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.

跨膜 4 L 六族成员 5 (TM4SF5) 参与非酒精性脂肪变性和肝病的进一步加重。然而，其调节 FA 积累的机制尚不清楚。我们研究了在急性 FA 供应期间肝细胞中的 TM4SF5 如何影响 FA 积累。与 TM4SF5 缺乏或失活的肝细胞和小鼠肝脏相比，表达 TM4SF5 的肝细胞和小鼠肝脏积累的 F​​As 较少。TM4SF5 与 SLC27A2 的结合在急性 FA 治疗后逐渐增加，而 TM4SF5 组成性地结合 SLC27A5。在表达 TM4SF5 的肝细胞中抑制 SLC27A2 或 SLC27A5 会差异调节初始和最大 FA 摄取水平，以实现脂肪酸的快速周转。总而言之，TM4SF5 通过与转运蛋白的结合来负向调节 FA 在肝细胞中的积累，以实现能量稳态，