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

B. S. Muhlhausler, Clare Lesley Adam, P.A. Findlay, J. A. Duffield, I. C. McMillen

Research output: Contribution to journalArticle

163 Citations (Scopus)

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 similar to 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 proopiomelanocortin was higher in lambs of well-fed ewes (0.48 +/- 0.09 vs. 0.28 +/- 0.04, P < 0.05). In lambs of over-nourished mothers, but not in controls, the expression of OBRb was inversely related to total relative fat mass (r(2)=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, r(2)=0.28, P < 0.05; agouti-related peptide, r(2)=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.

Original languageEnglish
Pages (from-to)1257-1259
Number of pages3
JournalThe FASEB Journal
Volume20
Issue number8
DOIs
Publication statusPublished - Jun 2006

Keywords

  • nutrition
  • programming
  • energy balance
  • obesity
  • HYPOTHALAMIC GENE-EXPRESSION
  • POSTNATALLY OVERFED RATS
  • NEUROPEPTIDE-Y-SYSTEM
  • BROWN ADIPOSE-TISSUE
  • LEPTIN RECEPTOR
  • MESSENGER-RNA
  • BIRTH-WEIGHT
  • SHEEP FETUS
  • IN-UTERO
  • NEURONS

Cite this

Increased maternal nutrition alters development of the appetite-regulating network in the brain. / Muhlhausler, B. S.; Adam, Clare Lesley; Findlay, P.A. ; Duffield, J. A.; McMillen, I. C.

In: The FASEB Journal, Vol. 20, No. 8, 06.2006, p. 1257-1259.

Research output: Contribution to journalArticle

Muhlhausler, B. S. ; Adam, Clare Lesley ; Findlay, P.A. ; Duffield, J. A. ; McMillen, I. C. / Increased maternal nutrition alters development of the appetite-regulating network in the brain. In: The FASEB Journal. 2006 ; Vol. 20, No. 8. pp. 1257-1259.
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AU - Adam, Clare Lesley

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N2 - 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 similar to 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 proopiomelanocortin was higher in lambs of well-fed ewes (0.48 +/- 0.09 vs. 0.28 +/- 0.04, P < 0.05). In lambs of over-nourished mothers, but not in controls, the expression of OBRb was inversely related to total relative fat mass (r(2)=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, r(2)=0.28, P < 0.05; agouti-related peptide, r(2)=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.

AB - 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 similar to 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 proopiomelanocortin was higher in lambs of well-fed ewes (0.48 +/- 0.09 vs. 0.28 +/- 0.04, P < 0.05). In lambs of over-nourished mothers, but not in controls, the expression of OBRb was inversely related to total relative fat mass (r(2)=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, r(2)=0.28, P < 0.05; agouti-related peptide, r(2)=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.

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KW - programming

KW - energy balance

KW - obesity

KW - HYPOTHALAMIC GENE-EXPRESSION

KW - POSTNATALLY OVERFED RATS

KW - NEUROPEPTIDE-Y-SYSTEM

KW - BROWN ADIPOSE-TISSUE

KW - LEPTIN RECEPTOR

KW - MESSENGER-RNA

KW - BIRTH-WEIGHT

KW - SHEEP FETUS

KW - IN-UTERO

KW - NEURONS

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DO - 10.1096/fj.05-5241fje

M3 - Article

VL - 20

SP - 1257

EP - 1259

JO - The FASEB Journal

JF - The FASEB Journal

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