We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Loss of testosterone induces postprandial insulin resistance and increases the expression of the hepatic antioxidant flavin‐containing monooxygenases in mice exposed to intermittent hypoxia.
- Authors
Ganouna‐Cohen, Gauthier; Marcouiller, François; Blachot‐Minassian, Britanny; Demarest, Maud; Beauparlant, Charles Joly; Droit, Arnaud; Belaidi, Elise; Bairam, Aida; Joseph, Vincent
- Abstract
Aim: We tested the hypothesis that low testosterone alters the effects of intermittent hypoxia (IH) on glucose homeostasis, hepatic oxidative stress, and transcriptomic profile in male mice. Methods: We used sham‐operated or orchiectomized (ORX) mice exposed to normoxia (Nx) or IH for 2 weeks. We performed fasting insulin and glucose tolerance tests and assessed fasting and postprandial insulin resistance with the HOMA‐IR. The activity of hepatic prooxidant (NADPH oxidase—NOX), antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase—SOD, Cat, GPx), lipid peroxidation (MDA concentration), and the total concentration of glutathione (GSH) were measured under postprandial conditions. mRNA sequencing and pathway enrichment analyses were used to identify hepatic genes underlying the interactions between IH and testosterone. Results: In Sham mice, IH improves fasting insulin sensitivity and glucose tolerance, while there are no effects of IH in ORX mice. In ORX mice, IH induces postprandial hyperinsulinemia, insulin resistance, and a prooxidant profile of enzyme activity (low SOD activity) without altering hepatic MDA and GSH content. ORX and IH altered the expression of genes involved in oxidoreductase activities, cytochromes‐dependent pathways, and glutathione metabolism. Among the genes upregulated in ORX‐IH mice, the flavin‐containing monooxygenases (FMO) are particularly relevant since these are potent hepatic antioxidants that could help prevent overt oxidative stress in ORX‐IH mice. Conclusion: Low levels of testosterone in male mice exposed to IH induce post‐prandial hyperinsulinemia and insulin resistance and determine the mechanisms by which the liver handles IH‐induced oxidative stress.
- Subjects
INSULIN resistance; CHYLOMICRONS; MONOOXYGENASES; NADPH oxidase; TESTOSTERONE; GLUCOSE tolerance tests
- Publication
Acta Physiologica, 2024, Vol 240, Issue 3, p1
- ISSN
1748-1708
- Publication type
Article
- DOI
10.1111/apha.14089