Apolipoprotein A-I Protects Against Pregnancy-Induced Insulin Resistance in Rats

Objective-Insulin resistance and inflammation in pregnancy are risk factors for gestational diabetes mellitus. Increased plasma HDL (high-density lipoprotein) and apo (apolipoprotein) A-I levels have been reported to improve glucose metabolism and inhibit inflammation in animals and humans. This study asks whether increasing plasma apoA-I levels improves insulin sensitivity and reduces inflammation in insulin-resistant pregnant rats. Approach and Results-Insulin-resistant pregnant rats received intravenous infusions of lipid-free apoA-I (8 mg/kg) or saline on days 6, 9, 12, 15, and 18 of pregnancy. The rats were then subjected to a euglycemic-hyperinsulinemic clamp. Glucose uptake was increased in white and brown adipose tissue by 57 +/- 13% and 32 +/- 10%, respectively (P<0.05 for both), and in quadriceps and gastrocnemius muscle by 35 +/- 9.7% and 47 +/- 14%, respectively (P<0.05 for both), in the apoA-I-treated pregnant rats relative to saline-infused pregnant rats. The pregnant rats that were treated with apoA-I also had reduced plasma TNF-alpha (tumor necrosis factor-a) levels by 57 +/- 8.4%,plasma IL (interleukin)-6 levels by 67 +/- 9.5%, and adipose tissue macrophage content by 54 +/- 8.2% (P<0.05 for all) relative to the saline-treated pregnant rats. Conclusions-These studies establish that apoA-I protects against pregnancy-induced insulin resistance in rats by increasing insulin sensitivity in adipose tissue and skeletal muscle and inhibiting inflammation. This identifies apoA-I as a potential target for preventing pregnancy-induced insulin resistance and reducing the incidence of gestational diabetes mellitus. Visual Overview-An online visual overview is available for this article.