Repository logo

Theses and Dissertations

Permanent URI for this collection

https://hdl.handle.net/10217/100356

Browse

Browsing Theses and Dissertations by Subject "AMPK"

Now showing 1 - 2 of 2
  • Thumbnail Image
    ItemOpen Access
    Hormonal controls of obesity in feeding and fasting hibernating mammals
    (Colorado State University. Libraries, 2010) Healy, Jessica, author; Florant, Gregory L., advisor; Kanatous, Shane B., 1968-, advisor; Ghalambor, Cameron K., committee member; Irlbeck, Nancy A., committee member
    Mammals that hibernate (hibernators) are intriguing models for the study of controls of food intake and adiposity due to their robust circannual cycle of obesity and anorexia. The pathways controlling these cycles in hibernators have not been fully elucidated. In order to clarify the relationships between various hormones, enzymes and metabolic factors, I examined endogenous and experimentally manipulated levels of several factors in hibernators kept under various physiological conditions, including short-term fasting in summer, long-term fasting in winter, and at low and high body temperature. I compared orexigenic factors (such as the hormone ghrelin and the enzyme AMP-activated protein kinase (AMPK)) with anorexigenic compounds (such as leptin and the enzyme acetyl CoA carboxylase (ACC)) at various times of the year and under experimentally manipulated conditions. Ghrelin is an orexigenic hormone produced by the stomach which increases food intake. Leptin is an anorexigenic hormone produced by white adipose tissue (WAT) which decreases food intake. Both of these hormones impact AMPK, a cellular-energy sensing enzyme that increases food intake and fatty acid oxidation through its inactivation of ACC. I found distinct seasonal profiles of these enzymes and hormones that correlated well with the observed life history characteristics of one species of hibernator, the golden-mantled ground squirrel (GMGS, Callospermophilus lateralis). In spring and summer, when GMGS are normophagic and lipogenic, the hormone profile of hibernators was much like non-hibernating rodents--AMPK and ghrelin increased with fasting, and injected ghrelin caused an increase in food intake with an associated increase in the active form of AMPK (pAMPK). In autumn, when GMGS are hyperphagic and lipogenic, circulating ghrelin concentrations were higher than at other times of the year, and release of leptin from WAT lagged behind fat mass to allow hyperphagic animals to become obese before hibernation. In winter, when GMGS were aphagic and lipolytic, AMPK and ACC activation were higher in torpid than in euthermic animals, circulating leptin concentrations were once again coupled with fat mass, ghrelin was still circulating in the blood, but at lower concentrations than during normophagic seasons, and circulating ghrelin was higher in euthermic than in torpid GMGS. This was the first published investigation of the hormone ghrelin in a true hibernator, and provides a potential explanation of the dramatic seasonal changes in food intake seen in mammals that hibernate.
  • Thumbnail Image
    ItemOpen Access
    Molecular regulation of growth and molting in decapod crustaceans
    (Colorado State University. Libraries, 2014) Mudron, Megan Reese, author; Mykles, Donald L., advisor; Garrity, Deborah M., committee member; Curthoys, Norman P., committee member
    The green shore crab, Carcinus maenas, is a highly invasive species that inhabits coastal temperate zones worldwide. The reaction of C. maenas to acute temperature change was determined in six tissues (heart, gill, thoracic ganglion, eyestalk ganglion, Y-organ, and claw muscle) using genetic markers for temperature-induced metabolic stress, including HSP70, AMPKγ, mTOR, and Rheb. Animals were exposed to temperatures between 5° and 30°C for 1 or 2 h. mRNA levels in six tissues were quantified by quantitative RT-PCR (qPCR). The results indicate that C. maenas tolerated a wide temperature range, requiring 2-h exposures at 5 °C and 30 °C to affect tissue-specific changes in gene expression. Cm-HSP70 expression was robustly increased at 30 °C in all tissues. Ecdysteroids produced from the molting gland (Y-organ or YO) induce molting in decapod crustaceans. Reduction in molt-inhibiting hormone (MIH) activates the YO and animals enter premolt. At mid-premolt, YOs transition to the committed state, during which ecdysteroid production increases further. In blackback land crab (Gecarcinus lateralis), a tropical decapod species, SB1431542, an inhibitor of Activin receptors, decreases hemolymph ecdysteroid titers in premolt animals, suggesting that an Activin-like transforming-growth factor (TGF-β) is produced by the activated YO and drives the transition of the YO to the committed state. Myostatin (Gl-Mstn) is an Activin-like factor that is highly expressed in skeletal muscle. Rapamycin lowers hemolymph ecdysteroid titers by inhibiting mTOR, which controls global translation of mRNA into protein. Endpoint RT-PCR established that Gl-Mstn was expressed in the YO, not just muscle tissue. YOs were harvested from intact (intermolt) animals and from animals at 1, 3, 5, 7, and 14 days post-ESA. Quantitative PCR was used to quantify the effects of molt induction by eyestalk ablation (ESA) on gene expression. Expression of mTOR components peaked at 3 days post-ESA, which is consistent with the increased activity required for activation of the YO. Gl-Mstn expression also peaked at 3 days post-ESA, which is before the transition to the committed state at 7 days post-ESA. These results indicate that mTOR components are involved in activation of the YO, and Mstn is involved in transitioning the YO to the committed state.