20 years of leptin: role of leptin in energy homeostasis in humans

J Endocrinol. 2014 Oct;223(1):T83-96. doi: 10.1530/JOE-14-0358. Epub 2014 Jul 25.

Abstract

The hyperphagia, low sympathetic nervous system tone, and decreased circulating concentrations of bioactive thyroid hormones that are common to states of congenital leptin deficiency and hypoleptinemia following and during weight loss suggest that the major physiological function of leptin is to signal states of negative energy balance and decreased energy stores. In weight-reduced humans, these phenotypes together with pronounced hypometabolism and increased parasympathetic nervous system tone create the optimal circumstance for weight regain. Based on the weight loss induced by leptin administration in states of leptin deficiency (obese) and observed similarity of phenotypes in states of congenital and dietary-induced states of hypoleptinemia (reduced obese), it has been suggested that exogenous leptin could potentially be useful in initiating, promoting, and sustaining weight reduction. However, the responses of human beings to exogenous leptin administration are dependent not only on extant energy stores but also on energy balance. Leptin administration to humans at usual weight has little, if any, effect on body weight while leptin administration during weight loss mitigates hunger, especially if given in supraphysiological doses during severe caloric restriction. Leptin repletion is most effective following weight loss by dietary restriction. In this state of weight stability but reduced energy stores, leptin at least partially reverses many of the metabolic, autonomic, neuroendocrine, and behavioral adaptations that favor weight regain. The major physiological function of leptin is to signal states of negative energy balance and decreased energy stores. Leptin, and pharmacotherapies affecting leptin signaling pathways, is likely to be most useful in sustaining weight loss.

Keywords: energy; leptin; metabolism; obesity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Body Weight / drug effects
  • Body Weight / physiology
  • Energy Metabolism / drug effects
  • Energy Metabolism / physiology*
  • Homeostasis / drug effects
  • Homeostasis / physiology*
  • Humans
  • Leptin / blood
  • Leptin / physiology*
  • Leptin / therapeutic use
  • Models, Biological
  • Obesity / blood
  • Obesity / drug therapy
  • Obesity / physiopathology*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology

Substances

  • Leptin