Csad, or cysteine sulfinic acid decarboxylase, is a key enzyme in taurine biosynthesis. It converts cysteine sulfinic acid to hypotaurine, which is further processed to taurine. Taurine is involved in multiple physiological processes such as bile acid conjugation, plasma glucose regulation, and membrane stabilization [4,5]. Genetic models, like knockout mice, are valuable for studying Csad's functions.

In NAFLD research, Csad was found to be significantly decreased in patients, and this was confirmed in multiple NAFLD mouse models. AAV-mediated liver-directed gene overexpression of Csad in HFD-fed mice alleviated NAFLD-associated pathologies, increased genes related to fatty acid β-oxidation, and improved mitochondrial injury. The effect on lipid accumulation might be independent of the taurine pathway, suggesting Csad as a potential new drug target for NAFLD [1]. In CSAD-KO mice, there were alterations in glucose homeostasis, with slightly hypoglycemic levels and reduced plasma glucose post-injection compared to wild-type mice. Also, retinas without taurine supplementation showed substantial degeneration, which was rectified by taurine supplementation [2]. In two taurine-deficient mouse models (including CSAD-/-mice), CSAD knockout exacerbated DSS-induced colitis symptoms, intestinal barrier dysfunction, and the colonic mucosal inflammatory response [3].

In conclusion, Csad plays essential roles in maintaining taurine levels and is involved in important physiological functions. Research using Csad KO mouse models has revealed its significance in diseases such as NAFLD, glucose homeostasis-related disorders, and colitis, providing insights into potential therapeutic strategies for these conditions.

References:

1. Tan, Rongrong, Li, Jiayang, Liu, Lu, Gong, Likun, Ren, Jin. 2022. CSAD Ameliorates Lipid Accumulation in High-Fat Diet-Fed Mice. In International journal of molecular sciences, 23, . doi:10.3390/ijms232415931. https://pubmed.ncbi.nlm.nih.gov/36555571/

2. Sidime, Francoise, Phillips, Greg, LaMassa, Nicole, Park, Eunkyue, El Idrissi, Abdeslem. . Glucose Homeostasis and Retinal Histopathology in CSAD KO Mice. In Advances in experimental medicine and biology, 975 Pt 1, 503-511. doi:10.1007/978-94-024-1079-2_40. https://pubmed.ncbi.nlm.nih.gov/28849478/

3. Zheng, Jiaming, Zhang, Jinglin, Zhou, Yewen, Li, Bin, Cui, Sheng. 2024. Taurine Alleviates Experimental Colitis by Enhancing Intestinal Barrier Function and Inhibiting Inflammatory Response through TLR4/NF-κB Signaling. In Journal of agricultural and food chemistry, 72, 12119-12129. doi:10.1021/acs.jafc.4c00662. https://pubmed.ncbi.nlm.nih.gov/38761152/

4. Wang, Yifeng, Matye, David, Nguyen, Nga, Zhang, Yuxia, Li, Tiangang. 2018. HNF4α Regulates CSAD to Couple Hepatic Taurine Production to Bile Acid Synthesis in Mice. In Gene expression, 18, 187-196. doi:10.3727/105221618X15277685544442. https://pubmed.ncbi.nlm.nih.gov/29871716/

5. El Idrissi, Abdeslem. . Taurine Regulation of Neuroendocrine Function. In Advances in experimental medicine and biology, 1155, 977-985. doi:10.1007/978-981-13-8023-5_81. https://pubmed.ncbi.nlm.nih.gov/31468461/