Fabp5, also known as epidermal fatty acid binding protein (E-FABP), is an intracellular chaperone of fatty acid molecules. It regulates lipid metabolism by transporting fatty acids to nuclear receptors like peroxisome proliferator-activated receptors (PPARs), thus facilitating their activation, and is involved in various biological processes including cell growth [4].

In hepatocellular carcinoma (HCC), FABP5+ lipid-loaded macrophages are identified. Macrophage-specific FABP5 deficiency in mice decreases immunosuppressive molecule expression, enhances T-cell-dependent antitumor immunity, reduces HCC growth, and improves immunotherapy efficacy, indicating that FABP5-mediated unsaturated fatty acid metabolism in macrophages modulates antitumor T-cell immunity [1]. In allergic asthma, myeloid-specific deletion of FABP5 in mice exacerbates OVA-induced allergic airway inflammation by increasing alternatively activated macrophages (M2), suggesting FABP5 controls macrophage alternative activation through programming long-chain unsaturated fatty acid metabolism [2]. In psoriasis, genetic deletion of FABP5 in mice (global knockout and keratinocyte conditional knockout) attenuates psoriatic symptoms by reducing skin recruitment of Ly6G+ neutrophils, showing FABP5-VCP complex in keratinocytes mediates neutrophil infiltration [3].

In conclusion, Fabp5 is crucial in lipid metabolism-related biological processes. Gene-knockout mouse models, such as macrophage-specific, myeloid-specific, global, and cell-type-specific conditional knockouts, have revealed its role in diseases like HCC, allergic asthma, and psoriasis. These findings highlight Fabp5 as a potential therapeutic target in these disease areas.

References:

1. Yang, Xuguang, Deng, Bo, Zhao, Weiwei, Huang, Xiaowu, Lin, Yuli. 2024. FABP5+ lipid-loaded macrophages process tumour-derived unsaturated fatty acid signal to suppress T-cell antitumour immunity. In Journal of hepatology, 82, 676-689. doi:10.1016/j.jhep.2024.09.029. https://pubmed.ncbi.nlm.nih.gov/39357545/

2. Hou, Yangxiao, Wei, Dong, Zhang, Zhaoqi, Zhang, Lianfeng, Zhao, Yong. . FABP5 controls macrophage alternative activation and allergic asthma by selectively programming long-chain unsaturated fatty acid metabolism. In Cell reports, 41, 111668. doi:10.1016/j.celrep.2022.111668. https://pubmed.ncbi.nlm.nih.gov/36384126/

3. Hao, Jiaqing, Yu, Jianyu, Yorek, Matthew S, Jabbari, Ali, Li, Bing. 2023. Keratinocyte FABP5-VCP complex mediates recruitment of neutrophils in psoriasis. In Cell reports, 42, 113449. doi:10.1016/j.celrep.2023.113449. https://pubmed.ncbi.nlm.nih.gov/37967009/

4. George Warren, William, Osborn, Myles, Yates, Andy, Wright, Karen, O'Sullivan, Saoirse E. 2023. The emerging role of fatty acid binding protein 5 (FABP5) in cancers. In Drug discovery today, 28, 103628. doi:10.1016/j.drudis.2023.103628. https://pubmed.ncbi.nlm.nih.gov/37230284/