Dysregulation of energy homeostasis in mice overexpressing insulin-like growth factor-binding protein 6 in the brain-
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G. Bienvenu, D. Seurin, Y. Le Bouc, P. Even, S. Babajko et al.

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


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)

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