Type of Document Dissertation Author Xu, Pingwen Author's Email Address pingwenx@vt.edu URN etd-05032011-152922 Title Involvement of AMP-activated protein kinase in differential regulation of appetite between lines of chickens selected for low or high juvenile body weight Degree PhD Department Animal and Poultry Sciences Advisory Committee
Advisor Name Title D. Michael Denbow Committee Chair Cynthia J. Denbow Committee Member Eric A. Wong Committee Member Mark A. Cline Committee Member Paul B. Siegel Committee Member Keywords
- ghrelin
- food intake
- chicken
- AMPK
- obestatin
Date of Defense 2011-04-21 Availability restricted Abstract This study was to determine (1) if genetic selection for high (HWS) or low (LWS) bodyweight in chickens has altered the hypothalamic AMP-activated protein kinase (AMPK)
system and (2) if this alteration contributes to the dissimilar feeding response to various
appetite modulators between HWS and LWS lines. Compared to HWS, LWS chickens
had higher levels of AMPK α and acetyl-CoA carboxylase (ACC) phosphorylation,
which was caused by upregulation of the upstream factor calcium/calmodulin-dependent
protein kinase kinase 2 (CAMKK β). There was greater mRNA expression of carnitine
palmitoyltransferase I (CPT1), leptin receptor (LEPR) and neuropeptide Y (NPY) and
less mRNA expression of ACC α, fatty acid synthase (FAS), fat mass and obesity
associated gene (FTO), pro-opiomelanocortin (POMC) and orexin in LWS than HWS
chickens. At 5 days of age, intracerebroventricular (ICV) injection of AICAR, 5-amino-
4-imidazolecarboxamide riboside, caused a quadratic dose-dependent decrease in food
intake in LWS but not HWS chicks. Compound C, (6-(4-(2-piperidin-1-yl-ethoxy)-
phenyl))-3-pyridin-4-yl-pyrazolo(1,5-a)-pyrimidine, caused a quadratic dose-dependent
increase in food intake in HWS but not LWS chicks. The anorexigenic effect of AICAR
in LWS chicks and orexigenic effect of Compound C in HWS chicks resulted from either
activation or inhibition of other kinase pathways separate from AMPK. There is a lower
threshold for the anorexigenic effect of ghrelin in LWS than HWS chicks, which was
associated with differential hypothalamic AMPK signaling. ICV injection of ghrelin
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inhibited corticotrophin-releasing hormone (CRH), 20-hydroxysteroid dehydrogenase
(20HSD), glucocorticoid receptor (GR), CPT1 and FTO expression in LWS but not HWS
chicks. Additionally, the hypothalamic mRNA level of ghrelin was significantly higher in
LWS than HWS chicks, which may also contribute to the differential threshold response
to ghrelin in these two lines. Obestatin caused a linear dose-dependent increase in food
intake in HWS but not LWS chicks. The orexigenic effect of obestatin in HWS chicks
was not associated with altered AMPK. Obestatin inhibited LEPR and FTO expression in
HWS but not LWS chicks. Thus, selection for body weight may alter the hypothalamic
response to ghrelin by the AMPK pathway, CRH pathway, CPT1 and FTO, and to
obestatin by LEPR and FTO.
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