GENETIC OVEREXPRESSION OF PGC-1α1 DOES NOT PROTECT AGAINST LIPID-INDUCED DECREMENTS IN RUNNING CAPACITY, REGARDLESS OF GREATER OXIDATIVE PHENOTYPE
Kyle W. Turner1, Megan E. Rosa-Caldwell1, Jacob L. Brown1, David E. Lee1, Thomas A.
Blackwell1, Lemuel A. Brown1, Richard A. Perry Jr.1, Wesley S. Haynie1, Tyrone A. Washington1, Nicholas P. Greene1 1University of Arkansas
Obesity and lack of cardiorespiratory fitness continue to remain major public health concerns. Lipid-overload is known to diminish aerobic capacity under sedentary conditions. Aerobic fitness is protective against lipid-induced degradations, which is largely mediated by mitochondrial function; however, it is unclear if artificially increasing mitochondrial content will promote similar protections. PURPOSE: To assess how genetic overexpression of PGC-1α1 affects muscle oxidative phenotype and aerobic fitness after a period of Western Diet feeding with(out) voluntary physical activity. METHODS: ~40 Muscle Creatine Kinase-PGC-1α1 transgenic (TG) and wildtype (WT) littermates were placed on Western Diet (WD) at 8 wks of age and allowed to chow ad libitum throughout. At 12 wks of age, animals were randomly assigned to voluntary wheel running (VWR) or sedentary (SED) conditions. At 16 wks of age, mice were euthanized and hindlimb muscles collected. At 7, 11, and 15 wks of age, animals were administered graded exercise tests (GXT) to evaluate aerobic fitness. To assess muscle oxidative phenotype, tibialis anterior muscles were sectioned and stained for succinate dehydrogenase (SDH). Number of myofibers positive for SDH were then counted and expressed as percent of total myofibers counted. Data was analyzed by repeated measures or cross-sectional ANOVA as appropriate, significance was determined at p<0.05. RESULTS: Gastrocnemius, plantaris, and soleus muscles were heavier (5%, 11%, and 20% respectively) in VWR groups compared to SED and EDL was lighter (~10%) in TG compared to WT animals. For GXT, TG animals ran ~35% longer compared to WT regardless of time point. Distances run progressively lowered in SED animals across time (~30%) regardless of genotype, with no difference in VWR animals across time points. At 15 wks of age, VWR ran ~45% longer compared to SED, regardless of genotype. TG animals had 32.6% more SDH positive stained fibers compared to WT animals, with no effect of exercise. CONCLUSION: Under conditions of lipid overload, genetic overexpression of PGC-1α1 results in a greater oxidative phenotype and longer GXT distances compared to WT animals. However, exercise appears to have a greater benefit than PGC-1α1 overexpression in respect to preventing loss of running capacity under lipid overloaded conditions.
Turner, KW; Rosa-Caldwell, ME; Brown, JL; Lee, DE; Blackwell, TA; Brown, LA; Perry Jr., RA; Haynie, WS; Washington, TA; and Greene, NP
"GENETIC OVEREXPRESSION OF PGC-1α1 DOES NOT PROTECT AGAINST LIPID-INDUCED DECREMENTS IN RUNNING CAPACITY, REGARDLESS OF GREATER OXIDATIVE PHENOTYPE,"
International Journal of Exercise Science: Conference Proceedings: Vol. 11:
4, Article 47.
Available at: https://digitalcommons.wku.edu/ijesab/vol11/iss4/47