PMON53 Resistance to weight gain and obesity in mice lacking the IGF-1 receptor in GHRH neurons

Abstract

Abstract IGF-1 signaling plays a pivotal role in regulating GH production through a negative feedback mechanism at the level of the hypothalamus and pituitary. We created a transgenic mouse model with ablation of the IGF-1R in GHRH-neurons (GIGFRKO) that exhibited normal linear growth, however, when fed a normal chow diet, began to have a sustained decrease in weight gain velocity. This was associated with greater energy expenditure and a lower body fat mass, with no change in caloric intake. The aim of the current study was to determine whether this metabolic phenotype would be sustained with a high fat diet challenge. At 4 weeks of age, the mice were placed on a 45% fat diet for 16 weeks. The GIGFRKO mouse model fed a HFD had normal linear growth, but at 10 weeks of age, both male and female mice began to have a sustained decrease in weight gain velocity compared to their age and sex-matched controls. The metabolic assessment demonstrated that the GIGFRKO transgenic mice had higher O2 consumption, lower CO2 production, a reduction in body fat mass, an elevation in energy expenditure, and improved glucose tolerance compared to the control mice on HFD. This was not associated with changes in food intake or activity and was present in males and females. In conclusion, the GIGFRKO transgenic mice are resistant to diet-induced obesity due to the critical role of the GHRH-GH axis in controlling energy expenditure and fat metabolism. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.