ArticleClinical and molecular hepatology2024
TM6SF2 E167K variant decreases PNPLA3-mediated PUFA transfer to promote hepatic steatosis and injury in MASLD.
Article in Clinical and molecular hepatology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
13 citing papers in PubMed, 1 synthesis or guideline pooled it.
- High-protein diets and metabolic dysfunction-associated steatotic liver disease: A double-edged sword in liver health.World journal of gastroenterology · 2026Pooled it
- Metabolic dysfunction-associated steatotic liver disease and steatohepatitis-associated hepatocarcinoma preclinical models.Nature reviews. Gastroenterology & hepatology · 2026Review
- Current status survey and risk factor analysis of metabolic dysfunction-associated steatotic liver disease among adolescents in Hainan Province.Scientific reports · 2026Article
- Using an integrative multi-omics and in vitro approach to investigate the role of tris(2-butoxyethyl) phosphate in promoting hepatic steatosis.BMJ open gastroenterology · 2026Article
- Biomarkers for early identification of metabolic dysfunction-associated steatotic liver disease (MASLD): a narrative review.Archives of medical science : AMS · 2026Article
- Genetics and epigenetics in tumor necrosis factor-alpha (Frontiers in medicine · 2026Article
- Competing Cardiometabolic Pathways of Obesity and Metabolic Dysfunction-associated Steatotic Liver Disease.Gastro hep advances · 2026Article
- Lipid metabolism-MAFLD crosstalk: mechanisms and therapy.Frontiers in endocrinology · 2026Review
- Liver disease trends in the Asia-Pacific region for the next 50 years.Clinical and molecular hepatology · 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
- Causal roles of immune cells and metabolites in chronic pancreatitis: a mendelian randomization study.Hereditas · 2025Article
- TM6SF2 and PNPLA3: A potential dynamic duo?: Editorial on "TM6SF2 E167K variant decreases PNPLA3-mediated PUFA transfer to promote hepatic steatosis and injury in MASLD".Clinical and molecular hepatology · 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
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors.
Funding
Abstract
BACKGROUNDS/
aimsTransmembrane 6 superfamily member 2 (TM6SF2) E167K variant is closely associated with the occurrence and development of metabolic dysfunction-associated steatotic liver disease (MASLD). However, the role and mechanism of TM6SF2 E167K variant during MASLD progression are not yet fully understood.
methodsThe Tm6sf2167K knock-in (KI) mice were subjected to high-fat diet (HFD). Hepatic lipid levels of Tm6sf2167K KI mice were detected by lipidomics analysis. Thin-layer chromatography (TLC) was used to measure the newly synthesized triglyceride (TG) and phosphatidylcholine (PC).
resultsThe TM6SF2 E167K variant significantly aggravated hepatic steatosis and injury in HFD-induced mice. Decreased polyunsaturated PC level and increased polyunsaturated TG level were found in liver tissue of HFD-induced Tm6sf2167K KI mice. Mechanistic studies demonstrated that the TM6SF2 E167K variant increased the interaction between TM6SF2 and PNPLA3, and impaired PNPLA3-mediated transfer of polyunsaturated fatty acids (PUFAs) from TG to PC. The TM6SF2 E167K variant increased the level of fatty acid-induced malondialdehyde and reactive oxygen species, and decreased fatty acid-downregulated cell membrane fluidity. Additionally, the TM6SF2 E167K variant decreased the level of hepatic PC containing C18:3, and dietary supplementation of PC containing C18:3 significantly attenuated the TM6SF2 E167K-induced hepatic steatosis and injury in HFD-fed mice.
conclusionThe TM6SF2 E167K variant could promote its interaction with PNPLA3 and inhibit PNPLA3-mediated transfer of PUFAs from TG to PC, resulting in the hepatic steatosis and injury during MASLD progression. PC containing C18:3 could act as a potential therapeutic supplement for MASLD patients carrying the TM6SF2 E167K variant.
Indexed as
Identifiers
What OpenQuestion holds
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.