Loss of testosterone induces postprandial insulin resistance and increases the expression of the hepatic antioxidant flavin-containing monooxygenases in mice exposed to intermittent hypoxia.
FMO3
insulin resistance
intermittent hypoxia
liver
monooxygenase
testosterone
Journal
Acta physiologica (Oxford, England)
ISSN: 1748-1716
Titre abrégé: Acta Physiol (Oxf)
Pays: England
ID NLM: 101262545
Informations de publication
Date de publication:
17 Jan 2024
17 Jan 2024
Historique:
revised:
29
11
2023
received:
25
06
2023
accepted:
01
01
2024
medline:
17
1
2024
pubmed:
17
1
2024
entrez:
17
1
2024
Statut:
aheadofprint
Résumé
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. 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. 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. 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.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e14089Subventions
Organisme : CIHR
ID : 162232
Pays : Canada
Informations de copyright
© 2024 The Authors. Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.
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