Obesity and leptin resistance: distinguishing cause from effect

Trends Endocrinol Metab. 2010 Nov;21(11):643-51. doi: 10.1016/j.tem.2010.08.002. Epub 2010 Sep 16.


Because leptin reduces food intake and body weight, the coexistence of elevated leptin levels with obesity is widely interpreted as evidence of 'leptin resistance.' Indeed, obesity promotes a number of cellular processes that attenuate leptin signaling (referred to here as 'cellular leptin resistance') and amplify the extent of weight gain induced by genetic and environmental factors. As commonly used, however, the term 'leptin resistance' embraces a range of phenomena that are distinct in underlying mechanisms and pathophysiological implications. Moreover, the induction of cellular leptin resistance by obesity complicates efforts to distinguish the mechanisms that predispose to weight gain from those that result from it. We suggest a framework for approaching these issues and important avenues for future investigation.

Publication types

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

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Disease Models, Animal
  • Drug Resistance / genetics
  • Drug Resistance / physiology*
  • Humans
  • Leptin / genetics
  • Leptin / metabolism*
  • Leptin / physiology*
  • Models, Biological
  • Obesity / complications*
  • Obesity / etiology*
  • Obesity / genetics
  • Obesity / metabolism
  • Receptors, Leptin / metabolism
  • Receptors, Leptin / physiology
  • Signal Transduction / genetics
  • Signal Transduction / physiology


  • Leptin
  • Receptors, Leptin