Dysregulation of energy homeostasis in mice overexpressing insulin-like growth factor-binding protein 6 in the brain-

Authors
G. Bienvenu, D. Seurin, Y. Le Bouc, P. Even, S. Babajko et al.


Lab
National Institute of Health and Medical Research (INSERM) Unit 515, St-Antoine Hospital, Paris, France ; National Institute of Agronomical Research (INRA), Integrated Research Unit (UMR) 914, Paris, France ; National Council for Scientific Research (CNRS

Journal
Diabetologia

Abstract
Aims/hypothesis: IGFs, IGF receptors and IGF binding proteins (IGFBPs) are widely expressed in the central nervous system. To investigate the physiological significance of IGFBP-6 in the brain we established two transgenic mouse lines overexpressing human (h)-IGFBP-6 under the control of glial fibrillary acidic protein promoter. Increasing evidence suggests that insulin/IGF signalling pathways could be implicated in the neuroendocrine regulation of energy homeostasis. We explored the impact of brain IGFBP-6 overexpression on the regulation of food intake and energy balance.  Methods: Transgenic mice were fed either a control diet or a high-fat diet for up to 3 months. Glucose and insulin tolerance tests were carried out before and after the diet period. Plasma parameters (insulin, leptin, glucose, NEFAs and triglycerides) were measured, and uncoupling protein 1 (UCP-1) expression was quantified in brown adipose tissue. Oxygen consumption was also measured in both groups. Results: The transgenic mice fed a high-fat diet for 3 months developed obesity, showing increases in plasma leptin, glucose and insulin levels and mild insulin resistance. As compared with wild-type mice, no significant differences were found in the quantity of food intake. However, UCP-1 expression was down-regulated in the brown adipose tissue of the transgenic mice. Conclusions/interpretation: Our results show that brain IGFBP-6 has an impact on the regulation of energy homeostasis. These transgenic h-IGFBP-6 mice may be considered a new tool for studies of the involvement of the brain IGF system in metabolism control and obesity.

BIOSEB Instruments Used:
OXYLET, Indirect Calorimeter (OXYLET)

Publication request

Thank you for your interest in our product range and your request for this publication, which will be sent to you if the research team and the journal allow it. Our commercial team will contact you as soon as possible.