Minireview: A hypothalamic role in energy balance with special emphasis on leptin.

Abstract:

:The hypothalamus is a major site for integration of central and peripheral signals that regulate energy homeostasis. Within the hypothalamus, neurons residing in the ARC (arcuate nucleus)-PVN (paraventricular)-PF/LH (perifornical/lateral hypothalamus) axis communicate among each other and are subjected to the influence of several peripheral factors, including leptin and insulin. Proper signaling in the hypothalamus by leptin, a long-sought peripheral factor that relays the status of fat stores, is critical to normal regulation of food intake and body weight. Leptin action in the hypothalamus is mediated by a large number of orexigenic and anorectic peptide-producing neurons of the ARC-PVN-PF/LH axis. Not only the classical JAK2 (Janus kinase 2)-STAT3 (signal transducer and activator of transcription 3) pathway, but also the phosphatidylinositol-3 kinase-phosphodiesterase 3B-cAMP pathway mediates hypothalamic leptin receptor signaling. It appears that hypothalamic leptin resistance, possibly due to defective nutritional regulation of leptin receptor expression and/or reduced STAT3 signaling in the hypothalamus, contributes to the development of obesity associated with high-fat feeding and aging. Interestingly, hypothalamic neurons may develop leptin resistance despite an intact JAK2-STAT3 signaling path. The role of suppressor of cytokine signaling 3 and other negative regulators of leptin signaling in central leptin resistance needs to be established, an important area of future investigation. Further understanding of the neural circuitry and leptin signaling in the hypothalamus is critical not only for the advancement of our knowledge on the hypothalamic role in energy balance but also for future development of drugs for the attenuation or treatment of obesity and related disorders in humans.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Sahu A

doi

10.1210/en.2004-0032

subject

Has Abstract

pub_date

2004-06-01 00:00:00

pages

2613-20

issue

6

eissn

0013-7227

issn

1945-7170

pii

en.2004-0032

journal_volume

145

pub_type

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