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http://hdl.handle.net/11375/14004
Title: | Molecular mechanisms of sex-based differences in substrate utilization during endurance exercise in human skeletal muscle |
Authors: | Fu, Minghua |
Advisor: | Tarnopolsky, Mark A |
Department: | Kinesiology |
Keywords: | Kinesiology;Kinesiology |
Publication Date: | May-2007 |
Abstract: | <p>Introduction: A higher rate of fat and lower rates of carbohydrate and protein oxidation are often observed during endurance exercise in women vs. men at the same relative workload. 17~-estradiol (E2) supplementation increases the oxidation of lipid, and reduces the oxidation of carbohydrate and amino acids in men. Women have a higher area percentage (%) of type I skeletal muscle fibers as compared with men. Consequently, we hypothesized that (i) sex, menstrual cycle phase and E2 would influence basal and exercise induced mRNA content for genes involved in substrate metabolism in human skeletal muscle; and (ii) sex would influence the basal mRNA content for genes involved in the determination of muscle fiber type. Methods: For studies concerning substrate selective utilization, 12 men and 12 women had muscle biopsies taken from their vastus lateralis before and after a 90 min bout of cycle exercise at 65 % V02peak. In a repeated measures design, men were randomly allocated to both E2 and placebo. Women were studied in the mid-follicular (FOL) and mid-luteal (LUT) phases ('" 2 wk apart). For studies concerning muscle fiber determination, a total of 24 women and 22 men had muscle biopsies taken from their vastus lateralis at rest. Twelve of the women were studied in mid-LUT, and 12 were studied in both the mid-FOL and mid-LUT, phases of the menstrual cycle. mRNA content was determined using TaqMan® real-time RT-PCR. Muscle fiber composition in 12 men and 12 women was determined from ATPase staining. Results: Exercise increased (P < 0.05) the mRNA content of peroxisome proliferator activated receptor gamma coactivator-1 alpha (PGC- 1a) (men, LUT) , cytosol fatty acid binding protein (FABPc) (men, FOL, LUT), carntine palmitoyltransferase I (CPTI) (men, LUT), long chain acyl-CoA dehydrogenase (LCAD) (LUT), hexokinase II (HKIl), asparatate aminotransferase (AST) and glucose transporter 4 (GLUT4) (men and women). Women had a higher (P ~ 0.05) mRNA content of membrane bound fatty acid transport protein 1 (F ATm), F ABPc, sterol regulatory element - binding protein 1 c (SREBP-l c) and mitochondrial glycerol phosphate acyltransferase (mtGPAT) (FOL, LUT), peroxisome proliferator activated receptor alpha (PPARa) (FOL), CPTI (FOL), LCAD (FOL), trifunctional protein alpha subunit (TFPa) (LUT), HKIl (FOL) and branched-chain 2-oxo acid dehydrogenase kinas (BCOADK) (FOL, LUT) pre- and post- exercise, peroxisome proliferator activated receptor delta (PPAR8) (FOL) and GLUT4 (FOL) at rest, and PPARa ( LUT) and LCAD (LUT) after exercise, and lower mRNA content for phosphofructokinase (PFK) (LUT) pre- and postexercise, than men. FOL women had a higher (P < 0.05) PPAR8, LeAD and glycogen phosphorylase and lower glycogenin mRNA content pre- and post- exercise, and tended to have higher GLUT4 mRNA content (P = 0.056) at rest, vs. LUT women. Postexercise FABPc mRNA content increased to a greater extent in LUT vs. FOL phase (P = 0.0001). E2 increased mRNA content of PPARa, CPTI, SREBP-lc, mtGPAT, LCAD, TFP-a, GLUT4 and GS-l (P < 0.05) in men at rest and during exercise, and PPAR8 at rest (P < 0.05). E2 attenuated the exercise induced increase in PGC-la mRNA content (P < 0.05). Women had lower mean area of individual fibers for type Ila and type Ilx, and a higher area % of type I fibers and lower area % of type II fibers vs. men (P < 0.05). Women had higher mRNA content for myosin heavy chain I (MHCI) (FOL, LUT, P ~ 0.05) and PPAR8 (FOL, P < 0.05), and a similar mRNA content of myosin heavy chain Ila (MHCIla), myosin heavy chain Ilx (MHCIlx), peroxisome proliferator activated receptor gamma coactivator-l alpha (PGC-l a), myostatin and PP AR8 (LUT), vs. men at rest. FOL women had a higher mRNA content of PPAR8 than LUT women (P = 0.0007). Menstrual cycle phase did not significantly alter the mRNA content of MHCI, PGC-l a or myostatin. Conclusions and Significance: We have comprehensively evaluated the effect of sex, acute endurance exercise, menstrual cycle and E2 on the content of mRNA species involved in substrate turnover in human skeletal muscle and found these changes directionally support a higher fat oxidation and lower protein oxidation in women vs. men. We have also evaluated the sex influences on the mRNA content of the genes involved in muscle fiber determination and found the change in PPAR8 mRNA content supports a greater area % of type I fibers in women than men.</p> |
URI: | http://hdl.handle.net/11375/14004 |
Identifier: | opendissertations/8836 9913 5334794 |
Appears in Collections: | Open Access Dissertations and Theses |
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