Tetraspanin TM4SF5 in hepatocytes negatively modulates SLC27A transporters during acute fatty acid supply

Dasomi Park; Eunmi Kim; Haesong Lee; Eun-Ae Shin; Hyejin Lee; Jung Weon Lee

doi:10.1016/j.abb.2021.109004

Tetraspanin TM4SF5 in hepatocytes negatively modulates SLC27A transporters during acute fatty acid supply

Arch Biochem Biophys. 2021 Oct 15:710:109004. doi: 10.1016/j.abb.2021.109004. Epub 2021 Aug 6.

Authors

Dasomi Park¹, Eunmi Kim¹, Haesong Lee¹, Eun-Ae Shin¹, Hyejin Lee¹, Jung Weon Lee²

Affiliations

¹ Department of Pharmacy, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, 08826, South Korea.
² Department of Pharmacy, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, 08826, South Korea. Electronic address: jwl@snu.ac.kr.

PMID: 34364885
DOI: 10.1016/j.abb.2021.109004

Abstract

Transmembrane 4 L six family member 5 (TM4SF5) is involved in nonalcoholic steatosis and further aggravation of liver disease. However, its mechanism for regulating FA accumulation is unknown. We investigated how TM4SF5 in hepatocytes affected FA accumulation during acute FA supply. TM4SF5-expressing hepatocytes and mouse livers accumulated less FAs, compared with those of TM4SF5 deficiency or inactivation. Binding of TM4SF5 to SLC27A2 increased gradually upon acute FA treatment, whereas TM4SF5 constitutively bound SLC27A5. Suppression of either SLC27A2 or SLC27A5 in hepatocytes expressing TM4SF5 differentially modulated initial and maximal FA uptake levels for a fast turnover of fatty acid. Altogether, TM4SF5 negatively modulates FA accumulation into hepatocytes via association with the transporters for an energy homeostasis, when FA are supplied acutely.

Keywords: Fatty acid accumulation; Hepatocytes; SLC27As; Tetraspan; β-oxidation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Biological Transport, Active
Cell Line
Energy Metabolism
Fatty Acid Transport Proteins / antagonists & inhibitors
Fatty Acid Transport Proteins / genetics
Fatty Acid Transport Proteins / metabolism*
Fatty Acids / metabolism*
HEK293 Cells
Hep G2 Cells
Hepatocytes / metabolism*
Humans
Membrane Proteins / antagonists & inhibitors
Membrane Proteins / deficiency
Membrane Proteins / genetics
Membrane Proteins / metabolism*
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Models, Biological
Non-alcoholic Fatty Liver Disease / etiology
Non-alcoholic Fatty Liver Disease / metabolism
Oxygen Consumption
RNA, Small Interfering / genetics

Substances

Fatty Acid Transport Proteins
Fatty Acids
Membrane Proteins
RNA, Small Interfering
TM4SF5 protein, human
TM4SF5 protein, mouse