Fabp1, or liver-type fatty acid binding protein, plays a pivotal role in fatty acid metabolism. It binds and transports fatty acids within cells and is involved in pathways such as peroxisome proliferator-activated receptor (PPAR)-related signaling. Genetic models, like knockout mouse models, have been crucial in understanding its functions.

In hepatocellular carcinoma (HCC), FABP1 is overexpressed in tumor-associated macrophages (TAMs) of III-stage compared to II-stage cases. FABP1 deficiency in TAMs inhibits HCC progression in vitro and in vivo, as tumors in FABP1-/-mice show attenuation. The relative proportion of regulatory T cells and natural killer cells decreases, while dendritic cells, M1 macrophages, and B cells increase in FABP1-/-mice, indicating an FABP1-dependent immunosuppressive environment in HCC [1]. In IgA nephropathy, downregulation of PPARα reduces FABP1 expression, affecting GPX4 and ACSL4 levels, causing ferroptosis in human mesangial cells and contributing to the disease pathogenesis [2]. In non-alcoholic steatohepatitis (NASH), intestine-specific disruption of Ppara or Fabp1 in mice fed a high-fat diet decreases obesity-associated metabolic disorders and NASH, as intestinal PPARα induces FABP1 expression to modulate fatty acid uptake [3]. Also, Derlin-1, which interacts with FABP1, can ameliorate nonalcoholic hepatic steatosis by promoting FABP1 degradation [4].

In summary, Fabp1 is essential in fatty acid-related metabolic processes. Studies using Fabp1 knockout mouse models have revealed its significance in diseases like HCC, IgA nephropathy, and NASH. These models help in understanding the underlying mechanisms, providing potential targets for therapeutic interventions 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. 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/

4. 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/