Document Detail

Maternal overnutrition suppresses the phosphorylation of 5'-AMP-activated protein kinase in liver, but not skeletal muscle, in the fetal and neonatal sheep.
MedLine Citation:
PMID:  18784329     Owner:  NLM     Status:  MEDLINE    
Epidemiological studies have shown that infants exposed to an increased supply of nutrients before birth are at increased risk of type 2 diabetes in later life. We have investigated the hypothesis that fetal overnutrition results in reduced expression and phosphorylation of the cellular fuel sensor, AMP-activated kinase (AMPK) in liver and skeletal muscle before and after birth. From 115 days gestation, ewes were fed either at or approximately 55% above maintenance energy requirements. Postmortem was performed on lamb fetuses at 139-141 days gestation (n = 14) and lambs at 30 days of postnatal age (n = 21), and liver and quadriceps muscle were collected at each time point. The expression of AMPKalpha1 and AMPKalpha2 mRNA was determined by quantitative RT-PCR (qRT-PCR). The abundance of AMPKalpha and phospho-AMPKalpha (P-AMPKalpha) was determined by Western blot analysis, and the proportion of the total AMPKalpha pool that was phosphorylated in each sample (%P-AMPKalpha) was determined. The ratio of AMPKalpha2 to AMPKalpha1 mRNA expression was lower in fetuses compared with lambs in both liver and muscle, independent of maternal nutrition. Hepatic %P-AMPKalpha was lower in both fetuses and lambs in the Overfed group and %P-AMPKalpha in the lamb liver was inversely related to plasma glucose concentrations in the first 24 h after birth (r = 0.73, P < 0.025). There was no effect of maternal overnutrition on total AMPKalpha or P-AMPKalpha abundance in liver or skeletal muscle. We have, therefore, demonstrated that AMPKalpha responds to signals of increased nutrient availability in the fetal liver. Suppression of hepatic AMPK phosphorylation may contribute to increased glucose production, and basal hyperglycemia, present in lambs of overfed ewes in early postnatal life.
L K Philp; B S Muhlhausler; A Janovska; G A Wittert; J A Duffield; I C McMillen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-09-10
Journal Detail:
Title:  American journal of physiology. Regulatory, integrative and comparative physiology     Volume:  295     ISSN:  0363-6119     ISO Abbreviation:  Am. J. Physiol. Regul. Integr. Comp. Physiol.     Publication Date:  2008 Dec 
Date Detail:
Created Date:  2008-12-10     Completed Date:  2009-01-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901230     Medline TA:  Am J Physiol Regul Integr Comp Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  R1982-90     Citation Subset:  IM    
Early Origins of Adult Health Research Group, Sansom Institute, University of South Australia, Adelaide 5001, Australia.
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MeSH Terms
AMP-Activated Protein Kinases / genetics,  metabolism*
Animals, Newborn
Blood Glucose / metabolism
Fatty Acids, Nonesterified / blood
Fetus / enzymology
Gene Expression Regulation, Developmental
Gene Expression Regulation, Enzymologic
Gestational Age
Insulin / blood
Leptin / blood
Liver / embryology,  enzymology*
Maternal Nutritional Physiological Phenomena*
Overnutrition / embryology,  enzymology*
Prenatal Exposure Delayed Effects*
Protein Subunits
Quadriceps Muscle / embryology,  enzymology*
RNA, Messenger / metabolism
Reg. No./Substance:
0/Blood Glucose; 0/Fatty Acids, Nonesterified; 0/Leptin; 0/Protein Subunits; 0/RNA, Messenger; 11061-68-0/Insulin; EC Protein Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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