Fabp4, also known as fatty acid binding protein 4 or aP2, is a cytoplasmic fatty acid chaperone. It plays a crucial role in lipid metabolism, and is highly expressed in adipose tissue and myeloid cells. FABP4 is involved in multiple pathways, such as affecting cells through JAK2/STAT2 and c-kit pathways, and is linked to maintaining glucose homeostasis. It also has implications in the development of various diseases including insulin resistance, atherosclerosis, and cancer [2,5,6]. Genetic models, like KO/CKO mouse models, are valuable for studying its functions.

In ovarian cancer, knockdown of FABP4 led to increased 5-hydroxymethylcytosine levels in DNA, down-regulation of metastasis-associated gene signatures, and reduced clonogenic cancer cell survival. CRISPR-mediated knockout in high-grade serous ovarian cancer cells decreased metastatic tumor burden in mice. In addition, a small-molecule inhibitor of FABP4 reduced tumor burden and increased carboplatin sensitivity in a mouse model [1]. In TNBC, knocking down Fabp4 or inhibiting its activity suppressed tumor progression in mouse models, and its influence was related to mitochondrial stability, fatty acid oxidation, and ROS production [4]. In elderly mice, silencing FABP4 rejuvenated liver metabolism and improved aging-associated metabolic disorders [3].

In summary, Fabp4 is essential in lipid metabolism and maintaining glucose homeostasis. KO/CKO mouse models have revealed its significant roles in cancer metastasis, aging-associated metabolic disorders, and potentially other disease areas like TNBC. These findings offer potential therapeutic targets for treating related diseases by targeting FABP4 [1,3,4].

References:

1. Mukherjee, Abir, Chiang, Chun-Yi, Daifotis, Helen A, Fiehn, Oliver, Lengyel, Ernst. 2020. Adipocyte-Induced FABP4 Expression in Ovarian Cancer Cells Promotes Metastasis and Mediates Carboplatin Resistance. In Cancer research, 80, 1748-1761. doi:10.1158/0008-5472.CAN-19-1999. https://pubmed.ncbi.nlm.nih.gov/32054768/

2. Garin-Shkolnik, Tali, Rudich, Assaf, Hotamisligil, Gökhan S, Rubinstein, Menachem. 2013. FABP4 attenuates PPARγ and adipogenesis and is inversely correlated with PPARγ in adipose tissues. In Diabetes, 63, 900-11. doi:10.2337/db13-0436. https://pubmed.ncbi.nlm.nih.gov/24319114/

3. Lv, Jian, Hu, Yimeng, Li, Lili, Tang, Lixu, Wang, Zhihua. 2023. Targeting FABP4 in elderly mice rejuvenates liver metabolism and ameliorates aging-associated metabolic disorders. In Metabolism: clinical and experimental, 142, 155528. doi:10.1016/j.metabol.2023.155528. https://pubmed.ncbi.nlm.nih.gov/36842611/

4. Yu, Liya, Wei, Wei, Lv, Jian, Wang, Zhihua, Cai, Cheguo. 2024. FABP4-mediated lipid metabolism promotes TNBC progression and breast cancer stem cell activity. In Cancer letters, 604, 217271. doi:10.1016/j.canlet.2024.217271. https://pubmed.ncbi.nlm.nih.gov/39306229/

5. van der Ark-Vonk, Ellen M, Puijk, Mike V, Pasterkamp, Gerard, van der Laan, Sander W. 2024. The Effects of FABP4 on Cardiovascular Disease in the Aging Population. In Current atherosclerosis reports, 26, 163-175. doi:10.1007/s11883-024-01196-5. https://pubmed.ncbi.nlm.nih.gov/38698167/

6. Prentice, Kacey J, Saksi, Jani, Hotamisligil, Gökhan S. 2019. Adipokine FABP4 integrates energy stores and counterregulatory metabolic responses. In Journal of lipid research, 60, 734-740. doi:10.1194/jlr.S091793. https://pubmed.ncbi.nlm.nih.gov/30705117/