Effect of peripheral circadian dysfunction on metabolic disease in response to a diabetogenic diet.

Research paper by Sonja S SS Pijut, Danielle E DE Corbett, Yuhuan Y Wang, Jianing J Li, Richard J RJ Charnigo, Gregory A GA Graf

Indexed on: 07 Apr '16Published on: 07 Apr '16Published in: American journal of physiology. Endocrinology and metabolism


BMAL1 is a core component of the transcription/translation machinery that regulates central and peripheral circadian rhythms which coordinate behavior and metabolism, respectively. Our objective was to determine the impact of BMAL1 in adipose alone, or in combination with liver, on metabolic phenotypes. Control, adipose-Bmal1 knockout (ABKO) and liver- and adipose-Bmal1 knockout (LABKO) female mice were placed in TSE System metabolic chambers for metabolic phenotyping. A second cohort of male mice was fed a control or diabetogenic diet and body weight and composition, glucose tolerance, insulin sensitivity and serum and hepatic lipids were measured. Both female ABKO and LABKO mice exhibited increased food consumption compared to control mice. ABKO mice also exhibited increased overall activity, predominantly during the light phase, compared to both control and LABKO mice and were protected from increased weight gain. When the male cohort was challenged with a diabetogenic diet, LABKO mice had increased body weight due to increased fat mass compared to control and ABKO mice. However, these mice did not present further impairments in glycemic control, adipose inflammation or liver injury. LABKO mice had increased hepatic cholesterol and elevated expression of cholesterol synthesis and uptake genes. Our data indicate that deletion of this allele in adipose or in combination with liver alters feeding behavior and locomotor activity. However, obesity is exacerbated only with the combination of liver and adipose deletion.