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Review
. 2017 Feb 21:8:30.
doi: 10.3389/fendo.2017.00030. eCollection 2017.

The Leptin Receptor Complex: Heavier Than Expected?

Joris Wauman  1 , Lennart Zabeau  1 , Jan Tavernier  1
Affiliations
Review

The Leptin Receptor Complex: Heavier Than Expected?

Joris Wauman et al. Front Endocrinol (Lausanne). .

Abstract

Under normal physiological conditions, leptin and the leptin receptor (ObR) regulate the body weight by balancing food intake and energy expenditure. However, this adipocyte-derived hormone also directs peripheral processes, including immunity, reproduction, and bone metabolism. Leptin, therefore, can act as a metabolic switch connecting the body's nutritional status to high energy consuming processes. We provide an extensive overview of current structural insights on the leptin-ObR interface and ObR activation, coupling to signaling pathways and their negative regulation, and leptin functioning under normal and pathophysiological conditions (obesity, autoimmunity, cancer, … ). We also discuss possible cross-talk with other receptor systems on the receptor (extracellular) and signaling cascade (intracellular) levels.

Keywords: activation; cross-talk; leptin; leptin receptor; leptin resistance; signaling.

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Figures

Figure 1
Figure 1
The activated leptin:ObR complex. Leptin clusters two pre-formed ObR dimers to form an activated 2:4 leptin:ObR complex. In this model, the ObR’s are colored green and red, leptin molecules cyan. The hormone binds with its binding site II to the CRH2 domain of the receptor, while site III residues interact with the immunoglobulin-like domain (IGD) of a second receptor. These residues are colored yellow and green, and defined in the cyan panel. Receptor residues involved in these interactions are shown in the red and green panels. For reasons of clarity, only the CRH2 and IGD domains of each receptor are shown.
Figure 2
Figure 2
Signaling pathways of leptin and its downstream effectors. ObR oligomerization (here only dimerization shown for reasons of clarity) results in phosphorylation and activation of cytoplasmic associated JAK2 kinases. These activated JAKs phosphorylate tyrosine residues in the cytoplasmic tail of the receptor. Recruitment and activation of secondary signaling molecules allow ObR signaling via the JAK/STAT, MAPK, PI3K, AMPK, and mTOR pathways. See text for more details.
See this image and copyright information in PMC

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