Please use this identifier to cite or link to this item:
http://hdl.handle.net/11375/17325
Title: | Molecular Mechanism(s) of Sex Differences in Lipid Metabolism in Human Skeletal Muscle |
Authors: | Maher, Amy C. |
Advisor: | Tarnopolsky, Mark A. |
Department: | Medical Sciences |
Keywords: | differences, molecular, mechanisms, lipid, metabolism, muscle |
Publication Date: | Sep-2009 |
Abstract: | <p> It is well understood that compared with men, women are better able to withstand starvation, have better ultra-endurance capacity, oxidize more fat during endurance exercise, and are more resistant to fat oxidation defects i.e. diet-induced insulin resistance. However, the mechanism(s) for the observed sex differences are unknown. It was my hypothesis that women have greater fat oxidation capacity in skeletal muscle than men.</p> <p> The objectives of my thesis were to determine the mechanism(s) by which women oxidize more lipids; including the role of estrogen as a possible regulator. The most significant findings were that: 1) mRNA for fatty acid oxidation genes are higher in women compared with men, which was confirmed by Stringent Affymetrix GeneChip array analysis, combined with RT-PCR (chapter 2); 2) long-chain acyl-CoA dehydrogenase in human skeletal muscle is not quantifiable despite the majority (90%) of fatty acids oxidized during exercise are long-chain fatty acids (chapter 3); 3) β-oxidation enzymes: tri-functional protein alpha, very long chain acyl-CoA dehydrogenase, and medium chain acyl-CoA dehydrogenase are significantly higher in women compared with men (chapter 4); 4) Acute (8 days) 17β-estradiol supplementation in men significantly increased protein content of β-oxidation enzymes in skeletal muscle, possibly through the regulation of PGC-1α and microRNA (chapter 5).</p> <p> In conclusion, my data provided novel insights into the enhanced ability of women to oxidize fat under periods of metabolic stress by showing that: 1) women are transcriptionally (mRNA) "primed" for known physiological differences in metabolism; 2) women have more protein content of the major enzymes involved in long and medium chain fatty acid oxidation; 3) E2 partially regulates lipid metabolism in skeletal muscle by pre-translational modifications of factors involved in β-oxidation. These findings contribute to the molecular understanding of sex differences in substrate utilization.</p> |
URI: | http://hdl.handle.net/11375/17325 |
Appears in Collections: | Open Access Dissertations and Theses |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
Maher_Amy_C._2009:09_Ph.D..pdf | 7.96 MB | Adobe PDF | View/Open |
Items in MacSphere are protected by copyright, with all rights reserved, unless otherwise indicated.