Gestational Diabetes Sensitizes Mice to Future Metabolic Syndrome That Can Be Relieved by Activating CAR.
Endocrinology
; 163(7)2022 07 01.
Article
de En
| MEDLINE
| ID: mdl-35524740
ABSTRACT
Diabetes and related metabolic syndrome are common metabolic disorders. Gestational diabetes mellitus (GDM) is rather prevalent in the clinic. Although most GDM resolves after therapeutic intervention and/or after delivery, the long-term health effect of GDM remains to be better understood. The constitutive androstane receptor (CAR), initially characterized as a xenobiotic receptor, was more recently proposed to be a therapeutic target for obesity and type 2 diabetes mellitus (T2DM). In this study, high-fat diet (HFD) feeding was used to induce GDM. Upon delivery, GDM mice were returned to chow diet until the metabolic parameters were normalized. Parous non-GDM control females or metabolically normalized GDM females were then subjected to HFD feeding to induce nongestational obesity and T2DM. Our results showed that GDM sensitized mice to metabolic abnormalities induced by a second hit of HFD. Treatment with the CAR agonist 1,4-bis [2-(3,5 dichloropyridyloxy)] benzene efficiently attenuated GDM-sensitized and HFD-induced obesity and T2DM, including decreased body weight, improved insulin sensitivity, inhibition of hyperglycemia and hepatic steatosis, increased oxygen consumption, and decreased adipocyte hypertrophy. In conclusion, our results have established GDM as a key risk factor for the future development of metabolic disease. We also propose that CAR is a therapeutic target for the management of metabolic disease sensitized by GDM.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Diabète gestationnel
/
Syndrome métabolique X
/
Diabète de type 2
Type d'étude:
Risk_factors_studies
Limites:
Animals
/
Female
/
Humans
/
Pregnancy
Langue:
En
Journal:
Endocrinology
Année:
2022
Type de document:
Article