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Leptin Receptors

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

Abstract

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.

Keywords

Leptin Leptin receptors Obesity 

Abbreviations

AgRP

Agouti-related protein

ARC

Arcuate nucleus of the hypothalamus

CART

Cocaine- and amphetamine-regulated transcript

CNS

Central nervous system

CSF

Cerebrospinal fluid

DIO

Diet-induced obesity

DMH

Dorsal medial nucleus

ERK

Extra-cellular signal-regulated kinase

JAK

Janus kinase

LepR

Leptin receptor

LHA

Lateral hypothalamic area

NPY

Neuropeptide-Y

NTS

Nucleus tractus solitarius

PI3K

Phosphoinositide 3-kinase

POMC

Pro-opiomelanocortin

PVN

Paraventricular nucleus

SH2

Src homology 2

SOCS

Suppressors of cytokine signalling

STAT

Signal transducer and activator of transcription

VMH

Ventromedial nucleus

VTA

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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