Hostname: page-component-848d4c4894-pjpqr Total loading time: 0 Render date: 2024-06-19T14:53:48.345Z Has data issue: false hasContentIssue false
  • English
  • Français

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 beverly.muhlhausler@adelaide.edu.au)
Get access Rights & Permissions [Opens in a new window]

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 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.Pietilainen, KH, Kaprio, J, Rasanen, M, et al. Tracking of body size from birth to late adolescence: contributions of birth length, birth weight, duration of gestation, parents’ body size, and twinship. Am J Epidemiol. 2001; 154, 21–29.CrossRefGoogle ScholarPubMed
2.Parsons, TJ, Power, C, Logan, S, Summerbell, CD. Childhood predictors of adult obesity: a systematic review. Int J Obes Relat Metab Disord. 1999; 23, S1–S107.Google ScholarPubMed
3.Yajnik, CS, Lubree, HG, Rege, SS, et al. Adiposity and hyperinsulinemia in indians are present at birth. J Clin Endocrinol Metab. 2002; 87, 5575–5580.CrossRefGoogle ScholarPubMed
4.Fall, CHD, Osmond, C, Barker, DJP, et al. Fetal and infant growth and cardiovascular risk factors in women. Brit Med J. 1995; 310, 428–432.CrossRefGoogle ScholarPubMed
5.McMillen, IC, Robinson, JS. Developmental origins of the metabolic syndrome: prediction, plasticity, and programming. Physiol Rev. 2005; 85, 571–633.CrossRefGoogle ScholarPubMed
6.Flanagan, DE, Moore, VM, Godsland, IF, et al. Fetal growth and the physiological control of glucose tolerance in adults: a minimal model analysis. Am J Physiol Endocrinol Metab. 2000; 278, E700–E706.CrossRefGoogle ScholarPubMed
7.Ozanne, SE. Metabolic programming in animals: type 2 diabetes. Br Med Bull. 2001; 60, 143–152.CrossRefGoogle Scholar
8.De Blasio, MJ, Gatford, KL, McMillen, IC, Robinson, JS, Owens, JA. Placental restriction of fetal growth increases insulin action, growth and adiposity in the young lamb. Endocrinology. 2006; 148, 1350–1358.CrossRefGoogle ScholarPubMed
9.Malina, RM, Katzmarzyk, PT, Beunen, G. Birth weight and its relationship to size attained and relative fat distribution at 7 to 12 years of age. Obes Res. 1996; 4, 385–390.CrossRefGoogle Scholar
10.Ozanne, SE, Nave, BT, Wang, CL, et al. Poor fetal nutrition causes long-term changes in expression of insulin signaling components in adipocytes. Am J Physiol Endocrinol Metab. 1997; 273, E46–E51.CrossRefGoogle ScholarPubMed
11.Ozanne, SE, Dorling, MW, Wang, CL, Nave, BT. Impaired pi 3-kinase activation in adipocytes from early growth-restricted male rats. Am J Physiol Endocrinol Metab. 2001; 280, E534–E539.CrossRefGoogle ScholarPubMed
12.Muhlhausler, BS, Duffield, JA, Ozanne, SE, et al. The transition from fetal growth restriction to accelerated postnatal growth: a potential role for insulin signalling in skeletal muscle. J Physiol. 2009; 587, 4199–4211.CrossRefGoogle ScholarPubMed
13.Daval, M, Foufelle, F, Ferre, P. Functions of amp-activated protein kinase in adipose tissue. J Physiol. 2006; 574, 55–62.CrossRefGoogle ScholarPubMed
14.Hardie, DG, Hawley, SA, Scott, JW. Amp-activated protein kinase – development of the energy sensor concept. J Physiol (Lond). 2006; 574, 7–15.CrossRefGoogle ScholarPubMed
15.Kersten, S. Mechanisms of nutritional and hormonal regulation of lipogenesis. EMBO Rep. 2001; 21, 282–286.CrossRefGoogle Scholar
16.Laitinen, J, Pietilainen, K, Wadsworth, M, Sovio, U, Jarvelin, MR. Predictors of abdominal obesity among 31-y-old men and women born in northern finland in 1966. Eur J Clin Nutr. 2004; 58, 180–190.CrossRefGoogle ScholarPubMed
17.Duffield, JA, Vuocolo, T, Tellam, R, et al. Intrauterine growth restriction and the sex specific programming of leptin and peroxisome proliferator-activated receptor gamma (ppargamma) mrna expression in visceral fat in the lamb. Pediatr Res. 2009; 66, 59–65.CrossRefGoogle ScholarPubMed
18.Edwards, LJ, Simonetta, G, Owens, JA, Robinson, JS, McMillen, IC. Restriction of placental and fetal growth in sheep alters fetal blood pressure responses to angiotensin ii and captopril. J Physiol. 1999; 515, 897–904.CrossRefGoogle ScholarPubMed
19.Morrison, JL, Botting, KJ, Dyer, JL, et al. Restriction of placental function alters heart development in the sheep fetus. Am J Physiol Regul Integr Comp Physiol. 2007; 293, R306–R313.CrossRefGoogle ScholarPubMed
20.Aldermann, GA, Morgan, DE, Harvard, A, Edwards, RE, Todd, JR. Energy allowances and feeding systems for ruminants. In Ministry of agriculture, fisheries and food: Technical bulletin 33, 1975; pp. 1–79. Her Majesty's Stationery Office: London.Google Scholar
21.Muhlhausler, BS, Roberts, CT, McFarlane, JR, Kauter, KG, McMillen, IC. Fetal leptin is a signal of fat mass independent of maternal nutrition in ewes fed at or above maintenance energy requirements. Biol Reprod. 2002; 67, 493–499.CrossRefGoogle ScholarPubMed
22.Wang, KCW, Zhang, L, McMillen, IC, et al. Fetal growth restriction and the programming of heart growth and cardiac insulin-like growth factor 2 expression in the lamb. J Physiol. 2011; 589, 4709–4722.CrossRefGoogle ScholarPubMed
23.Muhlhausler, BS, Adam, CL, Findlay, PA, Duffield, JA, McMillen, IC. Increased maternal nutrition alters development of the appetite-regulating network in the brain. FASEB J. 2006; 20, 1257–1259.CrossRefGoogle ScholarPubMed
24.Duffield, JA, Vuocolo, T, Tellam, R, et al. Placental restriction of fetal growth decreases igf1 and leptin mrna expression in the perirenal adipose tissue of late gestation fetal sheep. Am J Physiol Regul Integr Comp Physiol. 2008; 294, R1413–R1419.CrossRefGoogle ScholarPubMed
25.Philp, LK, Muhlhausler, BS, Janovska, A, et al. Maternal overnutrition suppresses the phosphorylation of 5′-amp-activated protein kinase in liver, but not skeletal muscle, in the fetal and neonatal sheep. Am J Physiol Regul Integr Comp Physiol. 2008; 295, R1982–R1990.CrossRefGoogle Scholar
26.Forhead, AJ, Lamb, CA, Franko, KL, et al. Role of leptin in the regulation of growth and carbohydrate metabolism in the ovine fetus during late gestation. J Physiol. 2008; 586, 2393–2403.CrossRefGoogle ScholarPubMed
27.Park, SH, Gammon, SR, Knippers, JD, et al. Phosphorylation-activity relationships of ampk and acetyl-coa carboxylase in muscle. J Appl Physiol. 2002; 92, 2475–2482.CrossRefGoogle ScholarPubMed
28.Steinberg, GR, Rush, JWE, Dyck, DJ. Ampk expression and phosphorylation are increased in rodent muscle after chronic leptin treatment. Am J Physiol Endocrinol Metab. 2003; 284, E648–E654.CrossRefGoogle ScholarPubMed
29.Shepherd, PR, Crowther, NJ, Desai, M, Hales, CN, Ozanne, SE. Altered adipocyte properties in the offspring of protein malnourished rats. Br J Nutr. 1997; 78, 121–129.CrossRefGoogle ScholarPubMed
30.Ozanne, S, Wang, C, Dorling, M, Petry, C. Dissection of the metabolic actions of insulin in adipocytes from early growth-retarded male rats. J Endocrinol. 1999; 162, 313–319.CrossRefGoogle ScholarPubMed
31.Viollet, B, Andreelli, F, Jorgensen, SB, et al. The amp-activated protein kinase {alpha}2 catalytic subunit controls whole-body insulin sensitivity. J Clin Invest. 2003; 111, 91–98.CrossRefGoogle Scholar
32.Steinberg, GR, Macaulay, SL, Febbraio, MA, Kemp, BE. Amp-activated protein kinase – the fat controller of the energy railroad. Can J Physiol Pharmacol. 2006; 84, 655–665.CrossRefGoogle ScholarPubMed
33.Jørgensen, SB, Viollet, B, Andreelli, F, et al. Knockout of the α2 but not α1 5′-amp-activated protein kinase isoform abolishes 5-aminoimidazole-4-carboxamide-1-β-4-ribofuranosidebut not contraction-induced glucose uptake in skeletal muscle. J Biol Chem. 2004; 279, 1070–1079.CrossRefGoogle Scholar
34.Gaidhu, MP, Fediuc, S, Ceddia, RB. 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside-induced amp-activated protein kinase phosphorylation inhibits basal and insulin-stimulated glucose uptake, lipid synthesis, and fatty acid oxidation in isolated rat adipocytes. J Biol Chem. 2006; 281, 25956–25964.CrossRefGoogle ScholarPubMed
35.Kramer, HF, Witczak, CA, Fujii, N, et al. Distinct signals regulate as160 phosphorylation in response to insulin, aicar, and contraction in mouse skeletal muscle. Diabetes. 2006; 55, 2067–2076.CrossRefGoogle ScholarPubMed