Chronic increase of circulating galanin levels induces obesity and marked alterations in lipid metabolism similar to metabolic syndrome

Objective: Galanin ( GAL) has a role in the regulation of food intake by way of acting on the central nervous system in rodents. High serum GAL levels have been observed in obese human subjects, suggesting that peripheral GAL has a role in the regulation of energy balance and that elevated circulating GAL levels contribute to the development of obesity and obesity-associated metabolic impairments. Currently, it is not known how chronically increased levels of circulating GAL affect energy balance. The purpose of this study is to clarify the importance of chronically increased levels of circulating GAL on energy balance in a transgenic mouse model. Research design and methods: Male wild-type and homozygous galanin transgenic (GAL-Tg) mice were used to study the peripheral effects of a 10-fold increase in circulating GAL on food intake, body weight, lipid metabolism, hepatic steatosis, glucose homeostasis and energy expenditure. Results: In the absence of an orexigenic effect, GAL-Tg mice had increased body weight, visceral adiposity, total serum cholesterol, total serum triglycerides and hyperinsulinemia, as well as impaired glucose tolerance. Compared with wild-type mice, the obese phenotype observed in the GAL-Tg mice was attributed to decreased oxygen consumption and carbon dioxide production, and this effect was independent of any changes in food intake or horizontal activity. In this obese model, GAL contributed to the development of fatty liver disease, which was associated with impaired glucose tolerance, as well as a reduction in heat production and metabolic rate. Conclusions: Chronically elevated GAL may regulate body weight, metabolic rate, and lipid and carbohydrate metabolism through a mechanism that is independent of feeding regulation. The obese phenotype in the GAL-Tg mice is related to the reduced energy expenditure and insulin resistance. These findings support the hypothesis that increased circulating GAL levels contribute to the development of metabolic syndrome. International Journal of Obesity ( 2009) 33, 1381-1389; doi: 10.1038/ijo.2009.187; published online 22 September 2009