Leptin resistance and diet-induced obesity: central and peripheral actions of leptin

Metabolism. 2015 Jan;64(1):35-46. doi: 10.1016/j.metabol.2014.10.015. Epub 2014 Oct 23.


Obesity is a chronic disease that represents one of the most serious global health burdens associated to an excess of body fat resulting from an imbalance between energy intake and expenditure, which is regulated by environmental and genetic interactions. The adipose-derived hormone leptin acts via a specific receptor in the brain to regulate energy balance and body weight, although this protein can also elicit a myriad of actions in peripheral tissues. Obese individuals, rather than be leptin deficient, have in most cases, high levels of circulating leptin. The failure of these high levels to control body weight suggests the presence of a resistance process to the hormone that could be partly responsible of disturbances on body weight regulation. Furthermore, leptin resistance can impair physiological peripheral functions of leptin such as lipid and carbohydrate metabolism and nutrient intestinal utilization. The present document summarizes those findings regarding leptin resistance development and the role of this hormone in the development and maintenance of an obese state. Thus, we focused on the effect of the impaired leptin action on adipose tissue, liver, skeletal muscle and intestinal function and the accompanying relationships with diet-induced obesity. The involvement of some inflammatory mediators implicated in the development of obesity and their roles in leptin resistance development are also discussed.

Keywords: Diet; Inflammation; Leptin resistance; Obesity.

Publication types

  • Review

MeSH terms

  • Animals
  • Body Weight / physiology
  • Central Nervous System / metabolism*
  • Central Nervous System / physiopathology*
  • Diet
  • Humans
  • Leptin / metabolism*
  • Obesity / metabolism*
  • Obesity / physiopathology*
  • Peripheral Nervous System / metabolism*
  • Peripheral Nervous System / physiopathology*


  • Leptin