS AND CONTENT FOLLOWING LIFESTYLE PHYSICAL ACTIVITY IN WESTERN DIET FED MICE

Abstract

Jordyn N. Henry, David E. Lee, Megan E. Rosa, Jacob L. Brown, Lemuel A. Brown, Richard A. Perry Jr., Tyrone A. Washington & Nicholas P. Greene

University of Arkansas, Fayetteville, Arkansas

The purpose of this study was to examine the gene expressions Cox4 and Pgc-1a in mice. By looking at these genetic markers we are able to investigate the regulation of biogenesis and mitochondrial quantity affected by aerobic exercise and obesity. PURPOSE: To examine the mitochondrial quantity and the regulation of mitochondria biogenesis in obese and lean controls after aerobic exercise. METHODS: Forty C57BL6/J male mice beginning at eight weeks of age were separated into two categories twenty on normal chow (NC) and twenty on Western diet (WD, 42% kcal by fat plus 1.5g/kg cholesterol). After four weeks of diet, ten mice from each diet group were allowed physical activity by voluntary wheel running (VWR), while the remaining ten were kept sedentary (SED). Following four weeks of exercise or sedentary lifestyles the mice were euthanized, and mixed fiber gastrocnemius muscles were removed and immediately frozen in liquid nitrogen. The muscle samples were homogenized and RNA isolated, cDNA synthesized, and finally, analyzed for Cox4 and Pgc1a gene expressions via Real Time PCR. Data were analyzed by 2X2 ANOVA (diet [NC vs. WD] X activity [SED vs. VWR]) with α set at P<0.05.RESULTS: Pgc-1a was significantly elevated (P < 0.05) in NC VWR, WD SED and WD VWR groups compared to NC SED; relative levels of Pgc-1a were 1±0.45, 1.64±0.35, 1.40±0.40, and 1.49±0.25 for NC SED, NC VWR, WD SED, and WD VWR, respectively. Cox4 was significantly elevated (P < 0.05) by VWR and diet independent of one another, relative levels were 1.00±0.48, 1.82±1.08, 1.77± 0.61, 2.27±0.58 for NC SED, NC VWR, WD SED, and WD VWR, respectively. CONCLUSION: The body’s natural response to exercise is to induce mitochondrial biogenesis, which is shown with Pgc-1a, ultimately improving metabolic health. We see an increase in Pgc-1a gene expression with exercise in NC mice. While WD mice show already increased Pgc-1a gene expression with diet only. Cox4 gene expression was elevated by WD and increased following training regardless of diet. These data demonstrate aberrant mitochondrial biogenesis and content regulation following WD.

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