| First Author | Bienvenu G | Year | 2005 |
| Journal | Diabetologia | Volume | 48 |
| Issue | 6 | Pages | 1189-97 |
| PubMed ID | 15889232 | Mgi Jnum | J:99658 |
| Mgi Id | MGI:3583406 | Doi | 10.1007/s00125-005-1767-6 |
| Citation | Bienvenu G, et al. (2005) Dysregulation of energy homeostasis in mice overexpressing insulin-like growth factor-binding protein 6 in the brain. Diabetologia 48(6):1189-97 |
| abstractText | 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. |
