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PMID: 15845877 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Obesity and metabolic syndrome in circadian Clock mutant mice.

Science (New York, N.Y.) ·Vol. 308 ·No. 5724 ·2005-05-13 ·Pages 1043-5

Turek FW, Joshu C, Kohsaka A, Lin E, Ivanova G, McDearmon E, Laposky A, Losee-Olson S, Easton A, Jensen DR, Eckel RH, Takahashi JS, Bass J

Abstract

The CLOCK transcription factor is a key component of the molecular circadian clock within pacemaker neurons of the hypothalamic suprachiasmatic nucleus. We found that homozygous Clock mutant mice have a greatly attenuated diurnal feeding rhythm, are hyperphagic and obese, and develop a metabolic syndrome of hyperleptinemia, hyperlipidemia, hepatic steatosis, hyperglycemia, and hypoinsulinemia. Expression of transcripts encoding selected hypothalamic peptides associated with energy balance was attenuated in the Clock mutant mice. These results suggest that the circadian clock gene network plays an important role in mammalian energy balance.

MeSH Terms
Adipocytes/pathology Animals Body Weight Brain/metabolism CLOCK Proteins Circadian Rhythm Dietary Fats/administration & dosage Energy Intake Energy Metabolism Feeding Behavior Hepatocytes/pathology Hyperglycemia Hyperlipidemias Insulin/blood Leptin/blood Metabolic Syndrome/genetics,physiopathology Mice Mice, Inbred C57BL Motor Activity Mutation Neuropeptides/genetics,metabolism Obesity/genetics,physiopathology Trans-Activators/genetics,physiology Weight Gain
Chemicals
Dietary Fats Insulin Leptin Neuropeptides Trans-Activators CLOCK Proteins Clock protein, mouse
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Turek Fred W
Department of Neurology, Northwestern University, Evanston, IL 60208, USA.
Joshu Corinne
Kohsaka Akira
Lin Emily
Ivanova Ganka
McDearmon Erin
Laposky Aaron
Losee-Olson Sue
Easton Amy
Jensen Dalan R
Eckel Robert H
Takahashi Joseph S
Bass Joseph
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Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
DOI
10.1126/science.1108750
Published
2005-05-13
Epub
2005-00-21
Pages
1043-5
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC3764501
Subset
IM
Grants
NHLBI NIH HHS · R01 HL075029 · United States
NHLBI NIH HHS · HL59598 · United States
NIDDK NIH HHS · K08 DK002675 · United States
NHLBI NIH HHS · HL75029 · United States
NHLBI NIH HHS · R01 HL059598 · United States
Howard Hughes Medical Institute · United States
NIDDK NIH HHS · DK26356 · United States
NIA NIH HHS · R01 AG018200 · United States
NIDDK NIH HHS · DK02675 · United States
NIDDK NIH HHS · R01 DK026356 · United States
NIA NIH HHS · AG11412 · United States
NIA NIH HHS · AG18200 · United States
NIA NIH HHS · P01 AG011412 · United States
External Links
PubMed source DOI: 10.1126/science.1108750 PMC Full Text View journal details
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