7 results match your criteria tm6sf2 knockout

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Liver specific deletion of mouse Tm6sf2 promotes steatosis, fibrosis and hepatocellular cancer.

Hepatology 2021 Feb 27. Epub 2021 Feb 27.

Department of Medicine, Washington University School of Medicine, St. Louis, MO, 63110, United States.

Background And Aims: Human TM6SF2 variant rs58542926 is associated with nonalcoholic fatty liver disease (NAFLD) and hepatocellular cancer (HCC). However, conflicting reports in germline Tm6sf2 knockout mice suggest no change or decreased VLDL secretion and either unchanged or increased hepatic steatosis, with no increased fibrosis. We generated liver specific Tm6Sf2 knockout mice (Tm6 LKO) to study VLDL secretion and the impact on development and progression of NAFLD. Read More

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February 2021

Disruption of the ERLIN-TM6SF2-APOB complex destabilizes APOB and contributes to non-alcoholic fatty liver disease.

PLoS Genet 2020 08 10;16(8):e1008955. Epub 2020 Aug 10.

Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, China.

Non-alcoholic fatty liver disease (NAFLD) is a metabolic disorder characterized by excess lipid accumulation in the liver without significant consumption of alcohol. The transmembrane 6 superfamily member 2 (TM6SF2) E167K missense variant strongly associates with NAFLD in humans. The E167K mutation destabilizes TM6SF2, resulting in hepatic lipid accumulation and low serum lipid levels. Read More

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Hepatic Carbohydrate Response Element Binding Protein Activation Limits Nonalcoholic Fatty Liver Disease Development in a Mouse Model for Glycogen Storage Disease Type 1a.

Hepatology 2020 11 30;72(5):1638-1653. Epub 2020 Oct 30.

Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.

Background And Aims: Glycogen storage disease (GSD) type 1a is an inborn error of metabolism caused by defective glucose-6-phosphatase catalytic subunit (G6PC) activity. Patients with GSD 1a exhibit severe hepatomegaly due to glycogen and triglyceride (TG) accumulation in the liver. We have shown that the activity of carbohydrate response element binding protein (ChREBP), a key regulator of glycolysis and de novo lipogenesis, is increased in GSD 1a. Read More

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November 2020

TM6SF2: A novel target for plasma lipid regulation.

Atherosclerosis 2018 01 1;268:170-176. Epub 2017 Dec 1.

Institute of Cardiovascular Disease, Key Lab for Arteriosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, China; Department of Biochemistry and Molecular Biology, The Libin Cardiovascular Institute of Alberta, The University of Calgary, Health Sciences Center, 3330 Hospital Drive NW, Calgary, Alberta T2N 4N1, Canada. Electronic address:

Transmembrane 6 superfamily 2 (TM6SF2), a gene identified at the locus 19p12, has been recognized to regulate plasma lipids. Here, we provide an overview of the roles of TM6SF2 as a novel target for plasma lipid regulation. We first review the association of TM6SF2 variant with plasma lipid traits, cardiovascular disease (CVD) and non-alcoholic fatty liver disease (NAFLD). Read More

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January 2018

Hepatic Tm6sf2 overexpression affects cellular ApoB-trafficking, plasma lipid levels, hepatic steatosis and atherosclerosis.

Hum Mol Genet 2017 07;26(14):2719-2731

Department of Basic Medical Sciences, Western University of Health Sciences, Pomona, CA 91766, USA.

The human transmembrane 6 superfamily member 2 (TM6SF2) gene has been implicated in plasma lipoprotein metabolism, alcoholic and non-alcoholic fatty liver disease and myocardial infarction in multiple genome-wide association studies. To investigate the role of Tm6sf2 in metabolic homeostasis, we generated mice with elevated expression using adeno-associated virus (AAV)-mediated gene delivery. Hepatic overexpression of mouse Tm6sf2 resulted in phenotypes previously observed in Tm6sf2-deficient mice including reduced plasma lipid levels, diminished hepatic triglycerides secretion and increased hepatosteatosis. Read More

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Inactivation of Tm6sf2, a Gene Defective in Fatty Liver Disease, Impairs Lipidation but Not Secretion of Very Low Density Lipoproteins.

J Biol Chem 2016 May 24;291(20):10659-76. Epub 2016 Mar 24.

From the Departments of Molecular Genetics and Internal Medicine and the Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390

A missense mutation (E167K) in TM6SF2 (transmembrane 6 superfamily member 2), a polytopic protein of unknown function, is associated with the full spectrum of fatty liver disease. To investigate the role of TM6SF2 in hepatic triglyceride (TG) metabolism, we inactivated the gene in mice. Chronic inactivation of Tm6sf2 in mice is associated with hepatic steatosis, hypocholesterolemia, and transaminitis, thus recapitulating the phenotype observed in humans. Read More

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Hepatic Transmembrane 6 Superfamily Member 2 Regulates Cholesterol Metabolism in Mice.

Gastroenterology 2016 05 13;150(5):1208-1218. Epub 2016 Jan 13.

Cardiovascular Center, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan. Electronic address:

Background & Aims: The rs58542926 C>T variant of the transmembrane 6 superfamily member 2 gene (TM6SF2), encoding an E167K amino acid substitution, has been correlated with reduced total cholesterol (TC) and cardiovascular disease. However, little is known about the role of TM6SF2 in metabolism. We investigated the long-term effects of altered TM6SF2 levels in cholesterol metabolism. Read More

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