title: Loss of circadian rhythm of circulating insulin concentration induced by high-fat diet intake is associated with disrupted rhythmic expression of circadian clock genes in the liver.
abstract: OBJECTIVE
  Peripheral clock genes show a circadian rhythm is correlated with the timing of feeding in peripheral tissues. It was reported that these clock genes are strongly regulated by insulin action and that a high-fat diet (HFD) intake in C57BL/6J mice for 21days induced insulin secretion during the dark phase and reduced the circadian rhythm of clock genes. In this study, we examined the circadian expression patterns of these clock genes in insulin-resistant animal models with excess secretion of insulin during the day.
  
  
  METHODS
  We examined whether insulin resistance induced by a HFD intake for 80days altered blood parameters (glucose and insulin concentrations) and expression of mRNA and proteins encoded by clock and functional genes in the liver using male ICR mice.
  
  
  RESULTS
  Serum insulin concentrations were continuously higher during the day in mice fed a HFD than control mice. Expression of lipogenesis-related genes (Fas and Accβ) and the transcription factor Chrebp peaked at zeitgeber time (ZT)24 in the liver of control mice. A HFD intake reduced the expression of these genes at ZT24 and disrupted the circadian rhythm. Expression of Bmal1 and Clock, transcription factors that compose the core feedback loop, showed circadian variation and were synchronously associated with Fas gene expression in control mice, but not in those fed a HFD.
  
  
  CONCLUSIONS
  These results indicate that the disruption of the circadian rhythm of insulin secretion by HFD intake is closely associated with the disappearance of circadian expression of lipogenic and clock genes in the liver of mice.
authors.affiliation: Laboratory of Nutritional Physiology, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, Shizuoka 422-8526, Japan.
authors.forename: Kazue
authors.initials: K
authors.lastname: Honma
authors.affiliation: Laboratory of Nutritional Physiology, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, Shizuoka 422-8526, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Hikosaka
authors.affiliation: Laboratory of Nutritional Physiology, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, Shizuoka 422-8526, Japan; Laboratory of Food and Nutritional Sciences, Department of Local Produce and Food Sciences, Faculty of Life and Environmental Sciences, University of Yamanashi, Yamanashi 400-8510, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Mochizuki
authors.affiliation: Laboratory of Nutritional Physiology, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, Shizuoka 422-8526, Japan. Electronic address: gouda@u-shizuoka-ken.ac.jp.
authors.forename: Toshinao
authors.initials: T
authors.lastname: Goda
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D057906:Circadian Clocks / Q000187:drug effects* / Q000235:genetics; D056925:Circadian Rhythm Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics*; D059305:Diet, High-Fat; D015870:Gene Expression / Q000187:drug effects; D007328:Insulin / Q000097:blood*; D050155:Lipogenesis / Q000235:genetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009929:Organ Size / Q000187:drug effects; D014157:Transcription Factors / Q000235:genetics
chemical_list: D001786:Blood Glucose; D056925:Circadian Rhythm Signaling Peptides and Proteins; D007328:Insulin; D014157:Transcription Factors
keywords: Circadian rhythm; Clock gene; High-fat diet; Lipid metabolism; Liver