HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Summary Full Text Full Text (PDF) All Versions of this Article: fj.05-5241fjev1 20/8/1257    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Muhlhausler, B. S. Articles by McMillen, I. C. Search for Related Content PubMed PubMed Citation Articles by Muhlhausler, B. S. Articles by McMillen, I. C.

Increased maternal nutrition alters development of the appetite-regulating network in the brain

B. S. Muhlhausler^*, C. L. Adam, P. A. Findlay, J. A. Duffield^* and I. C. McMillen^*,1

^* Research Centre for the Early Origins of Adult Health, School of Molecular and Biomedical Science, University of Adelaide, Adelaide, Australia; and

Obesity and Metabolic Division, Rowett Research Institute, Bucksburn, Aberdeen, Scotland, UK

¹Correspondence: Sansom Research Institute, University of South Australia, SA 5005, Australia. E-mail: caroline.mcmillen{at}unisa.edu.au

ABSTRACT

Individuals exposed to an increased nutrient supply before birth have a high risk of becoming obese children and adults. It has been proposed that exposure of the fetus to high maternal nutrient intake results in permanent changes within the central appetite regulatory network. No studies, however, have investigated the impact of increased maternal nutrition on the appetite regulatory network in species in which this network develops before birth, as in the human. In the present study, pregnant ewes were fed a diet which provided 100% (control, n =8) or 160% (well-fed, n=8) of metabolizable energy requirements. Ewes were allowed to lamb spontaneously, and lambs were sacrificed at 30 days of postnatal age. All fat depots were dissected and weighed, and expression of the appetite-regulating neuropeptides and the leptin receptor (OBRb) were determined by in situ hybridization. Lambs of well-fed ewes had higher glucose (Glc) concentrations during early postnatal life (F=5.93, P<0.01) and a higher relative subcutaneous (s.c.) fat mass at 30 days of age (34.9±4.7 g/kg vs. 22.8±3.3 g/kg; P<0.05). The hypothalamic expression of pro-opiomelanocortin was higher in lambs of well-fed ewes (0.48±0.09 vs. 0.28±0.04, P<0.05). In lambs of overnourished mothers, but not in controls, the expression of OBRb was inversely related to total relative fat mass (r²=0.50, P=0.05, n=8), and the direct relationship between the expression of the central appetite inhibitor CART and fat mass was lost. The expression of neuropeptide Y and AGRP was inversely related to total relative fat mass (NPY, r²=0.28, P<0.05; agouti-related peptide, r²=0.39, P<0.01). These findings suggest that exposure to increased nutrition before birth alters the responses of the central appetite regulatory system to signals of increased adiposity after birth.—Muhlhausler, B. S., Adam, C. L., Findlay, P. A., Duffield, J. A., and McMillen, I. C. Increased maternal nutrition alters development of the appetite-regulating network in the brain.

This article has been cited by other articles:

				L. K. Philp, B. S. Muhlhausler, A. Janovska, G. A. Wittert, J. A. Duffield, and I. C. McMillen 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 Regulatory Integrative Comp Physiol, December 1, 2008; 295(6): R1982 - R1990. [Abstract] [Full Text] [PDF]

				C. L. Adam, P. A. Findlay, A. Chanet, R. P. Aitken, J. S. Milne, and J. M. Wallace Expression of energy balance regulatory genes in the developing ovine fetal hypothalamus at midgestation and the influence of hyperglycemia Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2008; 294(6): R1895 - R1900. [Abstract] [Full Text] [PDF]

				B. S. Muhlhausler, J. A. Duffield, and I. C. McMillen Increased Maternal Nutrition Increases Leptin Expression in Perirenal and Subcutaneous Adipose Tissue in the Postnatal Lamb Endocrinology, December 1, 2007; 148(12): 6157 - 6163. [Abstract] [Full Text] [PDF]

				P. D. Taylor and L. Poston Developmental programming of obesity in mammals Exp Physiol, March 1, 2007; 92(2): 287 - 298. [Abstract] [Full Text] [PDF]

				B. S. Muhlhausler, J. A. Duffield, and I. C. McMillen Increased Maternal Nutrition Stimulates Peroxisome Proliferator Activated Receptor-{gamma}, Adiponectin, and Leptin Messenger Ribonucleic Acid Expression in Adipose Tissue before Birth Endocrinology, February 1, 2007; 148(2): 878 - 885. [Abstract] [Full Text] [PDF]