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- Title
Glutaredoxin 1 controls monocyte reprogramming during nutrient stress and protects mice against obesity and atherosclerosis in a sex-specific manner.
- Authors
Ahn, Yong Joo; Wang, Luxi; Tavakoli, Sina; Nguyen, Huynh Nga; Short, John D.; Asmis, Reto
- Abstract
High-calorie diet-induced nutrient stress promotes thiol oxidative stress and the reprogramming of blood monocytes, giving rise to dysregulated, obesogenic, proatherogenic monocyte-derived macrophages. We report that in chow-fed, reproductively senescent female mice but not in age-matched male mice, deficiency in the thiol transferase glutaredoxin 1 (Grx1) promotes dysregulated macrophage phenotypes as well as rapid weight gain and atherogenesis. Grx1 deficiency derepresses distinct expression patterns of reactive oxygen species and reactive nitrogen species generators in male versus female macrophages, poising female but not male macrophages for increased peroxynitrate production. Hematopoietic Grx1 deficiency recapitulates this sexual dimorphism in high-calorie diet-fed LDLR-/- mice, whereas macrophage-restricted overexpression of Grx1 eliminates the sex differences unmasked by high-calorie diet-feeding and protects both males and females against atherogenesis. We conclude that loss of monocytic Grx1 activity disrupts the immunometabolic balance in mice and derepresses sexually dimorphic oxidative stress responses in macrophages. This mechanism may contribute to the sex differences reported in cardiovascular disease and obesity in humans. High-calorie diet promotes thiol oxidative stress and the reprogramming of blood monocytes, giving rise to obesogenic and proatherogenic macrophages. Here the authors report that loss of monocytic thiol transferase glutaredoxin 1 results in the derepression of sex-specific oxidative stress responses in macrophages, promoting atherogenesis and obesity in female mice.
- Subjects
GLUTAREDOXIN; HIGH-calorie diet; MONOCYTES; SEXUAL dimorphism; WESTERN diet; WEIGHT gain; REACTIVE nitrogen species; REACTIVE oxygen species
- Publication
Nature Communications, 2022, Vol 13, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-022-28433-2