Title page for ETD etd-05032011-152922


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
Denbow, Donald Michael Committee Chair
Cline, Mark A. Committee Member
Denbow, Cynthia J. Committee Member
Siegel, Paul B. Committee Member
Wong, Eric A. 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) body

weight 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

iii

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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