Title
The suprachiasmatic nucleus controls circadian energy metabolism and hepatic insulin sensitivity
Author
Coomans, C.P.
van den Berg, S.A.
Lucassen, E.A.
Houben, T.
Pronk, A.C.
van der Spek, R.D.
Kalsbeek, A.
Biermasz, N.R.
Willems van Dijk, K.
Romijn, J.A.
Meijer, J.H.
Publication year
2013
Abstract
Disturbances in the circadian system are associated with the development of type 2 diabetes mellitus. Here, we studied the direct contribution of the suprachiasmatic nucleus (SCN), the central pacemaker in the circadian system, in the development of insulin resistance. Exclusive bilateral SCN lesions in male C57Bl/6J mice, as verified by immunochemistry, showed a small but significant increase in body weight (+17%), which was accounted for by an increase in fat mass. In contrast, mice with collateral damage to the ventromedial hypothalamus and paraventricular nucleus showed severe obesity and insulin resistance. Mice with exclusive SCN ablation revealed a loss of circadian rhythm in activity, oxygen consumption, and food intake. Hyperinsulinemic-euglycemic clamp analysis 8 weeks after lesioning showed that the glucose infusion rate was significantly lower in SCN lesioned mice compared with sham-operated mice (-63%). Although insulin potently inhibited endogenous glucose production (-84%), this was greatly reduced in SCN lesioned mice (-7%), indicating severe hepatic insulin resistance. Our data show that SCN malfunctioning plays an important role in the disturbance of energy balance and suggest that an absence of central clock activity, in a genetically intact animal, may lead to the development of insulin resistance.
Subject
Health
Food and Nutrition
Healthy Living
Life
MHR - Metabolic Health Research
EELS - Earth, Environmental and Life Sciences
To reference this document use:
http://resolver.tudelft.nl/uuid:3bc66720-3617-45c5-9ef3-c4e4c756d19d
DOI
https://doi.org/10.2337/db12-0507
TNO identifier
525801
Source
Diabetes, 62 (62), 1102-1108
Document type
article