Journal
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
Volume 710, Issue -, Pages -Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2021.109004
Keywords
Fatty acid accumulation; beta-oxidation; Hepatocytes; SLC27As; Tetraspan
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Funding
- Basic Science Research Program throughthe National Research Foundation of Korea (NRF) - Min-istry of Science, ICT & Future Planning [NRF-2020R1I1A1A01070020, 2020R1A2C3008993, NRF-2021M3A9D3024752]
- National Research Foundation of Korea [2020R1A2C3008993] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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TM4SF5 negatively modulates the accumulation of fatty acids in hepatocytes by associating with transporters during acute fatty acid supply, contributing to energy homeostasis.
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.
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