Mitochondrial dysfunction is a contributing factor to the advancement of various diseases including obesity, diabetes, and cardiovascular disease. Impairment in mitochondria brings about a diminished mitochondrial number and oxidative capacity. Leucine is known to stimulate muscle protein synthesis through transcription and translation of nuclear DNA leading to increases in mitochondrial biogenesis and fatty acid oxidation. However, the effects of leucine on anabolic factors of the mitochondrial genome, during catabolic conditions are not known. <bold> PURPOSE </bold> : To determine if leucine supplementation alters the negative effects of a high fat (60%) diet (HFD) on the mitochondrial genome by measuring the gene expression of mitochondrial protein synthesis markers TFAM, mtIF2, and TUFM, and mitochondrial biogenesis regulatory factors PGC-1α and COX-IV. <bold> METHODS </bold : Male, Sprague-Dawley rats (n = 30 / dietary treatment) were fed either a control diet (C), control + leucine (CL), high-fat (HF), or high-fat + leucine (HFL) for 42 days. At the conclusion of 42 days, the soleus was extracted and used for analysis. Quantitative PCR was conducted to determine gene expression for PGC-1α, TFAM, mtIF2, TUFM, and COX-IV. <bold> RESULTS </bold>:: mtIF2 gene expression increased 4-fold (p < 0.05) and TFAM gene expression increased 5-fold, with a control diet supplemented with leucine, respectively. mtIF2 gene expression increased 4-fold (p < 0.05) in response to a HFD compared to normal chow. However, TUFM gene expression declined (p < 0.05) in response to a HFD with or without leucine. <bold> CONCLUSION</bold>:: Leucine supplementation did not stimulate an increase in TFAM, mtIF2, and TUFM when exposed to a HFD, but does however stimulate an increase of mitochondrial protein synthesis markers in normal conditions. Indicating enhanced mitochondrial protein synthesis with leucine supplementation, at least under normal conditions. TABLE OF CONTENTS Chapter 1Introduction........................................................................................... 1 Chapter 2Review of Literature................................................................. 3 Chapter 3Specific Aims..........................................................................19 Chapter 4Methods................................................................................22 Chapter 5Results...................................................................................25 Chapter 6Discussion..............................................................................30 References............................................................................................36 Appendix.............................................................................................43

https://scholarworks.uark.edu/cgi/viewcontent.cgi?article=3725&context=etd

The Effect of Leucine Supplementation on Biomarkers of Mitochondrial Biogenesis and Protein Synthesis in Soleus Muscle of Rats Fed a High-Fat Diet

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The Effect of Leucine Supplementation on Biomarkers of Mitochondrial Biogenesis and Protein Synthesis in Soleus Muscle of Rats Fed a High-Fat Diet