Obesity and leptin resistance: distinguishing cause from effect.
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.
Myers
Martin G
MG
Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA. mgmyers@umich.edu
Leibel
Rudolph L
RL
Seeley
Randy J
RJ
Schwartz
Michael W
MW
D000818:Animals; D030801:Animals, Genetically Modified; D004195:Disease Models, Animal; D004351:Drug Resistance / Q000235:genetics / Q000502:physiology*; D006801:Humans; D020738:Leptin / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D008954:Models, Biological; D009765:Obesity / Q000150:complications* / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D054411:Receptors, Leptin / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
D020738:Leptin; D054411:Receptors, Leptin