Impairment of Peripheral Circadian Clocks Precedes Metabolic Abnormalities in ob/ob Mice

• DOI: 10.1210/en.2010-1068
• Publication Date: 2011-02-02T03:45:07Z
• Authors: Hitoshi Ando; Masafumi Kumazaki; Yuya Motosugi; Kentarou Ushijima; Tomohiro Maekawa; Eiko Ishikawa; Akio Fujimura
• Keywords: PER1; PER2; Hyperinsulinemia

Abstract Recent studies have demonstrated relationships between the dysfunction of circadian clocks and development metabolic abnormalities, but chicken-and-egg question remains unresolved. To address this issue, we investigated cause-effect relationship in obese, diabetic ob/ob mice. Compared with control C57BL/6J mice, daily mRNA expression profiles clock clock-controlled genes Clock, Bmal1, Cry1, Per1, Per2, Dbp were substantially dampened liver adipose tissue, not hypothalamic suprachiasmatic nucleus, 10-wk-old Four-week feeding a low-calorie diet administration leptin over 7-d period attenuated, to significant comparable extent, observed abnormalities (obesity, hyperglycemia, hyperinsulinemia, hypercholesterolemia) However, only treatment improved impaired peripheral clocks. In addition, function, assessed by measuring levels at around peak times, was also reduced tissues 3-wk-old mice without any overt abnormalities. Collectively these results indicate that impairment does result from may instead be least partially caused deficiency itself. Further are needed clarify how affects