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TM6SF2 is a regulator of liver fat metabolism influencing triglyceride secretion and hepatic lipid droplet content

2014; National Academy of Sciences; Volume: 111; Issue: 24 Linguagem: Inglês

10.1073/pnas.1323785111

1091-6490

Hovsep Mahdessian, Apostolos Taxiarchis, Sergej Popov, Angela Silveira, Anders Franco‐Cereceda, Anders Hamsten, Per Eriksson, Ferdinand van’t Hooft,

Lipid metabolism and disorders

Significance Genome-wide association studies have uncovered a genetic locus in chromosome 19 associated with the plasma triglyceride (TG) concentration, a risk factor for coronary heart disease. The identity and functional role of the gene responsible for this association is unknown. Gene expression analysis of 206 human liver samples led to the identification of transmembrane 6 superfamily member 2 ( TM6SF2 ), a gene with hitherto unknown function, as the putative causal gene. Functional studies in human liver cells demonstrated that inhibition of TM6SF2 was associated with reduced secretion of TG-rich lipoproteins (TRLs) and increased cellular TG concentration, while TM6SF2 overexpression reduced cellular TG concentration. We conclude that TM6SF2 is a novel regulator of liver fat metabolism with opposing effects on the secretion of TRLs and hepatic TG content.