Attenuating effect of clock mutation on triglyceride contents in the ICR mouse liver under a high-fat diet.
Energy homeostasis is subjected to a circadian control that synchronizes energy intake and expenditure. The transcription factor CLOCK, a key component of the molecular circadian clock, controls many kinds of rhythms, such as those for locomotor activity, body temperature, and metabolic functions. The purpose of the present study is to understand the function of the Clock gene during lipid metabolism in the liver using Clock-mutant mice. Clock-mutant mice with an ICR background were fed a high-fat diet for 13 weeks, and liver triglyceride, serum triglyceride, and serum free fatty acid levels were examined. Triglyceride content in the liver was significantly less increased in Clock-mutant mice on a high-fat diet compared to wild-type mice on a high-fat diet. Acsl4 and Fabp1 mRNA levels in the liver showed daily rhythms in wild-type mice. In contrast, Clock -mutant mice had attenuated daily rhythms of Acsl4 and Fabp1 gene expression in the liver under both normal and high-fat diet conditions compared to wild-type mice. In Clock-mutant mice, suppression of Acsl4 and Fabp1 mRNA in the liver under high-fat diet conditions may have attenuated the accumulation of triglycerides in the liver compared to wild-type mice under the same conditions. In conclusion, the authors demonstrate that mice with a Clock mutation showed less triglyceride accumulation in the liver through the suppression of Acsl4 and Fabp1 gene expression when fed a high-fat diet compared to wild-type mice fed the same diet.
Department of Physiology and Pharmacology, School of Science and Engineering, Waseda University, Tokyo, Japan.
Takashi
T
Kudo
Toru
T
Tamagawa
Mihoko
M
Kawashima
Natsuko
N
Mito
Shigenobu
S
Shibata
D000818:Animals; D056926:CLOCK Proteins; D002940:Circadian Rhythm / Q000502:physiology*; D004041:Dietary Fats / Q000008:administration & dosage* / Q000378:metabolism; D005223:Fats / Q000494:pharmacology*; D005227:Fatty Acids / Q000032:analysis / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D013997:Time Factors; D015534:Trans-Activators; D014280:Triglycerides / Q000097:blood*
D004041:Dietary Fats; D005223:Fats; D005227:Fatty Acids; D015534:Trans-Activators; D014280:Triglycerides; D056926:CLOCK Proteins; C538944:Clock protein, mouse