Abstract 398: LDL Receptor Signaling Mediates the Triglyceride-lowering Action of Akkermansia Muciniphila in Genetic Induced Hyperlipidemia

Akkermansia muciniphila (A. muciniphila) is a mucin-degrading bacterium that resides in the mucus layer whose abundance inversely correlates with body weight and the development of diabetes in mice and humans. The objective of this study was to explore the regulatory effect of A. muciniphila on host lipoprotein metabolism, insulin sensitivity and hepatic metabolic inflammation. By establishing a novel mouse model that colonized the A. muciniphila in the gastrointestinal(GI) tract of the cAMP-responsive binding protein H (CREBH)-deficient mouse and in vivo chylomicron assay, we found that increased colonization of A. muciniphila in the GI tract of wild-type mice protected mice from an acute fat load-induced hyperlipidemia compared to vehicle-treated mice. A. muciniphila administration also significantly ameliorated chronic hypertriglyceridemia, improved insulin sensitivity and prevented overproduction of postprandial chylomicrons in the CREBH-null mice. Mechanistic studies revealed that increased A. mucini...