FRI002 IGF-1R Targeting As A Strategy For Reducing Obesity And Improving Metabolism

Disclosure: S. Al-Samerria: None. S. Farooq: None. N. Nandankar: None. A.L. Negron: None. S. Radovick: None. There has been a significant increase in the prevalence of obesity over the past four decades, and it is projected that by 2030, the majority of the global population will fall into the overweight or obese categories if this trend continues. In a previous study, we reported that the ablation of the IGF-1R in GHRH neurons and somatotrophs (S-GIGFRKO) resulted in a sustained decrease in weight gain velocity due to increased lipolysis and higher energy expenditure, despite no changes in caloric intake. To evaluate the effects of a high-fat diet (HFD) on this metabolic phenotype, we challenged S-GIGFRKO mice with a 60% HFD beginning at 4 weeks of age. The S-GIGFRKO mice on the HFD showed normal linear growth, but after 8 weeks on the HFD, both males and females exhibited a sustained decrease in weight gain velocity compared to control mice on the HFD. Metabolic analysis revealed that the male and female S-GIGFRKO mice had higher oxygen consumption, lower carbon dioxide production, reduced body fat mass, increased energy expenditure, and improved glucose tolerance compared to the control mice on the HFD. No differences in food intake or total activity were observed between the two groups. These results demonstrate the important role of the GHRH-GH axis in regulating energy expenditure and fat metabolism, despite an environmental challenge induced by a HFD. Presentation: Friday, June 16, 2023