Format

Send to

Choose Destination
See comment in PubMed Commons below
Am J Physiol Endocrinol Metab. 2009 Dec;297(6):E1247-59. doi: 10.1152/ajpendo.00274.2009. Epub 2009 Sep 1.

Recent advances in understanding leptin signaling and leptin resistance.

Author information

1
Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Mchigan 48109-0622, USA.

Abstract

The brain controls energy homeostasis and body weight by integrating various metabolic signals. Leptin, an adipose-derived hormone, conveys critical information about peripheral energy storage and availability to the brain. Leptin decreases body weight by both suppressing appetite and promoting energy expenditure. Leptin directly targets hypothalamic neurons, including AgRP and POMC neurons. These leptin-responsive neurons widely connect to other neurons in the brain, forming a sophisticated neurocircuitry that controls energy intake and expenditure. The anorexigenic actions of leptin are mediated by LEPRb, the long form of the leptin receptor, in the hypothalamus. LEPRb activates both JAK2-dependent and -independent pathways, including the STAT3, PI 3-kinase, MAPK, AMPK, and mTOR pathways. These pathways act coordinately to form a network that fully mediates leptin response. LEPRb signaling is regulated by both positive (e.g., SH2B1) and negative (e.g., SOCS3 and PTP1B) regulators and by endoplasmic reticulum stress. Leptin resistance, a primary risk factor for obesity, likely results from impairment in leptin transport, LEPRb signaling, and/or the neurocircuitry of energy balance.

PMID:
19724019
PMCID:
PMC2793049
DOI:
10.1152/ajpendo.00274.2009
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Atypon Icon for PubMed Central
    Loading ...
    Support Center