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

• Published in: Diabetologia Vol. 48; no. 6; pp. 1189 - 1197
• Main Authors: BIENVENU, G, SEURIN, D, LE BOUC, Y, EVEN, P, BABAJKO, S, MAGNAN, C
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.06.2005; Springer Nature B.V
• Subjects: Adipose Tissue, Brown - metabolism; Animals; Biological and medical sciences; Blood Glucose - metabolism; Body fat; Brain - drug effects; Brain - physiology; Brain research; Carrier Proteins - metabolism; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Energy; Energy Intake; Energy Metabolism; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fatty Acids, Nonesterified - blood; Food; Glucose; Glucose - pharmacology; Homeostasis; Humans; Hypothalamus; Insulin - blood; Insulin resistance; Insulin-Like Growth Factor Binding Protein 6 - genetics; Insulin-like growth factors; Ion Channels; Leptin - blood; Medical sciences; Membrane Proteins - metabolism; Metabolic diseases; Metabolism; Mice; Mice, Transgenic; Mitochondrial Proteins; Nervous system; Obesity; Oxygen Consumption - drug effects; Physiology; Plasma; Proteins; Transgenic animals; Triglycerides - blood; Uncoupling Protein 1; France; Endocrinopathy; Obesity; Uncoupling protein; Diabetes mellitus; Rodentia; Nutrition disorder; Central nervous system; Homeostasis; Insulin-like growth factors; Encephalon; Insulin like growth factor binding protein; Uncoupling proteins; Vertebrata; Insulin like growth factor; Mammalia; Mouse; Animal; Insulin resistance; Insulin-like growth factor-binding proteins; Nutritional status
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-005-1767-6

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. 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. 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. 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.