Fabp3-KO Mouse

Fabp3, also known as fatty acid binding protein 3, is a member of the cytoplasmic fatty acid binding protein family. It is predominantly expressed in breast, muscle, and heart tissues. Fabp3 is involved in lipid metabolism, where it binds and transports fatty acids, potentially affecting membrane lipid composition and related cellular functions [1,2,3,4,5]. It may be associated with pathways like the PERK-eIF2α pathway, ER stress response, and autophagy, and is of significance in maintaining cellular homeostasis [1,2]. Genetic models, such as gene knockout (KO) mouse models, are valuable for studying its functions.

In sarcopenia, Fabp3 is upregulated in aged skeletal muscles. KO of Fabp3 in aged muscles induces a young-like lipid composition, reduces ER stress, and improves protein synthesis and muscle recovery, indicating its role in regulating muscle homeostasis during aging [1]. In senile osteoporosis, knockdown of Fabp3 alleviates bone loss in aged mice as FABP3 promotes adipogenesis and inhibits osteogenesis of bone marrow mesenchymal stem cells (MSCs), and autophagy receptor OPTN regulates bone-fat balance by clearing FABP3 [2]. In cardiac hypertrophy, Fabp3 deficiency exacerbates metabolic derangement via the PPARα pathway, disrupting metabolic signatures like fatty acid oxidation and ATP production [5].

In conclusion, Fabp3 plays essential roles in lipid-related metabolic processes and cellular homeostasis. Model-based research, especially using KO mouse models, has revealed its significance in diseases such as sarcopenia, senile osteoporosis, and cardiac hypertrophy. Understanding Fabp3 functions provides insights into the underlying mechanisms of these diseases and potential therapeutic targets.

References:

1. Lee, Seung-Min, Lee, Seol Hee, Jung, Youngae, Lee, Kwang-Pyo, Kwon, Ki-Sun. 2020. FABP3-mediated membrane lipid saturation alters fluidity and induces ER stress in skeletal muscle with aging. In Nature communications, 11, 5661. doi:10.1038/s41467-020-19501-6. https://pubmed.ncbi.nlm.nih.gov/33168829/

2. Liu, Zheng-Zhao, Hong, Chun-Gu, Hu, Wen-Bao, Hu, Rong-Gui, Xie, Hui. 2020. Autophagy receptor OPTN (optineurin) regulates mesenchymal stem cell fate and bone-fat balance during aging by clearing FABP3. In Autophagy, 17, 2766-2782. doi:10.1080/15548627.2020.1839286. https://pubmed.ncbi.nlm.nih.gov/33143524/

3. Baru, Ambica, Devi, Chandra, Mukhopadhyay, Tapas, Dogra, Nilambra. 2023. Anti bacterial function of secreted human FABP3. In Biochimica et biophysica acta. General subjects, 1867, 130472. doi:10.1016/j.bbagen.2023.130472. https://pubmed.ncbi.nlm.nih.gov/37788726/

4. Wu, Sifan, Kong, Xiufang, Sun, Ying, Ma, Lili, Jiang, Lindi. . FABP3 overexpression promotes vascular fibrosis in Takayasu's arteritis by enhancing fatty acid oxidation in aorta adventitial fibroblasts. In Rheumatology (Oxford, England), 61, 3071-3081. doi:10.1093/rheumatology/keab788. https://pubmed.ncbi.nlm.nih.gov/34718429/

5. Zhuang, Lingfang, Mao, Ye, Liu, Zizhu, Yan, Xiaoxiang, Chen, Kang. 2021. FABP3 Deficiency Exacerbates Metabolic Derangement in Cardiac Hypertrophy and Heart Failure via PPARα Pathway. In Frontiers in cardiovascular medicine, 8, 722908. doi:10.3389/fcvm.2021.722908. https://pubmed.ncbi.nlm.nih.gov/34458345/