AUTHOR=Pérez-Matute Patricia , López Icíar P. , Íñiguez María , Recio-Fernández Emma , Torrens Raquel , Piñeiro-Hermida Sergio , Alfaro-Arnedo Elvira , Chau Luong , Walz Christina , Hoeflich Andreas , Oteo José A. , Pichel José G. TITLE=IGF1R is a mediator of sex-specific metabolism in mice: Effects of age and high-fat diet JOURNAL=Frontiers in Endocrinology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.1033208 DOI=10.3389/fendo.2022.1033208 ISSN=1664-2392 ABSTRACT=Objective

We aimed to investigate the short and long-term metabolic consequences of IGF1R systemic gene deficiency in mice.

Methods

UBC-CreERT2, Igf1rfl/fl mutant mice were used to suppress IGF1R signaling in adult tissues by inducing postnatal generalized Igf1r deletion with tamoxifen. Animals were analyzed at two different ages: i) 13-weeks old young mice, and ii) 12-months old middle-aged mice. In addition, the effects of 10 weeks-long high-fat diet (HFD) were investigated in middle-aged mice.

Results

Young IGF1R-deficient mice were insulin-resistant, with high IGF1, growth hormone (GH) and IGFBP3, as well as low IGFBP2 circulating levels. Males also presented increased triglycerides in liver. In contrast, middle-aged mice did not clearly show all of these alterations, suggesting possible compensatory effects. Middle-aged IGF1R-deficient male mice were able to counteract the negative effects induced by aging and HFD in adiposity, inflammation and glucose metabolism. A metabolic sexual dimorphism dependent on IGF1R was observed, especially in middle-aged mice.

Conclusions

These results demonstrate that IGF1R is involved in metabolic homeostasis, with effects modulated by diet-induced obesity and aging in a sex dependent manner. Thus, IGF1R deficiency in mice is proposed as a useful tool to understand metabolic alterations observed in patients with IGF1R gene deletions.