| First Author | Pérez-Matute P | Year | 2022 |
| Journal | Front Endocrinol (Lausanne) | Volume | 13 |
| Pages | 1033208 | PubMed ID | 36353242 |
| Mgi Jnum | J:330962 | Mgi Id | MGI:7383548 |
| Doi | 10.3389/fendo.2022.1033208 | Citation | Perez-Matute P, et al. (2022) IGF1R is a mediator of sex-specific metabolism in mice: Effects of age and high-fat diet. Front Endocrinol (Lausanne) 13:1033208 |
| abstractText | Objective: We aimed to investigate the short and long-term metabolic consequences of IGF1R systemic gene deficiency in mice. Methods: <i>UBC-CreERT2, Igf1r<sup>fl/fl</sup></i> mutant mice were used to suppress IGF1R signaling in adult tissues by inducing postnatal generalized <i>Igf1r</i> deletion with tamoxifen. Animals were analyzed at two different ages: <i>i</i>) 13-weeks old young mice, and <i>ii</i>) 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. |
