Mechanism of Triglyceride Lowering Action of Akkermansia muciniphila and Fenugreek in a Genetic Induced Hyperlipidemia

Hyperlipidemia is a condition of abnormally elevated levels of lipids and/or lipoproteins in the blood circulation. It is usually accompanied with obesity, type 2 diabetes, insulin resistance, hypertension and non-alcoholic fatty liver diseases (NAFLD) and has become a great threat to human health. New therapeutic strategies are needed for the prevention and treatment of both genetic intervention-induced hyperlipidemia and environmentally induced hyperlipidemia. In this study, we determined the therapeutic effects of a disease-protecting gut bacteria, Akkermansia muciniphila, and an annual legume, fenugreek, on hypertriglyceridemia induced by genetic depletion of cAMP responsive binding protein H (CREBH KO) in mice. We found that inoculation of A. muciniphila ameliorates both acute and chronic hyperlipidemia in mice. Increased colonization of A. muciniphila in CREBH KO mice enhanced the expression of hepatic LDL receptor and facilitated the clearance of triglyceride (TG) rich lipoproteins. Moreover, A. muciniphila administration in mice also alleviated hepatic endoplasmic reticulum (ER) stress and metabolic inflammation. Feeding CREBH KO mice with a diet containing fenugreek seed (2%) also attenuated the hypertriglyceridemia caused by depletion of CREBH or induced by a high fat diet (HFD). Fenugreek seed inhibited hepatic apoB100 biosynthesis and suppressed very low density lipoprotein (VLDL) assembly and secretion. It further improved insulin resistance induced by HFD. Acknowledgements The two-year study in UNL is a really valuable and unique experience in my life. I gained strict and great training on doing research and learnt a lot from both my experiments and classes. I would first like to thank my supervisor, Dr. Qiaozhu Su, for all the opportunities, guidance and support she provided to me during my graduate study. I am very grateful that she gave me the opportunity to study at the University of Nebraska-Lincoln, taught me a lot on how to conduct medical research, and has to put up with all the mistakes that I had made during the completion of my research project. I would also like to thank my committee members, Dr. Timothy Carr and Dr. Regis Moreau for their guidance and advice in and out of their classes throughout my studies. Next, I would like to thank the lab members for their help. Xuedong Tong, he taught me the experimental skills when I started my study in 2014. We worked together to complete the project which has been published a high impact journal, Arterioscler Thromb Vasc Biol. I would also like to thank for their help with …