The role of falling leptin levels in the neuroendocrine and metabolic adaptation to short-term starvation in healthy men

Jean L. Chan, Kathleen Heist, Alex M. DePaoli, Johannes D Veldhuis, Christos S. Mantzoros

Research output: Contribution to journalArticle

423 Citations (Scopus)

Abstract

To elucidate the role of leptin in regulating neuroendocrine and metabolic function during an acute fast, six to eight healthy, lean men were studied under four separate conditions: a baseline fed state and three 72-hour fasting studies with administration of either placebo, low-dose recombinantmethionyl human leptin (r-metHuLeptin), or replacement-dose r-metHuLeptin designed to maintain serum leptin at levels similar to those in the fed state. Replacement-dose r-metHuLeptin administered during fasting prevents the starvation-induced changes in the hypothalamic-pituitary-gonadal axis and, in part, the hypothalamic-pituitary-thyroid axis and IGF-1 binding capacity in serum. Thus, in normal men, the fall in leptin with fasting may be both necessary and sufficient for the physiologic adaptations of these axes, which require leptin levels above a certain threshold for activation. In contrast to findings in mice, fasting-induced changes in the hypothalamic-pituitary-adrenal, renin-aldosterone, and growth hormone-IGF-1 axes as well as fuel utilization may be independent of leptin in humans. The role of leptin in normalizing several starvation-induced neuroendocrine changes may have important implications for the pathophysiology and treatment of eating disorders and obesity.

Original languageEnglish (US)
Pages (from-to)1409-1421
Number of pages13
JournalJournal of Clinical Investigation
Volume111
Issue number9
DOIs
StatePublished - May 2003

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Starvation
Leptin
Fasting
Insulin-Like Growth Factor I
Physiological Adaptation
Aldosterone
Serum
Renin
Growth Hormone
Thyroid Gland
Obesity
Placebos

ASJC Scopus subject areas

  • Medicine(all)

Cite this

The role of falling leptin levels in the neuroendocrine and metabolic adaptation to short-term starvation in healthy men. / Chan, Jean L.; Heist, Kathleen; DePaoli, Alex M.; Veldhuis, Johannes D; Mantzoros, Christos S.

In: Journal of Clinical Investigation, Vol. 111, No. 9, 05.2003, p. 1409-1421.

Research output: Contribution to journalArticle

Chan, Jean L. ; Heist, Kathleen ; DePaoli, Alex M. ; Veldhuis, Johannes D ; Mantzoros, Christos S. / The role of falling leptin levels in the neuroendocrine and metabolic adaptation to short-term starvation in healthy men. In: Journal of Clinical Investigation. 2003 ; Vol. 111, No. 9. pp. 1409-1421.
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