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The effect of placental restriction on insulin signaling and lipogenic pathways in omental adipose tissue in the postnatal lamb

Published online by Cambridge University Press:  13 June 2013

S. Lie ,
J. A. Duffield ,
I. C. McMillen ,
J. L. Morrison ,
S. E. Ozanne ,
C. Pilgrim  and
B. S. Muhlhausler
S. Lie
Affiliation:
Early Origins of Adult Health Research Group, School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, The University of South Australia, Adelaide, Australia
J. A. Duffield
Affiliation:
Early Origins of Adult Health Research Group, School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, The University of South Australia, Adelaide, Australia
I. C. McMillen
Affiliation:
Early Origins of Adult Health Research Group, School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, The University of South Australia, Adelaide, Australia
J. L. Morrison
Affiliation:
Early Origins of Adult Health Research Group, School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, The University of South Australia, Adelaide, Australia
S. E. Ozanne
Affiliation:
Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Cambridge, UK
C. Pilgrim
Affiliation:
Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Cambridge, UK
B. S. Muhlhausler*
Affiliation:
Early Origins of Adult Health Research Group, School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, The University of South Australia, Adelaide, Australia
*
*Address for correspondence: Dr Beverly Muhlhausler, FOOD Plus Research Centre, School of Agriculture, Food and Wine, The University of Adelaide, Adelaide 5005, Australia. (Email [email protected])
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Abstract

Intrauterine growth restriction (IUGR) followed by accelerated growth after birth is associated with an increased risk of abdominal (visceral) obesity and insulin resistance in adult life. The aim of the present study was to determine the impact of IUGR on mRNA expression and protein abundance of insulin signaling molecules in one of the major visceral fat depots, the omental adipose depot. IUGR was induced by placental restriction, and samples of omental adipose tissue were collected from IUGR (n = 9, 5 males, 4 females) and Control (n = 14, 8 males, 6 females) neonatal lambs at 21 days of age. The mRNA expression of the insulin signaling molecules, AMP-kinase (AMPK) and adipogenic/lipogenic genes was determined by qRT-PCR, and protein abundance by Western Blotting. AMPKα2 mRNA expression was increased in male IUGR lambs (0.015 ± 0.002 v. 0.0075 ± 0.0009, P < 0.001). The proportion of the AMPK pool that was phosphorylated (%P-AMPK) was lower in IUGR lambs compared with Controls independent of sex (39 ± 9% v. 100 ± 18%, P < 0.001). The mRNA expression and protein abundance of insulin signaling proteins and adipogenic/lipogenic genes was not different between groups. Thus, IUGR is associated with sex-specific alterations in the mRNA expression of AMPKα2 and a reduction in the percentage of the total AMPK pool that is phosphorylated in the omental adipose tissue of neonatal lambs, before the onset of visceral obesity. These molecular changes would be expected to promote lipid accumulation in the omental adipose depot and may therefore contribute to the onset of visceral adiposity in IUGR animals later in life.

Keywords

adipose tissuefetal programminggrowthIUGRplacental restriction
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 4 , Issue 5 , October 2013 , pp. 421 - 429
Copyright
Copyright © Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2013 

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