Studies conducted for this dissertation utilized a rodent model exposed to single or multiple short duration heat loads in an effort to: 1) elucidate the changes in energy metabolism occurring at the tissue and whole-body level in response to hyperthermia, 2) characterize specific aspects of glucose utilization and hepatic glucose production following a heat load and 3) determine if aspects of mitochondrial function and/or dysfunction might play a role in the metabolic changes that occur in response to heat stress. Study 1 was conducted to determine if rodents exposed to heat stress shared similarities using a bovine heat stress model. Specifically, we were interested in identifying changes in blood metabolites and hormones, as well as gene expression and protein abundance of enzymes associated with energy metabolism in skeletal muscle (type I and type II), liver and adipose tissue. Previous bovine data indicates glucose may be preferentially utilized during heat stress, suggesting alterations in energy metabolism. This study provided evidence that tissue-specific changes occur in response to a heat load and that full glucose oxidation might be reduced, specifically in skeletal muscle where abundance of PDK4 mRNA was increased. Within skeletal muscle, glucose transporters (GLUTs 1 and 4) also tended to be increased in rats exposed to a heat load. Increases in skeletal muscle AMPK-α and PGC-1α as well as increased expression of energy substrate transporters suggests heat stress may impose a cellular energy deficit and/or increased energy demands which subsequently leads to changes in energy metabolism. Few changes were noted in either hepatic or adipose tissue in response to acute heat stress in this pilot study. Study aim of Chapter 3 was to further characterize the effects of heat stress on energy metabolism at the tissue and whole-body level in rats exposed to either 1 or 2 bouts of heat. Rats exposed to a 6 h heat load tended to have higher plasma glucose but reduced insulin levels, compared to thermal neutral controls, suggesting decreased glucose uptake or increased hepatic glucose output. Additionally, although heat stress likely increases whole-body energy demand, plasma NEFA levels were blunted in the early hours following onset of heat, suggesting increased adipocyte insulin sensitivity. Gene expression of enzymes associated with oxidative energy metabolism were increased in the TA (which is comprised primarily of glycolytic muscle fibers) following 2 bouts and in liver following a single bout of heat, while expression of oxidative enzymes were decreased within the soleus (a primarily oxidative muscle type). AMPK mRNA was increased following a single bout of heat in hepatic tissue and after 2 bouts of heat in type I skeletal muscle. AMPK mRNA abundance remained the same following 1 bout but was reduced following 2 bouts of heat within type II skeletal muscle. In the TA, phosphorylated AMPK protein abundance was reduced by HS. Abundance of PGC-1α mRNA was increased in types I and II skeletal muscle but was only numerically increased in liver following heat exposure. These data suggest differences at the transcription level in how heat effects energy metabolism within types I and II skeletal muscle as well as between muscle and hepatic tissue and also suggests a cellular attempt to increase energy production (by all mechanisms) in response to heat exposure. Study 3 (Chapter 4) focused on the effect of a heat load on glucose utilization in skeletal muscle and hepatic glucose production capacity. Similar to study 1, PDK4 expression was increased in types I and II skeletal muscle, while PDK2 expression was increased in hepatic tissue. Within skeletal muscle, increases in PDK expression paralled the increased protein abundance of PDHE1α following heat exposure, implying a decrease in oxidative glucose metabolism. Within the liver, protein abundance of PDH-E1α was reduced following a single heat load, but returned to TN levels after a 2nd heat exposure, suggesting that glucose oxidative metabolism is increased above normal levels after an initial heat exposure, but reduced following multiple heat bouts. Hepatic mRNA abundance for gluconeogenic enzymes were increased, implying an increase in hepatic glucose output capacity. The purpose of Study 4 (Chapter 5) was to determine if heat stress elicits changes on mitochondrial function/dysfunction (i.e. oxidative stress), that may account for changes observed in energy metabolism. Expression of genes associated with antioxidant defense were increased by heat stress, but differed between types I and II skeletal muscle as well as between muscle, hepatic tissue and WBCs. The abundance of mRNA for antioxidant enzymes was increased the greatest, and expression of DNA repair enzymes were also upregulated the most within hepatic tissue due to heat exposure, suggesting either increased damage at the level of hepatocytes or greater defensive capacity following an environmental insult. Taken together, this data provides evidence that heat alters energy metabolism, but these changes are tissue-specific and may be reflective of where damage is occurring, or which tissues are able to adapt and/or compensate for increased energy demands imposed by an environmental insult.
| Identifer | oai:union.ndltd.org:arizona.edu/oai:arizona.openrepository.com:10150/194613 |
| Date | January 2010 |
| Creators | Sanders, Sara Ray |
| Contributors | Rhoads, Robert P., Baumgard, Lance H., Rhoads, Michelle L., Limesand, Sean W., Duff, Glenn C. |
| Publisher | The University of Arizona. |
| Source Sets | University of Arizona |
| Language | English |
| Detected Language | English |
| Type | text, Electronic Dissertation |
| Rights | Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author. |
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