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Circadian Dysfunction Induces Leptin Resistance in Mice.

Authors :
Kettner, Nicole M.
Mayo, Sara A.
Hua, Jack
Lee, Choogon
Moore, David D.
Fu, Loning
Source :
Cell Metabolism; Sep2015, Vol. 22 Issue 3, p448-459, 12p
Publication Year :
2015

Abstract

Summary Circadian disruption is associated with obesity, implicating the central clock in body weight control. Our comprehensive screen of wild-type and three circadian mutant mouse models, with or without chronic jet lag, shows that distinct genetic and physiologic interventions differentially disrupt overall energy homeostasis and Leptin signaling. We found that BMAL1/CLOCK generates circadian rhythm of C/EBPα-mediated leptin transcription in adipose. Per and Cry mutant mice show similar disruption of peripheral clock and deregulation of leptin in fat, but opposite body weight and composition phenotypes that correlate with their distinct patterns of POMC neuron deregulation in the arcuate nucleus. Chronic jet lag is sufficient to disrupt the endogenous adipose clock and also induce central Leptin resistance in wild-type mice. Thus, coupling of the central and peripheral clocks controls Leptin endocrine feedback homeostasis. We propose that Leptin resistance, a hallmark of obesity in humans, plays a key role in circadian dysfunction-induced obesity and metabolic syndromes. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
15504131
Volume :
22
Issue :
3
Database :
Supplemental Index
Journal :
Cell Metabolism
Publication Type :
Academic Journal
Accession number :
109159639
Full Text :
https://doi.org/10.1016/j.cmet.2015.06.005