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This version published online on August 16, 2007
Endocrinology, doi:10.1210/en.2007-0534
A more recent version of this article appeared on November 1, 2007
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*Nutrition

Submitted on April 24, 2007
Accepted on August 9, 2007

Nutritional Influences on Reproductive Neuroendocrine Output: Insulin, Leptin and Orexigenic Neuropeptide Signaling in the Ovine Hypothalamus

David W. Miller, Joanne L. Harrison, Ellen J. Bennett, Patricia A. Findlay, and Clare L. Adam*

Obesity & Metabolic Health Division (J.L.H., E.J.B., P.A.F., C.L.A.), Rowett Research Institute, Aberdeen Centre for Energy Regulation & Obesity, Aberdeen AB21 9SB, Scotland, UK; Sustainable Livestock Systems Group (D.W.M., E.J.B.), Scottish Agricultural College, Aberdeen AB21 9YA, UK; and Integrative Physiology Group, School of Biological Sciences (J.L.H.), University of Aberdeen, Aberdeen AB24 2TZ, UK

* To whom correspondence should be addressed. E-mail: cla{at}rowett.ac.uk.

This study investigated how changing nutritional status may alter reproductive neuroendocrine (LH) output via circulating leptin and insulin signaling through orexigenic hypothalamic pathways. Thin sheep were given an increasing nutritional plane (INP), sheep with intermediate adiposity a static nutritional plane (SNP) and fat sheep a decreasing nutritional plane (DNP) for 6 weeks. Mean group adiposities converged by week 6, LH output increased in INP, remained unchanged in SNP and decreased in DNP sheep. Plasma and cerebrospinal fluid (CSF) insulin and plasma leptin concentrations increased in INP but did not change in SNP and DNP groups. In INP sheep, LH output correlated positively with adiposity and plasma and CSF insulin concentrations and negatively with orexigenic neuropeptide Y (NPY) gene expression in the hypothalamic arcuate nucleus (ARC). In DNP sheep, LH output correlated positively with adiposity, CSF leptin concentrations and ARC pro-opiomelanocortin gene expression, and negatively with leptin receptor (OB-Rb) and agouti-related peptide gene expression in the ARC. These data are consistent with the feedback response to an increasing nutritional plane being mediated by increasing circulating insulin entering the brain and stimulating LH via inhibition of hypothalamic NPY, and the response to a decreasing nutritional plane being mediated by altered hypothalamic leptin signalling brought about by increased OB-Rb expression and decreased melanocortin signalling. Since endpoint adiposity was similar, yet LH output was different, the hypothalamus apparently retains a ‘nutritional memory’, based on changes in orexigenic neuropeptide expression, that influences contemporary neuroendocrine responses.







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