Low-Density Lipoprotein Receptor Signaling Mediates the Triglyceride-Lowering Action of Akkermansia muciniphila in Genetic-Induced Hyperlipidemia
Autor: | Rituraj Khound, Xuedong Tong, Qiaozhu Su, Neetu Sud, Jens Walter, Jing Shen, Yongyan Song, Maria X. Maldonado-Gomez |
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Rok vydání: | 2015 |
Předmět: |
0301 basic medicine
medicine.medical_specialty Time Factors Down-Regulation 030204 cardiovascular system & hematology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Insulin resistance Apolipoproteins E Verrucomicrobia Internal medicine Hyperlipidemia Chylomicrons medicine Animals Genetic Predisposition to Disease Cyclic AMP Response Element-Binding Protein Triglycerides Hypertriglyceridemia Mice Knockout biology Triglyceride medicine.disease biology.organism_classification Endoplasmic Reticulum Stress Gastrointestinal Microbiome Gastrointestinal Tract Mice Inbred C57BL Disease Models Animal 030104 developmental biology Postprandial Endocrinology Phenotype chemistry Lipoproteins IDL Liver Receptors LDL LDL receptor Apolipoprotein B-100 Host-Pathogen Interactions Insulin Resistance Cardiology and Cardiovascular Medicine Akkermansia muciniphila Biomarkers Chylomicron Signal Transduction |
Zdroj: | Arteriosclerosis, thrombosis, and vascular biology. 36(7) |
ISSN: | 1524-4636 |
Popis: | Objective— 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 mellitus 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. Approach and Results— By establishing a novel mouse model that colonized the A muciniphila in the gastrointestinal 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 gastrointestinal tract of wild-type mice protected mice from an acute fat load–induced hyperlipidemia compared with vehicle-treated mice. A muciniphila administration also significantly ameliorated chronic hypertriglyceridemia, improved insulin sensitivity, and prevented overproduction of postprandial chylomicrons in CREBH-null mice. Mechanistic studies revealed that increased A muciniphila colonization induced expression of low-density lipoprotein receptors and apolipoprotein E in the hepatocytes of CREBH-null mice, which facilitated the uptake of intermediate-density lipoprotein via the mediation of apolipoprotein B100 and apolipoprotein E, leading to the increased clearance of triglyceride-rich lipoprotein remnants, chylomicron remnants, and intermediate-density lipoproteins, from the circulation. Treatment with A muciniphila further improved hepatic endoplasmic reticulum stress and metabolic inflammation in CREBH-null mice. Conclusions— Increased colonization of the disease-protective gut bacteria A muciniphila protected the host from acute and chronic hyperlipidemia by enhancing the low-density lipoprotein receptor expression and alleviating hepatic endoplasmic reticulum stress and the inflammatory response in CREBH-null mice. |
Databáze: | OpenAIRE |
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