Leptin was initially thought to have a role in energy homeostasis and obesity. More recently, it has also been implicated in the regulation of reproduction, glucose homeostasis, bone formation, wound healing and the immune system. Leptin acts via leptin receptors, which are transmembrane catalytic receptors found on NPY/AgRP and α-MSH/CART neurons in hypothalamic nuclei.
Leptin receptors (Ob-Rs) are coded for by one human gene that produces six different isoforms; Ob-Ra to Ob-Rf. Ob-Rs exist as constitutive dimers at physiological expression levels. Only the Ob-Rb isoform can transduce intracellular signals and does so through activation of the JAK2/STAT3, PI 3-K and MAPK signaling cascades. Activation of Ob-Rs mediates transcriptional regulation of the hypothalamic melanocortin pathway and downregulates endocannabinoid expression.
Leptin resistance has been proposed as a pathophysiological mechanism of obesity. In obese individuals, Ob-Ra (which is involved in active transport of leptin across the blood-brain barrier) expression is downregulated and the individual may be unresponsive to leptin signals. Ob-R antagonists are of great interest in the development of pharmacological treatments for obesity.View all products for Leptin Receptors »
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Literature for Leptin Receptors
Written by Sonia Tucci, Lynsay Kobelis and Tim Kirkham, this review provides a synopsis of the increasing number of peptides that have been implicated in appetite regulation and energy homeostasis; putative roles of the major peptides are outlined and compounds available from Tocris are listed.Download PDF | View all reviews
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