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

J Biol Chem. 2010 Oct 22;285(43):33028-33036. doi: 10.1074/jbc.M109.089391. Epub 2010 Aug 18.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Circadian Rhythm / physiology*
  • Diet
  • Dietary Carbohydrates / pharmacology
  • Dietary Fats / pharmacology
  • Dietary Proteins / pharmacology
  • Fasting / metabolism
  • Feeding Behavior / drug effects
  • Feeding Behavior / physiology*
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology*
  • Humans
  • Liver / metabolism*
  • Mice
  • Mice, Obese
  • Phosphorylation / drug effects
  • Phosphorylation / physiology
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Sterol Regulatory Element Binding Protein 1 / biosynthesis*
  • Sterol Regulatory Element Binding Protein 1 / genetics


  • Dietary Carbohydrates
  • Dietary Fats
  • Dietary Proteins
  • Srebf1 protein, mouse
  • Sterol Regulatory Element Binding Protein 1
  • Proto-Oncogene Proteins c-akt