ArticleGastroenterology2016
Hepatic Transmembrane 6 Superfamily Member 2 Regulates Cholesterol Metabolism in Mice.
Article in Gastroenterology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 4 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
60 citing papers in PubMed, 4 syntheses or guidelines pooled it, 91 citations in OpenAlex.
- TM6SF2 rs58542926 is related to hepatic steatosis, fibrosis and serum lipids both in adults and children: A meta-analysis.Frontiers in endocrinology · 2022Pooled it
- Association of TM6SF2 rs58542926 T/C gene polymorphism with hepatocellular carcinoma: a meta-analysis.BMC cancer · 2019Pooled it
- The effect of the TM6SF2 E167K variant on liver steatosis and fibrosis in patients with chronic hepatitis C: a meta-analysis.Scientific reports · 2017Pooled it
- Meta-analysis of the influence of TM6SF2 E167K variant on Plasma Concentration of Aminotransferases across different Populations and Diverse Liver Phenotypes.Scientific reports · 2016Pooled it
- Lipid nanoparticle-mediated transcription factor EB mRNA delivery for the treatment of metabolic dysfunction-associated steatotic liver disease.Molecular biomedicine · 2026Article
- Early lipid genetics: identification of common and rare genetic variants for lipid traits in Indian adolescents.Journal of human genetics · 2025Article
- Maternal cholesterol deficiency predisposes congenital heart defects risk.Signal transduction and targeted therapy · 2025Article
- Human-induced pluripotent stem cell-based hepatic modeling of lipid metabolism-associated TM6SF2-E167K variant.Hepatology (Baltimore, Md.) · 2025Article
- [Research progress on clinical characteristics and pathological mechanisms of lean metabolic-associated fatty liver disease].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2025Review
- Gene-based therapies for steatotic liver disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Intestinal TM6SF2 protects against metabolic dysfunction-associated steatohepatitis through the gut-liver axis.Nature metabolism · 2025Article
- PNPLA3 is one of the bridges between TM6SF2 E167K variant and MASLD: Correspondence to editorial on "TM6SF2 E167K variant decreases PNPLA3-mediated PUFA transfer to promote hepatic steatosis and injury in MASLD".Clinical and molecular hepatology · 2025Article
- Deep metabolic phenotyping of humans with protein-altering variants inJHEP reports : innovation in hepatology · 2025Article
- TM6SF2 E167K variant decreases PNPLA3-mediated PUFA transfer to promote hepatic steatosis and injury in MASLD.Clinical and molecular hepatology · 2024Article
- CD9 Counteracts Liver Steatosis and Mediates GCGR Agonist Hepatic Effects.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- MESuSiE enables scalable and powerful multi-ancestry fine-mapping of causal variants in genome-wide association studies.Nature genetics · 2024Article
- Exploring the impact of lipid droplets on the evolution and progress of hepatocarcinoma.Frontiers in cell and developmental biology · 2024Review
- A study of genetic variants, genetic risk score and DNA methylation of PNPLA3 and TM6SF2 in alcohol liver cirrhosis.Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology · 2023Article
- Unraveling the pathogenesis of non-alcoholic fatty liver diseases through genome-wide association studies.Journal of gastroenterology and hepatology · 2023Review
- Mechanisms Behind NAFLD: a System Genetics Perspective.Current atherosclerosis reports · 2023Review
Corrections and comments
- Commented on byReply.2016
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsThe 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.
methodsC57BL/6 mice (controls), mice that expressed TM6SF2 specifically in the liver, and mice with CRISPR/Cas9-mediated knockout of Tm6sf2 were fed chow or high-fat diets. Blood samples were collected from all mice and plasma levels of TC, low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol, and triglycerides were measured. Liver tissues were collected and analyzed by histology, real-time polymerase chain reaction, and immunoblot assays. Adenovirus vectors were used to express transgenes in cultured Hep3B hepatocytes.
resultsLiver-specific expression of TM6SF2 increased plasma levels of TC and LDL-c, compared with controls, and altered liver expression of genes that regulate cholesterol metabolism. Tm6sf2-knockout mice had decreased plasma levels of TC and LDL-c, compared with controls, and consistent changes in expression of genes that regulate cholesterol metabolism. Expression of TM6SF2 promoted cholesterol biosynthesis in hepatocytes.
conclusionsTM6SF2 regulates cholesterol metabolism in mice and might be a therapeutic target for cardiovascular disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.