Key Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs), Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, 5 Yushan Road, Qingdao, 266003, Shandong, People's Republic of China.
FASEB J. 2024 Sep 30;38(18):e70036. doi: 10.1096/fj.202401087RR.
Fatty acid-binding protein 1 (FABP1) plays an important role in regulating fatty acid metabolism in liver, which is a potential therapeutic target for diseases such as non-alcoholic fatty liver disease (NAFLD). However, the underlying mechanisms are not well defined. Using complementary experimental models, we discovered FABP1 induction in hepatocytes as a primary mediator of lipogenesis when exposed to fatty acids, especially saturated fatty acids (SFAs). In the feeding trial, palm oil led to excess lipid accumulation in the liver of large yellow croaker (Larimichthys crocea), accompanied by significant induction of FABP1. In cultured cells, palmitic acid (PA), a kind of SFA, triggered the fabp1 expression and increased triglyceride (TG) contents. Knockdown of FABP1 dampened PA-induced TG accumulation through mitigated lipogenesis. The overexpression of FABP1 showed the opposite result. Furthermore, the inactivation of FABP1 led to induction in insulin-induced gene 1 (INSIG1) expression, which attenuated the processing of sterol regulatory element-binding protein 1 (SREBP1) by down-regulating the nuclear-localized SREBP1. These results revealed a previously unrecognized function of FABP1 in response to PA, providing additional evidence for targeting FABP1 in the treatment of NAFLD caused by SFA.
脂肪酸结合蛋白 1（FABP1）在肝脏的脂肪酸代谢调节中发挥重要作用，是治疗非酒精性脂肪性肝病（NAFLD）等疾病的潜在治疗靶点。然而，其潜在机制尚不清楚。通过互补的实验模型，我们发现脂肪酸，尤其是饱和脂肪酸（SFAs）暴露时，肝细胞中 FABP1 的诱导是脂肪生成的主要介质。在喂养试验中，棕榈油导致大黄鱼（Larimichthys crocea）肝脏中脂质过度积累，同时 FABP1 显著诱导。在培养的细胞中，棕榈酸（PA），一种 SFA，触发 fabp1 表达并增加甘油三酯（TG）含量。FABP1 的敲低通过减轻脂肪生成减弱了 PA 诱导的 TG 积累。FABP1 的过表达则显示出相反的结果。此外，FABP1 的失活导致胰岛素诱导基因 1（INSIG1）的表达诱导，通过下调核定位的 SREBP1 来减弱固醇调节元件结合蛋白 1（SREBP1）的加工。这些结果揭示了 FABP1 在 PA 反应中的一个先前未被认识的功能，为针对 SFA 引起的 NAFLD 靶向 FABP1 提供了额外的证据。
