title: Rhythmic messenger ribonucleic acid expression of clock genes and adipocytokines in mouse visceral adipose tissue.
abstract: Various peripheral tissues show circadian rhythmicity, which is generated at the cellular level by their own core oscillators that are composed of transcriptional/translational feedback loops involving a set of clock genes. Although the circulating levels of some adipocytokines, i.e. bioactive substances secreted by adipocytes, are on a 24-h rhythmic cycle, it remains to be elucidated whether the clock gene system works in adipose tissue. To address this issue, we investigated the daily mRNA expression profiles of the clock genes and adipocytokines in mouse perigonadal adipose tissues. In C57BL/6J mice, all transcript levels of the clock genes (Bmal1, Per1, Per2, Cry1, Cry2, and Dbp) and adipocytokines (adiponectin, resistin, and visfatin) clearly showed 24-h rhythms. On the other hand, the rhythmic expression of these genes was mildly attenuated in obese KK mice and greatly attenuated in more obese, diabetic KK-A(y) mice. Obese diabetes also diminished the rhythmic expression of the clock genes in the liver. Interestingly, a 2-wk treatment of KK and KK-A(y) mice with pioglitazone impaired the 24-h rhythmicity of the mRNA expression of the clock genes and adipocytokines despite the antidiabetic effect of the drug. In contrast, pioglitazone improved the attenuated rhythmicity in the liver. These findings suggest that the intracellular clock gene system acts in visceral adipose tissues as well as liver and is influenced by the conditions of obesity/type 2 diabetes and pioglitazone treatment.
authors.affiliation: Division of Clinical Pharmacology, Department of Pharmacology, Jichi Medical School, Tochigi, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ando
authors.forename: Hayato
authors.initials: H
authors.lastname: Yanagihara
authors.forename: Yohei
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Yuri
authors.initials: Y
authors.lastname: Obi
authors.forename: Shuichi
authors.initials: S
authors.lastname: Tsuruoka
authors.forename: Toshinari
authors.initials: T
authors.lastname: Takamura
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kaneko
authors.forename: Akio
authors.initials: A
authors.lastname: Fujimura
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001683:Biological Clocks / Q000235:genetics*; D002940:Circadian Rhythm; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D010507:Periodicity; D000077205:Pioglitazone; D012333:RNA, Messenger / Q000378:metabolism*; D045162:Thiazolidinediones / Q000494:pharmacology; D014781:Viscera
chemical_list: D016207:Cytokines; D007004:Hypoglycemic Agents; D012333:RNA, Messenger; D045162:Thiazolidinediones; D000077205:Pioglitazone