Leptin Mechanism

Leptin is a small protein hormone involved in the control of energy intake, appetite, and metabolism. As a key regulator of food intake and body weight, it is one of the most important cytokines secreted by the adipose tissue.

Mechanism of action

The actions of leptin are exerted when it binds with a leptin receptor. At least six isoforms of this receptor are known including:

• Ob-Ra or LepRa
• Ob-Rb or LepRb
• Ob-Rc or LepRc
• Ob-Rd or LepRd
• Ob-Re or LepRe
• Ob-Rf or LepRf

These receptors are coded for by a single gene called LEPR. Of these six receptors, the longest isoform Ob-Rb is the only one fully capable of performing intracellular signalling and is present in the nuclei of the cells in the hypothalamus. This cell signalling is achieved via the Jak-Stat and MAP Kinase signal transduction pathways.

It is not yet clear whether leptin is able to cross the blood brain-barrier to reach the brain and access is generally thought to be achieved at the choroid plexus where there is an abundance of one form of leptin receptor.

Once bound to the Ob-Rb receptor, the signal transducer stat3 is phosphorylated and moves towards the cell nucleus where it is thought to modify gene expression. One example of this gene modification and therefore the function of leptin is the down-regulation of endocannabinoid receptor expression, which would usually act to increase appetite and therefore food intake.

In animal models, leptin resistance has been showed to suppress food intake and lead to weight loss.