Fabp2-KO Mouse

Fabp2, also known as intestinal fatty acid binding protein (I-FABP), is a key protein in lipid transport. Specifically expressed in the small intestine, it traffics lipids from the intestinal lumen to enterocytes and binds excess fatty acids to maintain a stable fatty acid pool in the epithelium. It is also involved in carrying lipophilic drugs for targeted transport. When the intestinal epithelium is disrupted, it is released into the circulation, making it a potential biomarker [2].

In mouse models, the transcription factors HNF4A and HNF4G directly activate Fabp2 along with other genes required for fatty acid oxidation (FAO). Double-knockout of HNF4A and HNF4G in mice led to a significant decrease in Fabp2 expression levels, FAO activity, and TCA cycle metabolites, indicating that Fabp2 is crucial for the renewal of intestinal stem cells (ISCs) as FAO supports ISC renewal [4].

In conclusion, Fabp2 is essential for lipid metabolism in the intestine and plays a key role in the renewal of intestinal stem cells as revealed through mouse model-based research. Its study also has implications in understanding diseases such as diabetes, where its levels are associated with diabetic nephropathy [3], and synucleinopathies, where it may contribute to the pathogenesis and progression of the disease [1].

References:

1. Sekimori, Tomoki, Fukunaga, Kohji, Oizumi, Hideki, Sasaki, Takuya, Kawahata, Ichiro. . FABP2 is Involved in Intestinal α-Synuclein Pathologies. In Journal of integrative neuroscience, 23, 44. doi:10.31083/j.jin2302044. https://pubmed.ncbi.nlm.nih.gov/38419457/

2. Huang, Xi, Zhou, Youci, Sun, Yunwei, Wang, Qijun. 2022. Intestinal fatty acid binding protein: A rising therapeutic target in lipid metabolism. In Progress in lipid research, 87, 101178. doi:10.1016/j.plipres.2022.101178. https://pubmed.ncbi.nlm.nih.gov/35780915/

3. Tsai, I-Ting, Wu, Cheng-Ching, Hung, Wei-Chin, Lee, Yau-Jiunn, Wang, Chao-Ping. 2020. FABP1 and FABP2 as markers of diabetic nephropathy. In International journal of medical sciences, 17, 2338-2345. doi:10.7150/ijms.49078. https://pubmed.ncbi.nlm.nih.gov/32922199/

4. Chen, Lei, Vasoya, Roshan P, Toke, Natalie H, Su, Xiaoyang, Verzi, Michael P. 2019. HNF4 Regulates Fatty Acid Oxidation and Is Required for Renewal of Intestinal Stem Cells in Mice. In Gastroenterology, 158, 985-999.e9. doi:10.1053/j.gastro.2019.11.031. https://pubmed.ncbi.nlm.nih.gov/31759926/