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Ablation of the ID2 gene results in altered circadian feeding behavior, and sex-specific enhancement of insulin sensitivity and elevated glucose uptake in skeletal muscle and brown adipose tissue.

Mathew, D, Zhou, P, Pywell, CM, van der Veen, DR, Shao, J, Xi, Y, Bonar, NA, Hummel, AD, Chapman, S, Leevy, WM and Duffield, GE (2013) Ablation of the ID2 gene results in altered circadian feeding behavior, and sex-specific enhancement of insulin sensitivity and elevated glucose uptake in skeletal muscle and brown adipose tissue. PLoS One, 8 (9).

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Abstract

Inhibitor of DNA binding 2 (ID2) is a helix-loop-helix transcriptional repressor rhythmically expressed in many adult tissues. Our earlier studies have demonstrated a role for ID2 in the input pathway, core clock function and output pathways of the mouse circadian system. We have also reported that Id2 null (Id2-/-) mice are lean with low gonadal white adipose tissue deposits and lower lipid content in the liver. These results coincided with altered or disrupted circadian expression profiles of liver genes including those involved in lipid metabolism. In the present phenotypic study we intended to decipher, on a sex-specific basis, the role of ID2 in glucose metabolism and in the circadian regulation of activity, important components of energy balance. We find that Id2-/- mice exhibited altered daily and circadian rhythms of feeding and locomotor activity; activity profiles extended further into the late night/dark phase of the 24-hr cycle, despite mice showing reduced total locomotor activity. Also, male Id2-/- mice consumed a greater amount of food relative to body mass, and displayed less weight gain. Id2-/- females had smaller adipocytes, suggesting sexual-dimorphic programing of adipogenesis. We observed increased glucose tolerance and insulin sensitivity in male Id2-/- mice, which was exacerbated in older animals. FDG-PET analysis revealed increased glucose uptake by skeletal muscle and brown adipose tissue of male Id2-/- mice, suggesting increased glucose metabolism and thermogenesis in these tissues. Reductions in intramuscular triacylglycerol and diacylglycerol were detected in male Id2-/- mice, highlighting its possible mechanistic role in enhanced insulin sensitivity in these mice. Our findings indicate a role for ID2 as a regulator of glucose and lipid metabolism, and in the circadian control of feeding/locomotor behavior; and contribute to the understanding of the development of obesity and diabetes, particularly in shift work personnel among whom incidence of such metabolic disorders is elevated.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > Surrey Clinical Research Centre
Authors :
AuthorsEmailORCID
Mathew, DUNSPECIFIEDUNSPECIFIED
Zhou, PUNSPECIFIEDUNSPECIFIED
Pywell, CMUNSPECIFIEDUNSPECIFIED
van der Veen, DRUNSPECIFIEDUNSPECIFIED
Shao, JUNSPECIFIEDUNSPECIFIED
Xi, YUNSPECIFIEDUNSPECIFIED
Bonar, NAUNSPECIFIEDUNSPECIFIED
Hummel, ADUNSPECIFIEDUNSPECIFIED
Chapman, SUNSPECIFIEDUNSPECIFIED
Leevy, WMUNSPECIFIEDUNSPECIFIED
Duffield, GEUNSPECIFIEDUNSPECIFIED
Date : 2013
Identification Number : 10.1371/journal.pone.0073064
Related URLs :
Additional Information : Copyright 2013 Mathew et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Depositing User : Symplectic Elements
Date Deposited : 20 Sep 2013 14:00
Last Modified : 09 Jun 2014 13:39
URI: http://epubs.surrey.ac.uk/id/eprint/802291

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