Frontiers in Endocrinology (Oct 2022)

IGF1R is a mediator of sex-specific metabolism in mice: Effects of age and high-fat diet

  • Patricia Pérez-Matute,
  • Icíar P. López,
  • María Íñiguez,
  • Emma Recio-Fernández,
  • Raquel Torrens,
  • Sergio Piñeiro-Hermida,
  • Elvira Alfaro-Arnedo,
  • Luong Chau,
  • Christina Walz,
  • Andreas Hoeflich,
  • José A. Oteo,
  • José G. Pichel,
  • José G. Pichel

DOI
https://doi.org/10.3389/fendo.2022.1033208
Journal volume & issue
Vol. 13

Abstract

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ObjectiveWe aimed to investigate the short and long-term metabolic consequences of IGF1R systemic gene deficiency in mice.MethodsUBC-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.ResultsYoung 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.ConclusionsThese 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.

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