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Inhibition of IL-1beta improves Glycaemia in a Mouse Model for Gestational Diabetes.

ABSTRACT: Gestational diabetes mellitus (GDM) is one of the most common diseases associated with pregnancy, however, the underlying mechanisms remain unclear. Based on the well documented role of inflammation in type 2 diabetes, the aim was to investigate the role of inflammation in GDM. We established a mouse model for GDM on the basis of its two major risk factors, obesity and aging. In these GDM mice, we observed increased Interleukin-1? (IL-1?) expression in the uterus and the placenta along with elevated circulating IL-1? concentrations compared to normoglycemic pregnant mice. Treatment with an anti-IL-1? antibody improved glucose-tolerance of GDM mice without apparent deleterious effects for the fetus. Finally, IL-1? antagonism showed a tendency for reduced plasma corticosterone concentrations, possibly explaining the metabolic improvement. We conclude that IL-1? is a causal driver of impaired glucose tolerance in GDM.

SUBMITTER: Schulze F

PROVIDER: S-EPMC7033251 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Inhibition of IL-1beta improves Glycaemia in a Mouse Model for Gestational Diabetes.

Schulze Friederike F Wehner Josua J Kratschmar Denise V DV Makshana Valmir V Meier Daniel T DT Häuselmann Stéphanie P SP Dalmas Elise E Thienel Constanze C Dror Erez E Wiedemann Sophia J SJ Traub Shuyang S Nordmann Thierry M TM Rachid Leila L De Baat Axel A Rohm Theresa V TV Zhao Cheng C Odermatt Alex A Böni-Schnetzler Marianne M Donath Marc Y MY

Scientific reports 20200220 1

Gestational diabetes mellitus (GDM) is one of the most common diseases associated with pregnancy, however, the underlying mechanisms remain unclear. Based on the well documented role of inflammation in type 2 diabetes, the aim was to investigate the role of inflammation in GDM. We established a mouse model for GDM on the basis of its two major risk factors, obesity and aging. In these GDM mice, we observed increased Interleukin-1β (IL-1β) expression in the uterus and the placenta along with elev ...[more]

PMID: 32080229

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Project description:Intrahepatic cholestasis of pregnancy (ICP) is characterized by elevated maternal circulating bile acid levels and associated dyslipidemia. ICP leads to accumulation of bile acids in the fetal compartment, and the elevated bile acid concentrations are associated with an increased risk of adverse fetal outcomes. The farnesoid X receptor agonist obeticholic acid (OCA) is efficient in the treatment of cholestatic conditions such as primary biliary cholangitis. We hypothesized that OCA administration during hypercholanemic pregnancy will improve maternal and fetal bile acid and lipid profiles. Female C57BL/6J mice were fed either a normal chow diet, a 0.5% cholic acid (CA)-supplemented diet, a 0.03% OCA-supplemented diet, or a 0.5% CA + 0.03% OCA-supplemented diet for 1 wk before mating and throughout pregnancy until euthanization on day 18. The effects of CA and OCA feeding on maternal and fetal morphometry, bile acid and lipid levels, and cecal microbiota were investigated. OCA administration during gestation did not alter the maternal or fetal body weight or organ morphometry. OCA treatment during hypercholanemic pregnancy reduced bile acid levels in the fetal compartment. However, fetal dyslipidemia was not reversed, and OCA did not impact maternal bile acid levels or dyslipidemia. In conclusion, OCA administration during gestation had no apparent detrimental impact on maternal or fetal morphometry and improved fetal hypercholanemia. Because high serum bile acid concentrations in ICP are associated with increased rates of adverse fetal outcomes, further investigations into the potential use of OCA during cholestatic gestation are warranted.NEW & NOTEWORTHY We used a mouse model of gestational hypercholanemia to investigate the use of obeticholic acid (OCA), a potent FXR agonist, as a treatment for the hypercholanemia of intrahepatic cholestasis of pregnancy (ICP). The results demonstrate that OCA can improve the fetal bile acid profile. This is relevant not only to women with ICP but also for women who become pregnant while receiving OCA treatment for other conditions such as primary biliary cholangitis and nonalcoholic steatohepatitis.

Dataset Information

Inhibition of IL-1beta improves Glycaemia in a Mouse Model for Gestational Diabetes.

Publications

Inhibition of IL-1beta improves Glycaemia in a Mouse Model for Gestational Diabetes.

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