Structure, production and signaling of leptin

Abstract

The cloning of leptin in 1994 was an important milestone in obesity research. In those days obesity was stigmatized as a condition caused by lack of character and self-control. Mutations in either leptin or its receptor were the first single gene mutations found to cause morbid obesity, and it is now appreciated that obesity is caused by a dysregulation of central neuronal circuits. From the first discovery of the leptin deficient obese mouse (ob/ob), to the cloning of leptin (ob aka lep) and leptin receptor (db aka lepr) genes, much has been learned about leptin and its action in the central nervous system. The initial high hopes that leptin would cure obesity were quickly dampened by the discovery that most obese humans have increased leptin levels and develop leptin resistance. Nevertheless, leptin target sites in the brain represent an excellent blueprint for distinct neuronal circuits that control energy homeostasis. A better understanding of the regulation and interconnection of these circuits will further guide and improve the development of safe and effective interventions to treat obesity. This review will highlight our current knowledge about the hormone leptin, its signaling pathways and its central actions to mediate distinct physiological functions.

Serum Leptin and Adiponectin Concentration in Type 2 Diabetes Patients in the Short and Long Term Following Biliopancreatic Diversion

“…Leptin directly enhances the production of cytokines and interleukins, activates monocytes and macrophages to produce pro-inflammatory agents, and stimulates the production of complement and vascular endothelial growth factor in human hepatic cells [29,31]. Leptin suppresses insulin secretion in a negative feedback loop where insulin stimulates the release of leptin: by consequence, the development of a leptin resistance with an excess of leptin availability might lead to a decreased insulin action [34,35]. There can be also a crosstalk between the levels of leptin and adiponectin, and therefore in an uncomplicated obese patient, a negative relationship between serum adiponectin and leptin concentrations has been demonstrated [21,23].…”

Serum cytokine profiles as predictors of asthma control in adults from the EGEA study

“…Determination of serum cytokine levels (at EGEA2) was carried out at the IMIM (Instituto Hospital del Mar de Investigaciones Médicas, Barcelona, Spain) using the Luminex xMAG ® technique in a BioPlex system. Analyses were restricted to IL-1Ra, IL-5, IL-7, IL-8, IL-10, IL-13 and TNF-α because, as expected, around 50% of the measurements of IL-6 were undetectable, and because leptin has multiple roles that are largely beyond inflammation [26]. No value above or below the limit of detection (LD) was observed for IL-7 and IL-13 measurements.…”

Leptin upregulates COX‑2 and its downstream products in aortic endothelial cells

“…Its main function is to target the hypothalamic arcuate nucleus, resulting in the suppression of appetite and increase of energy consumption so as to regulate the energy balance (1).…”