Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Jun 1;35(3):157-161.
doi: 10.1097/MOL.0000000000000930. Epub 2024 Mar 8.

Basic and translational evidence supporting the role of TM6SF2 in VLDL metabolism

Jing Liu  1 , Henry N Ginsberg, Gissette Reyes-Soffer
Affiliations
Review

Basic and translational evidence supporting the role of TM6SF2 in VLDL metabolism

Jing Liu et al. Curr Opin Lipidol. .

Abstract

Purpose of review: Transmembrane 6 superfamily member 2 ( TM6SF2 ) gene was identified through exome-wide studies in 2014. A genetic variant from glutamic acid to lysine substitution at amino acid position 167 (NM_001001524.3:c.499G> A) (p.Gln167Lys/p.E167K, rs58542926) was discovered (p.E167K) to be highly associated with increased hepatic fat content and reduced levels of plasma triglycerides and LDL cholesterol. In this review, we focus on the discovery of TM6SF2 and its role in VLDL secretion pathways. Human data suggest TM6SF2 is linked to hepatic steatosis and cardiovascular disease (CVD), hence understanding its metabolic pathways is of high scientific interest.

Recent findings: Since its discovery, completed research studies in cell, rodent and human models have defined the role of TM6SF2 and its links to human disease. TM6SF2 resides in the endoplasmic reticulum (ER) and the ER-Golgi interface and helps with the lipidation of nascent VLDL, the main carrier of triglycerides from the liver to the periphery. Consistent results from cells and rodents indicated that the secretion of triglycerides is reduced in carriers of the p.E167K variant or when hepatic TM6SF2 is deleted. However, data for secretion of APOB, the main protein of VLDL particles responsible for triglycerides transport, are inconsistent.

Summary: The identification of genetic variants that are highly associated with human disease presentation should be followed by the validation and investigation into the pathways that regulate disease mechanisms. In this review, we highlight the role of TM6SF2 and its role in processing of liver triglycerides.

PubMed Disclaimer

Conflict of interest statement

None.

Figures

Box 1
Box 1
no caption available
See this image and copyright information in PMC

References

    1. Johansen M, Moreno-Vedia J, Balling M, et al. . Triglyceride content increases while cholesterol content decreases in HDL and LDL+IDL fractions following normal meals: the Copenhagen General Population Study of 25,656 individuals. Atherosclerosis 2023; 383:117316. - PMC - PubMed
    1. Nordestgaard BG, Langlois MR, Langsted A, et al. . Quantifying atherogenic lipoproteins for lipid-lowering strategies: consensus-based recommendations from EAS and EFLM. Atherosclerosis 2020; 294:46–61. - PubMed
    1. Wegermann K, Moylan C, Naggie S. Fatty liver disease: enter the metabolic era. Curr HIV/AIDS Rep 2023; 20:405–418. - PubMed
    1. Eskridge W, Cryer DR, Schattenberg JM, et al. . Metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction-associated steatohepatitis: the patient and physician perspective. J Clin Med 2023; 12:6216. - PMC - PubMed
    1. Canivet CM, Faure S. [Diagnosis and evaluation of metabolic dysfunction associated steatotic liver disease (MASLD)]. Rev Med Interne 2024; 45:41–47. - PubMed

    2. The new terminology of MASLD replaces NAFLD. The latter follows the principal to include mechanisms related to the accumulation of fat in the liver.

Publication types