Contrasting effects of different levels of food intake and adiposity on LH secretion and hypothalamic gene expression in sheep

Z A Archer, S M Rhind, P A Findlay, C E Kyle, L Thomas, M Marie, C L Adam

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Abstract

Body reserves (long-term) and food intake (short-terns) both contribute nutritional feedback to the hypothalamus. Reproductive neuroendocrine output (GnRH/LH) is stimulated by increased food intake and not by high adiposity in sheep, but it is unknown whether appetite-regulating hypothalamic neurons show this differential response. Castrated male sheep (Scottish Blackface) with oestradiol implants were studied in two 4 week experiments. In Experiment 1, sheep were fed to maintain the initial body condition (BC) score of 2.0 +/- 0.00 (lower BC (LBC), n=7) or 2.9 +/- 0.09 (higher BC (HBC), n=9), and liveweight of 43 +/- 1.1 and 59 +/- 1.6 kg respectively. LBC and HBC sheep had similar mean plasma LH concentration, pulse frequency and amplitude, but HBC animals had higher mean plasma concentrations of insulin (P<0.01), leptin (P<0.01) and glucose (P<0.01). Gene expression (measured by in situ hybridisation) in the hypothalamic arcuate nucleus (ARC) was higher in LBC than HBC sheep for neuropeptide Y (NPY; 486% of HBC, P<0.01), agouti-related peptide (AGRP; 467%, P<0.05) and leptin receptor. (OB-Rb; 141%, P<0.05), but lower for cocaine- and amphetamine-regulated transcript (CART; 92%, P<0.05) and similar between groups for pro-opiomelanocortin (POMC). In Experiment 2, sheep with initial mean BC score 2.4 +/- 0.03 and liveweight 55 +/- 0.8 kg were fed a liveweight-maintenance ration (low intake, LI, n=7) while sheep with initial mean BC score 2.0 +/- 0.03 and liveweight 43 +/- 1.4 kg were fed freely so that BC score increased to 2.5 +/- 0.00 and liveweight increased to 54 +/- 1.4 kg (high intake, HI, n=9). Compared with LI, HI sheep had higher mean plasma LH (P<0.05), baseline LH (P<0.01) and pulse amplitude (P<0.01) and showed a trend towards higher pulse frequency. Although there were no differences in final mean plasma concentrations, there were significant increases over time in mean concentrations of insulin (P<0.001), leptin (P<0.05) and glucose (P<0.001) in HI sheep. Gene expression for AGRP in the ARC was higher in HI than LI animals (453% of LI; P<0.05), but expression levels were similar for NPY, OB-Rb, CART and POMC. Thus, the hypothalamus shows differential responses to steady-state adiposity as opposed to an increase in food intake, in terms of both reproductive neuroendocrine activity and hypothalamic appetite-regulating pathways. Differences in hypothalamic gene expression were largely consistent with contemporary levels of systemic leptin and insulin feedback; however, increased nutritional feedback was stimulatory to GnRH/LH whereas constant high feedback was not. The hypothalamus therefore has the ability to retain a nutritional memory that can influence subsequent responses.

Original languageEnglish
Pages (from-to)383-393
Number of pages11
JournalJournal of Endocrinology
Volume175
Issue number2
DOIs
Publication statusPublished - 2002

Keywords

  • adipose tissue
  • animals
  • autoradiography
  • blood glucose
  • body weight
  • eating
  • fatty acids, nonesterified
  • gene expression
  • hypothalamus
  • insulin
  • leptin
  • luteinizing hormone
  • male
  • orchiectomy
  • sheep
  • pulsatile luteinizing-hormone
  • amphetamine-regulated transcript
  • gonadotropin-releasing hormone
  • melanin-concentrating-hormone
  • agouti-related-protein
  • mature male sheep
  • neuropeptide-Y
  • body condition
  • ovariectomized ewes
  • growth-hormone

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