Fabp4-KO Mouse

Fabp4, also known as fatty acid binding protein 4 or aP2, is a cytoplasmic fatty acid chaperone. It is highly expressed in adipose tissue and myeloid cells, playing a crucial role in lipid metabolism. It functions as a lipid chaperone protein and is involved in pathways related to energy storage and communication between different organs. It has been associated with many biological processes and diseases, making it an important target for research, and genetic models such as KO mouse models are valuable for studying its functions [2,5].

Knockdown of Fabp4 in ovarian cancer cells led to increased 5-hydroxymethylcytosine levels in DNA, downregulation of metastasis-associated gene signatures, and reduced clonogenic survival. CRISPR-mediated knockout of Fabp4 in high-grade serous ovarian cancer cells decreased metastatic tumor burden in mice, and a small-molecule inhibitor of Fabp4 reduced tumor burden and increased carboplatin sensitivity [1]. In elderly mice, silencing Fabp4 rejuvenated aging-associated decline in metabolic activities, reversed metabolic disorders by promoting cholesterol and fatty acid degradation while suppressing gluconeogenesis [3]. In TNBC, knocking down Fabp4 or inhibiting its activity suppressed tumor progression in mouse models [4].

In conclusion, Fabp4 is essential in lipid metabolism and is involved in various disease conditions. Findings from Fabp4 KO/CKO mouse models and knockdown experiments have revealed its role in cancer metastasis, metabolic disorders in the elderly, and TNBC progression. These studies provide valuable insights into potential therapeutic targets for treating related diseases.

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. 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/