1646-P: Apolipoprotein A4 Improves Glucose Homeostasis through Activation of BAT Thermogenesis in Obese Mice

Obesity is associated with impaired insulin sensitivity and the development of type 2 diabetes. Activation of brown adipose tissue (BAT) thermogenesis enhances triglyceride clearance and insulin sensitivity. Apolipoprotein A4 (ApoA4) induced by dietary lipids elevates BAT thermogenesis in lean mice. Chronic consumption of high-fat diet (HFD) attenuates APOA4 production in small intestine and BAT thermogenesis. The hypothesis of this study was that the continuous infusion of mouse ApoA4 protein would increase BAT thermogenesis and improve glucose homeostasis in HFD-induced obese mice. Male mice were maintained on an HFD (60% kcals fat) for 10 weeks, during the last 4 weeks, mice received a pump infusion of vehicle or ApoA4 at a physiological dose (1.2 mg ApoA4/kg body weight). Glucose tolerance test, BAT thermogenesis, lipid accumulation in liver, and body weight were measured in mice with ApoA4 or vehicle treatment. Serum glucose and plasma insulin in ApoA4-treated mice was lower than in saline-treated mice following a glucose challenge. BAT temperature and thermogenesis were elevated in ApoA4-treated mice compared to saline-treated mice. Further, ApoA4-treated mice had increased fatty acid oxidation, reduced lipid content, and attenuated steatosis in the liver and decreased body weight gain relative to the saline control mice.

In conclusion, maintenance of ApoA4 protein elevates BAT thermogenesis, reduces body weight gain and hepatic lipid accumulation, and improves glucose homeostasis in HFD-induced obesity.