Selective insulin and leptin resistance in metabolic disorders

Cell Metab. 2012 Aug 8;16(2):144-52. doi: 10.1016/j.cmet.2012.07.004.


Obesity represents a major risk factor for the development of insulin and leptin resistance, ultimately leading to a pleiotropic spectrum of metabolic alterations. However, resistance to both hormones does not uniformly affect all target cells and intracellular signaling pathways. In contrast, numerous clinical phenotypes arise from selective hormone resistance, leading to inhibition of defined intracellular signaling pathways in some tissues, while in other cell types hormone action is maintained or even overactivated. Here, we review the molecular mechanisms and clinical outcomes resulting from selective insulin and leptin resistance, which should ultimately guide future strategies for the treatment of obesity-associated diseases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Central Nervous System / physiopathology*
  • Humans
  • Insulin Resistance / physiology*
  • Leptin / metabolism
  • Leptin / physiology*
  • Metabolic Diseases / etiology
  • Metabolic Diseases / physiopathology*
  • Obesity / complications
  • Obesity / metabolism*
  • Signal Transduction / physiology*


  • Leptin