Disrupted fat absorption attenuates obesity induced by a high-fat diet in Clock mutant mice

• Published in: FEBS letters Vol. 580; no. 1; pp. 127 - 130
• Main Authors: Oishi, Katsutaka, Atsumi, Gen-ichi, Sugiyama, Shinobu, Kodomari, Ikuko, Kasamatsu, Manami, Machida, Kazuhiko, Ishida, Norio
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 09-01-2006
• Subjects: Animals; Cholecystokinin - biosynthesis; Cholecystokinin-A receptor; Circadian rhythm; Circadian Rhythm - physiology; Clock; CLOCK Proteins; Dietary Fats - administration & dosage; Dietary Fats - metabolism; Fatty Acids - blood; Gene Expression Regulation - drug effects; Gene Expression Regulation - genetics; Homeostasis - genetics; Lipid digestion; Lipogenesis; Mice; Mice, Mutant Strains; Obesity; Obesity - blood; Obesity - genetics; Receptor, Cholecystokinin A - biosynthesis; Trans-Activators - deficiency; Trans-Activators - metabolism; Triglycerides - blood; Cholecystokinin-A receptor; Obesity; Lipid digestion; Circadian rhythm; Clock; Lipogenesis
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2005.11.063

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.