Dietary restriction induces a sexually dimorphic type I interferon response in mice with gene-environment interactions

• Published in: Cell reports (Cambridge) Vol. 42; no. 6; p. 112559
• Main Authors: Harney, Dylan J., Cielesh, Michelle, Roberts, Georgia E., Vila, Isabelle K., Viengkhou, Barney, Hofer, Markus J., Laguette, Nadine, Larance, Mark
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 27.06.2023
• Subjects: Animal biology; castration; cholesterol; fatty acid synthesis; Food and Nutrition; Immunology; Innate immunity; interferon α; intermittent fasting; Life Sciences; liver; mass spectrometry; ovariectomy; proteomics; sexual dimorphism; testosterone; Vertebrate Zoology; testosterone; proteomics; liver; MS; castration; CP: Immunology; intermittent fasting; fatty acid synthesis; mass spectrometry; cholesterol; interferon α; sexual dimorphism; ovariectomy
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2023.112559

Intermittent fasting (IF) is an established intervention to treat the growing obesity epidemic. However, the interaction between dietary interventions and sex remains a significant knowledge gap. In this study, we use unbiased proteome analysis to identify diet-sex interactions. We report sexual dimorphism in response to intermittent fasting within lipid and cholesterol metabolism and, unexpectedly, in type I interferon signaling, which was strongly induced in females. We verify that secretion of type I interferon is required for the IF response in females. Gonadectomy differentially alters the every-other-day fasting (EODF) response and demonstrates that sex hormone signaling can either suppress or enhance the interferon response to IF. IF fails to potentiate a stronger innate immune response when IF-treated animals were challenged with a viral mimetic. Lastly, the IF response changes with genotype and environment. These data reveal an interesting interaction between diet, sex, and the innate immune system. [Display omitted] •Intermittent fasting induces sexually dimorphic changes in the mouse liver proteome•Females induce interferon-stimulated genes that require type I interferon secretion•Gonadectomy shows the key role of ongoing sex hormone signaling in this effect•The magnitude of the response changes with genetic background and environment In this study, the effect of intermittent fasting is examined in the liver proteome of mice. Harney et al. observe a sexually dimorphic response in lipid metabolism pathways and type I interferon signaling. This response differs with gonadectomy. The magnitude of this response differs between mouse strains and environments.