Obeticholic acid ameliorates dyslipidemia but not glucose tolerance in a mouse model of gestational diabetes.

Obeticholic acid ameliorates dyslipidemia but not glucose tolerance in a mouse model of gestational diabetes. Am J Physiol Endocrinol Metab. 2019 Jun 25;: Authors: McIlvride S, Nikolova V, Fan HM, McDonald JAK, Wahlström A, Bellafante E, Jansen E, Adorini L, Shapiro D, Jones P, Marchesi JR, Marschall HU, Williamson C Abstract Metabolism alters markedly with advancing gestation, characterized by progressive insulin resistance, dyslipidemia, and raised serum bile acids. The nuclear receptor FXR has an integral role in bile acid homeostasis and modulates glucose and lipid metabolism. FXR is known to be functionally suppressed in pregnancy. The FXR agonist, obeticholic acid (OCA) improves insulin sensitivity in type 2 diabetic patients with non-alcoholic fatty liver disease. We therefore hypothesized that OCA treatment during pregnancy could improve disease severity in a mouse model of gestational diabetes mellitus (GDM). C57BL/6J mice were fed a high fat diet (HFD; 60% kcal from fat) for 4 weeks prior to and throughout pregnancy to induce GDM. The impact of the diet supplemented with 0.03% OCA throughout pregnancy was studied. Pregnant HFD-fed mice displayed insulin resistance and dyslipidemia. OCA significantly reduced plasma cholesterol concentrations in non-pregnant and pregnant HFD-fed mice (by 22.4%, p
Source: American Journal of Physiology. Endocrinology and Metabolism - Category: Physiology Authors: Tags: Am J Physiol Endocrinol Metab Source Type: research

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