Disrupted fat absorption attenuates obesity induced by a high-fat diet in Clock mutant mice.
The Clock gene is a core component of the circadian clock in mammals. We show here that serum levels of triglyceride and free fatty acid were significantly lower in circadian Clock mutant ICR than in wild-type control mice, whereas total cholesterol and glucose levels did not differ. Moreover, an increase in body weight induced by a high-fat diet was attenuated in homozygous Clock mutant mice. We also found that dietary fat absorption was extremely impaired in Clock mutant mice. Circadian expressions of cholecystokinin-A (CCK-A) receptor and lipase mRNAs were damped in the pancreas of Clock mutant mice. We therefore showed that a Clock mutation attenuates obesity induced by a high-fat diet in mice with an ICR background through impaired dietary fat absorption. Our results suggest that circadian clock molecules play an important role in lipid homeostasis in mammals.
Oishi
Katsutaka
K
Clock Cell Biology Research Group, Institute for Biological Resources and Functions, National Institute of Advanced Industrial Science and Technology, Central 6, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan.
Atsumi
Gen-Ichi
G
Sugiyama
Shinobu
S
Kodomari
Ikuko
I
Kasamatsu
Manami
M
Machida
Kazuhiko
K
Ishida
Norio
N
D000818:Animals; D056926:CLOCK Proteins; D002766:Cholecystokinin / Q000096:biosynthesis; D002940:Circadian Rhythm / Q000502:physiology*; D004041:Dietary Fats / Q000008:administration & dosage* / Q000378:metabolism; D005227:Fatty Acids / Q000097:blood*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006706:Homeostasis / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D009765:Obesity / Q000097:blood* / Q000235:genetics; D043886:Receptor, Cholecystokinin A / Q000096:biosynthesis; D015534:Trans-Activators / Q000172:deficiency / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood*
D004041:Dietary Fats; D005227:Fatty Acids; D043886:Receptor, Cholecystokinin A; D015534:Trans-Activators; D014280:Triglycerides; D002766:Cholecystokinin; D056926:CLOCK Proteins; C538944:Clock protein, mouse