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Physiology of leptin

Christos Mantzoros, MD, DSc
Section Editor
F Xavier Pi-Sunyer, MD, MPH
Deputy Editor
Kathryn A Martin, MD


Leptin is a product of the ob gene, which is expressed primarily in adipocytes. Leptin acts on leptin receptors (LEPRs), which are widely distributed and account for its pleiotropic effects on energy homeostasis and neuroendocrine, reproductive, and immune function [1]. Leptin is produced primarily in fat cells but also in other organs such as the placenta [2].

The physiology of leptin [3,4] and a review of disorders associated with leptin deficiency are reviewed here. The pathogenesis of obesity and lipodystrophy are reviewed separately. (See "Genetic contribution and pathophysiology of obesity" and "Lipodystrophic syndromes".)


In humans, the leptin gene is located on chromosome 7q32 and consists of three exons and two introns that span 20 kilobases (kb) of DNA. The mouse and human ob genes have 84 percent homology. The gene codes for a secreted protein of 167 amino acids. Leptin is a member of the cytokine family, and its receptor (LEPR) has similarities to the gp130 group of cytokine receptors.

There are at least six isoforms of LEPR (LEPR-a to -f) [5], and all the isoforms are encoded by LEPR gene. The short isoform of the receptor, which is present in several tissues, serves to transport leptin into the brain. There is also a circulating form of the LEPR (LEPR-e) that binds leptin, functions as a leptin-binding protein, and may modulate its action [6].

The LEPR-b receptor is the "longest form," and in most of the cases, mutations in this isoform cause severe obesity. This form of the receptor is located in several organs but, most importantly, areas of the brain, including hypothalamic and other brainstem nuclei. A number of pathogenic mutations have been reported in both the LEP and LEPR [7], which can lead to obesity. LEPR-b is also expressed in cells of the immune system and regulates immune function, most importantly, Type 1/Type 2 T helper (Th1/Th2) cells balance. It is also expressed in the hypothalamic-pituitary-gonadal axis, where it contributes to the regulation of reproductive function.

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Literature review current through: Sep 2017. | This topic last updated: May 09, 2017.
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