ArticleHepatology (Baltimore, Md.)2017
TM6SF2 rs58542926 impacts lipid processing in liver and small intestine.
Article in Hepatology (Baltimore, Md.), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 86 citations in OpenAlex.
- Meta-Analysis: Effects of Steatotic Liver Disease-Associated Genetic Risk Alleles on Longitudinal Outcomes.Alimentary pharmacology & therapeutics · 2025Pooled it
- A UFMylation-COPII axis orchestrates lipid transport in intestinal enterocytes and regulates systemic lipid balance.Molecular metabolism · 2026Article
- Hepatic Lipoprotein Production, Cardiometabolic Phenotypes, and Subtypes of Steatotic Liver Disease.Circulation research · 2026Review
- Biomarkers for early identification of metabolic dysfunction-associated steatotic liver disease (MASLD): a narrative review.Archives of medical science : AMS · 2026Article
- Modeling Transmembrane 6 Superfamily Member 2 p.Glu167Lys-associated Steatotic Liver Disease Using Androgen-treated Human Induced Pluripotent Stem Cell-derived Hepatocyte-like Cells.Gastro hep advances · 2026Article
- Present and Future Perspectives in the Treatment of Liver Fibrosis.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Intestinal Depletion of TM6SF2 Exacerbates High-fat Diet-induced Metabolic Dysfunction-associated Steatotic Liver Disease through the Gut-liver Axis.Journal of clinical and translational hepatology · 2025Article
- The intracellular chylomicron highway: novel insights into chylomicron biosynthesis, trafficking, and secretion.Current opinion in lipidology · 2025Review
- The Role of Extracellular Vesicles in the Pathogenesis of Metabolic Dysfunction-Associated Steatotic Liver Disease and Other Liver Diseases.International journal of molecular sciences · 2025Review
- A Defective Circulating Mitochondrial Bioenergetics Profile Reflects the Hepatic One and Outlines Genetic MASLD.Antioxidants (Basel, Switzerland) · 2025Article
- Precision medicine and nucleotide-based therapeutics to treat steatotic liver disease.Clinical and molecular hepatology · 2025Review
- Intestinal TM6SF2 protects against metabolic dysfunction-associated steatohepatitis through the gut-liver axis.Nature metabolism · 2025Article
- TM6SF2 as new intestinal lipid player.Nature metabolism · 2025Article
- Deep metabolic phenotyping of humans with protein-altering variants inJHEP reports : innovation in hepatology · 2025Article
- Review
- Gut microbes, diet, and genetics as drivers of metabolic liver disease: a narrative review outlining implications for precision medicine.The Journal of nutritional biochemistry · 2024Review
- Pla2g12b drives expansion of triglyceride-rich lipoproteins.Nature communications · 2024Article
- MESuSiE enables scalable and powerful multi-ancestry fine-mapping of causal variants in genome-wide association studies.Nature genetics · 2024Article
- Nonalcoholic Fatty Liver Disease-Related Hepatocellular Carcinoma: The Next Threat after Viral Hepatitis.Diagnostics (Basel, Switzerland) · 2023Review
- Evolution of Spatial and Temporal cis-Regulatory Divergence in Sticklebacks.Molecular biology and evolution · 2023Article
Corrections and comments
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Authors and funding
18 authors at 4 institutions in 1 country.
Funding
Abstract
The transmembrane 6 superfamily member 2 (TM6SF2) loss-of-function variant rs58542926 is a genetic risk factor for nonalcoholic fatty liver disease and progression to fibrosis but is paradoxically associated with lower levels of hepatically derived triglyceride-rich lipoproteins. TM6SF2 is expressed predominantly in liver and small intestine, sites for triglyceride-rich lipoprotein biogenesis and export. In light of this, we hypothesized that TM6SF2 may exhibit analogous effects on both liver and intestine lipid homeostasis. To test this, we genotyped rs58542926 in 983 bariatric surgery patients from the Geisinger Medical Center for Nutrition and Weight Management, Geisinger Health System, in Pennsylvania and from 3,556 study participants enrolled in the Amish Complex Disease Research Program. Although these two cohorts have different metabolic profiles, carriers in both cohorts had improved fasting lipid profiles. Importantly, following a high-fat challenge, carriers in the Amish Complex Disease Research Program cohort exhibited significantly lower postprandial serum triglycerides, suggestive of a role for TM6SF2 in the small intestine. To gain further insight into this putative role, effects of TM6SF2 deficiency were studied in a zebrafish model and in cultured human Caco-2 enterocytes. In both systems TM6SF2 deficiency resulted in defects in small intestine metabolism in response to dietary lipids, including significantly increased lipid accumulation, decreased lipid clearance, and increased endoplasmic reticulum stress.
conclusionsThese data strongly support a role of TM6SF2 in the regulation of postprandial lipemia, potentially through a similar function for TM6SF2 in the lipidation and/or export of both hepatically and intestinally derived triglyceride-rich lipoproteins. (Hepatology 2017;65:1526-1542).
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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.