Time of day and nutrients in feeding govern daily expression rhythms of the gene for sterol regulatory element-binding protein (SREBP)-1 in the mouse liver.
Sterol regulatory element-binding protein-1 (SREBP-1) plays a central role in transcriptional regulation of genes for hepatic lipid synthesis that utilizes diet-derived nutrients such as carbohydrates and amino acids, and expression of SREBP-1 exhibits daily rhythms with a peak in the nocturnal feeding period under standard housing conditions of mice. Here, we report that the Srebp-1 expression rhythm shows time cue-independent and Clock mutation-sensitive circadian nature, and is synchronized with varied photoperiods apparently through entrainment of locomotor activity and food intake. Fasting caused diminution of Srebp-1 expression, while diabetic db/db and ob/ob mice showed constantly high expression with loss of rhythmicity. Time-restricted feedings during mid-light and mid-dark periods exhibited differential effects, the latter causing more severe damping of the oscillation. Therefore, "when to eat in a day (the light/dark cycle)," rather than "whenever to eat in a day," is a critical determinant to shape the daily rhythm of Srebp-1 expression. We further found that a high-carbohydrate diet and a high-protein diet, as well as a high-fat diet, cause phase shifts of the oscillation peak into the light period, underlining the importance of "what to eat." Daily rhythms of SREBP-1 protein levels and Akt phosphorylation levels also exhibited nutrient-responsive changes. Taken together, these findings provide a model for mechanisms by which time of day and nutrients in feeding shape daily rhythms of the Srebp-1 expression and possibly a number of other physiological functions with interindividual and interdaily differences in human beings and wild animals subjected to day-by-day changes in dietary timing and nutrients.
Matsumoto
Eriko
E
From the Department of Biochemistry and Genetics, Chiba University Graduate School of Medicine, Inohana 1-8-1, Chiba 260-8670.
Ishihara
Akinori
A
From the Department of Biochemistry and Genetics, Chiba University Graduate School of Medicine, Inohana 1-8-1, Chiba 260-8670.
Tamai
Saki
S
From the Department of Biochemistry and Genetics, Chiba University Graduate School of Medicine, Inohana 1-8-1, Chiba 260-8670.
Nemoto
Ayako
A
From the Department of Biochemistry and Genetics, Chiba University Graduate School of Medicine, Inohana 1-8-1, Chiba 260-8670.
Iwase
Katsuro
K
From the Department of Biochemistry and Genetics, Chiba University Graduate School of Medicine, Inohana 1-8-1, Chiba 260-8670.
Hiwasa
Takaki
T
From the Department of Biochemistry and Genetics, Chiba University Graduate School of Medicine, Inohana 1-8-1, Chiba 260-8670.
Shibata
Shigenobu
S
Department of Pharmacology, School of Science and Engineering, Waseda University, Wakamatsu-cho 2-2, Shinjuku-ku 162-8480, Japan.
Takiguchi
Masaki
M
From the Department of Biochemistry and Genetics, Chiba University Graduate School of Medicine, Inohana 1-8-1, Chiba 260-8670. Electronic address: mtak@faculty.chiba-u.jp.
D000818:Animals; D002940:Circadian Rhythm / Q000502:physiology*; D004032:Diet; D004040:Dietary Carbohydrates / Q000494:pharmacology; D004041:Dietary Fats / Q000494:pharmacology; D004044:Dietary Proteins / Q000494:pharmacology; D005215:Fasting / Q000378:metabolism; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008820:Mice, Obese; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000096:biosynthesis* / Q000235:genetics
D004040:Dietary Carbohydrates; D004041:Dietary Fats; D004044:Dietary Proteins; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D051057:Proto-Oncogene Proteins c-akt