Papel del péptido insulinotrópico dependiente de glucosa en la programación nutricional del síndrome metabólico

Abstract

Early nutritional restriction has been associated with increased incidence of metabolic syndrome-associated pathologies in adulthood. However, the underlying mechanisms that determine the development of these diseases are not yet fully known. In the present work, we explored the relevance of glucose-dependent insulinotropic polypeptide (GIP) in the development of these pathologies in a model of Wistar rats. Two groups of dams were fed ad libitum (C) or food-restricted (U) during pregnancy and suckling. At that time, rats were refed a high-fat diet (HFD; CHF and UHF) for 22 weeks. Both male and female UHF rats showed an obese phenotype characterized by hyperphagia, visceral fat accumulation and adipocyte hypertrophy, which was more pronounced than in CHF rats. Oral glucose tolerance tests showed that female UHF rats experienced glucose intolerance, insulin hypersecretion and an exacerbated GIP secretion. Administration of the GIP receptor antagonist, (Pro3)GIP, to UHF female rats markedly reduced visceral fat mass and adipocyte hypertrophy, and these changes were accompanied by improvement of glucose tolerance and insulin sensitivity. In conclusion, the exacerbated production and secretion of GIP seems to represent the stimulus for insulin hypersecretion and insulin resistance shown by UHF female rats, suggesting that GIP may play a critical role in the development of metabolic disturbances related to nutritional rehabilitation.