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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 diseaseprotecting 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.
Advisor: Qiaozhu Su