Programming of hypothalamic neuropeptide gene expression in rats by maternal dietary protein content during pregnancy and lactation

Roselle L. Cripps, Malgorzata S. Martin-Gronert, Zoe A. Archer, C. Nick Hales, Julian Mercer, Susan E. Ozanne

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Epidemiological studies show a link between low birthweight and increased obesity. In contrast, slow growth during the lactation period reduces obesity risk. The present study investigates the potential underlying mechanisms of these observations. Rats were established as follows: (i) control animals [offspring of control dams fed a 20% (w/v) protein diet], (ii) recuperated animals [offspring of dams fed an isocaloric low-protein (8%, w/v) diet during pregnancy and nursed by control dams], and (iii) postnatal low protein animals (offspring of control dams nursed by low-protein-fed dams). Serum and brains were collected from fed and fasted animals at weaning. Expression of hypothalamic energy balance genes was assessed using in situ hybridization. Recuperated pups were smaller at birth, but caught up with controls by day 21 and gained more weight than controls between weaning and 12 weeks of age (P < 0.05). At 21 days, they were hypoleptinaemic compared with controls in the fed state, with generally comparable hypothalamic gene expression. Postnatal low protein offspring had significantly lower body weights than controls at weaning and 12 weeks of age (P < 0.001). At 21 days, they were hypoglycaemic, hypoinsulinaemic and hypoleptinaemic. Leptin receptor gene expression in the arcuate nucleus was increased in postnatal low protein animals compared with controls. Consistent with hypoleptinaemia, hypothalamic gene expression for the orexigenic neuropeptides NPY (neuropeptide Y) and AgRP (Agouti-related peptide) was increased, and that for the anorexigenic neuropeptides POMC (pro-opiomelanocortin) and CART (cocaine- and amphetamine-regulated transcript) was decreased. These results suggest that the early nutritional environment can affect the development of energy balance circuits and consequently obesity risk.

Original languageEnglish
Pages (from-to)85-93
Number of pages9
JournalClinical Science
Volume117
Issue number1-2
DOIs
Publication statusPublished - Jul 2009

Keywords

  • developmental programming
  • energy balance
  • hypothalamic neuropeptide
  • lactation
  • obesity
  • pregnancy
  • POSTNATAL LEPTIN SURGE
  • OVERFED WEANLING RATS
  • CHILDHOOD OBESITY
  • SIBERIAN HAMSTERS
  • ENERGY-BALANCE
  • MESSENGER-RNA
  • NUCLEUS
  • NEURONS
  • GROWTH
  • EXPOSURE

Cite this

Programming of hypothalamic neuropeptide gene expression in rats by maternal dietary protein content during pregnancy and lactation. / Cripps, Roselle L.; Martin-Gronert, Malgorzata S.; Archer, Zoe A.; Hales, C. Nick; Mercer, Julian; Ozanne, Susan E.

In: Clinical Science, Vol. 117, No. 1-2, 07.2009, p. 85-93.

Research output: Contribution to journalArticle

Cripps, Roselle L. ; Martin-Gronert, Malgorzata S. ; Archer, Zoe A. ; Hales, C. Nick ; Mercer, Julian ; Ozanne, Susan E. / Programming of hypothalamic neuropeptide gene expression in rats by maternal dietary protein content during pregnancy and lactation. In: Clinical Science. 2009 ; Vol. 117, No. 1-2. pp. 85-93.
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AB - Epidemiological studies show a link between low birthweight and increased obesity. In contrast, slow growth during the lactation period reduces obesity risk. The present study investigates the potential underlying mechanisms of these observations. Rats were established as follows: (i) control animals [offspring of control dams fed a 20% (w/v) protein diet], (ii) recuperated animals [offspring of dams fed an isocaloric low-protein (8%, w/v) diet during pregnancy and nursed by control dams], and (iii) postnatal low protein animals (offspring of control dams nursed by low-protein-fed dams). Serum and brains were collected from fed and fasted animals at weaning. Expression of hypothalamic energy balance genes was assessed using in situ hybridization. Recuperated pups were smaller at birth, but caught up with controls by day 21 and gained more weight than controls between weaning and 12 weeks of age (P < 0.05). At 21 days, they were hypoleptinaemic compared with controls in the fed state, with generally comparable hypothalamic gene expression. Postnatal low protein offspring had significantly lower body weights than controls at weaning and 12 weeks of age (P < 0.001). At 21 days, they were hypoglycaemic, hypoinsulinaemic and hypoleptinaemic. Leptin receptor gene expression in the arcuate nucleus was increased in postnatal low protein animals compared with controls. Consistent with hypoleptinaemia, hypothalamic gene expression for the orexigenic neuropeptides NPY (neuropeptide Y) and AgRP (Agouti-related peptide) was increased, and that for the anorexigenic neuropeptides POMC (pro-opiomelanocortin) and CART (cocaine- and amphetamine-regulated transcript) was decreased. These results suggest that the early nutritional environment can affect the development of energy balance circuits and consequently obesity risk.

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