Obesity and metabolic syndrome in circadian Clock mutant mice.
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.
Turek
Fred W
FW
Department of Neurology, Northwestern University, Evanston, IL 60208, USA.
Joshu
Corinne
C
Kohsaka
Akira
A
Lin
Emily
E
Ivanova
Ganka
G
McDearmon
Erin
E
Laposky
Aaron
A
Losee-Olson
Sue
S
Easton
Amy
A
Jensen
Dalan R
DR
Eckel
Robert H
RH
Takahashi
Joseph S
JS
Bass
Joseph
J
D017667:Adipocytes / Q000473:pathology; D000818:Animals; D001835:Body Weight; D001921:Brain / Q000378:metabolism; D056926:CLOCK Proteins; D002940:Circadian Rhythm; D004041:Dietary Fats / Q000008:administration & dosage; D002149:Energy Intake; D004734:Energy Metabolism; D005247:Feeding Behavior; D022781:Hepatocytes / Q000473:pathology; D006943:Hyperglycemia; D006949:Hyperlipidemias; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D024821:Metabolic Syndrome / Q000235:genetics / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity; D009154:Mutation; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000235:genetics / Q000503:physiopathology*; D015534:Trans-Activators / Q000235:genetics* / Q000502:physiology*; D015430:Weight Gain
D004041:Dietary Fats; D007328:Insulin; D020738:Leptin; D009479:Neuropeptides; D015534:Trans-Activators; D056926:CLOCK Proteins; C538944:Clock protein, mouse