Leptin Receptors

  • Elizabeth C. Cottrell
  • Julian G. Mercer
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 209)


The hormone leptin, secreted predominantly from adipose tissue, plays a crucial role in the regulation of numerous neuroendocrine functions, from energy homeostasis to reproduction. Genetic deficiency as a consequence of leptin or leptin receptor mutations, although rare in humans, leads to early onset of chronic hyperphagia and massive obesity. In most human obesity, however, leptin levels are chronically elevated. Under these conditions of persistent hyperleptinaemia, and particularly when obesity is associated with a high-fat diet, leptin resistance develops, and signalling through the leptin receptor is curtailed, fuelling further weight gain. Here, we review the role of leptin receptors in the regulation of feeding and obesity development. Leptin receptors are found in each of the major components of the CNS “feeding” circuitry—the brainstem, hypothalamus and distributed reward centres. Through these receptors, leptin exerts influences on signalling and integration within these circuits to alter feeding behaviours. Although some progress is now being made with peptide analogues, the leptin receptor has not proved to be amenable to small molecule pharmacological intervention to date. Where clinical benefit from recombinant leptin administration has been achieved, this has been under circumstances of complete endogenous leptin deficiency or relative hypoleptinaemia such as in lipodystrophy.


Leptin Leptin receptors Obesity 



Agouti-related protein


Arcuate nucleus of the hypothalamus


Cocaine- and amphetamine-regulated transcript


Central nervous system


Cerebrospinal fluid


Diet-induced obesity


Dorsal medial nucleus


Extra-cellular signal-regulated kinase


Janus kinase


Leptin receptor


Lateral hypothalamic area




Nucleus tractus solitarius


Phosphoinositide 3-kinase




Paraventricular nucleus


Src homology 2


Suppressors of cytokine signalling


Signal transducer and activator of transcription


Ventromedial nucleus


Ventral tegmental area


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Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Elizabeth C. Cottrell
    • 1
  • Julian G. Mercer
    • 2
  1. 1.Centre for Cardiovascular Science, Queen’s Medical Research InstituteUniversity of EdinburghEdinburghUK
  2. 2.Division of Obesity and Metabolic Health, Rowett Institute of Nutrition and HealthUniversity of AberdeenAberdeenUK

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