Fabp1, also known as liver-type fatty acid binding protein, plays a pivotal role in fatty acid metabolism. It is involved in intracellular fatty acid transport and may participate in pathways related to lipid homeostasis, such as the peroxisome proliferator-activated receptor (PPAR)-related pathways. Its importance extends to various biological processes like maintaining normal cell function in tissues with high fatty acid metabolism demands [2,3,4].

In hepatocellular carcinoma (HCC), FABP1 was overexpressed in tumor-associated macrophages (TAMs) of III-stage compared to II-stage cases. FABP1 deficiency in TAMs inhibited HCC progression in vitro and in vivo in a C57BL/6 mouse model. Mechanistically, it interacted with PPARG/CD36 in TAMs to increase fatty acid oxidation in HCC. Also, in FABP1 -/- mice, there were changes in the relative proportion of immune cells, with regulatory T cells and natural killer cells showing a downward trend, while dendritic cells, M1 macrophages, and B cells showed an upward trend [1]. In IgA nephropathy, downregulation of PPARα reduced FABP1 expression, affecting GPX4 and ACSL4 levels, causing ferroptosis in human mesangial cells [2]. In non-alcoholic steatohepatitis (NASH), intestine-specific disruption of Ppara or Fabp1 in mice fed a high-fat diet decreased obesity-associated metabolic disorders and NASH. Intestinal PPARα induced FABP1 expression, which mediated fatty acid uptake [4]. In non-alcoholic fatty liver disease (NAFLD), Derlin-1 interacted with and ubiquitinated FABP1, suppressing FABP1 levels and lipid deposition. Overexpression of Derlin-1 in C57BL/6 mice and HepG2 cells ameliorated hepatic steatosis [5].

In conclusion, Fabp1 is crucial for fatty acid metabolism-related functions. Gene knockout mouse models have revealed its significant roles in diseases such as HCC, IgA nephropathy, NASH, and NAFLD, highlighting its potential as a therapeutic target in these disease areas.

References:

1. Tang, Weiwei, Sun, Guangshun, Ji, Gu-Wei, Xia, Yongxiang, Wang, Xuehao. 2023. Single-cell RNA-sequencing atlas reveals an FABP1-dependent immunosuppressive environment in hepatocellular carcinoma. In Journal for immunotherapy of cancer, 11, . doi:10.1136/jitc-2023-007030. https://pubmed.ncbi.nlm.nih.gov/38007237/

2. Wu, Jingkui, Shao, Xinghua, Shen, Jianxiao, Qi, Chaojun, Ni, Zhaohui. 2022. Downregulation of PPARα mediates FABP1 expression, contributing to IgA nephropathy by stimulating ferroptosis in human mesangial cells. In International journal of biological sciences, 18, 5438-5458. doi:10.7150/ijbs.74675. https://pubmed.ncbi.nlm.nih.gov/36147466/

3. Dum, David, Ocokoljic, Ana, Lennartz, Maximilian, Blessin, Niclas C, Krech, Till. 2022. FABP1 expression in human tumors: a tissue microarray study on 17,071 tumors. In Virchows Archiv : an international journal of pathology, 481, 945-961. doi:10.1007/s00428-022-03394-5. https://pubmed.ncbi.nlm.nih.gov/35951102/

4. Yan, Tingting, Luo, Yuhong, Yan, Nana, Qu, Aijuan, Gonzalez, Frank J. 2022. Intestinal peroxisome proliferator-activated receptor α-fatty acid-binding protein 1 axis modulates nonalcoholic steatohepatitis. In Hepatology (Baltimore, Md.), 77, 239-255. doi:10.1002/hep.32538. https://pubmed.ncbi.nlm.nih.gov/35460276/

5. You, Hui, Wen, Xin, Wang, Xingchun, Zhang, Jun, Qu, Shen. 2023. Derlin-1 ameliorates nonalcoholic hepatic steatosis by promoting ubiquitylation and degradation of FABP1. In Free radical biology & medicine, 207, 260-271. doi:10.1016/j.freeradbiomed.2023.07.026. https://pubmed.ncbi.nlm.nih.gov/37499886/