Adtrp-KO Mouse

Adtrp, short for Androgen-Dependent TFPI-Regulating Protein, is an androgen-inducible gene. It plays a crucial role in regulating the expression and activity of Tissue Factor Pathway Inhibitor (TFPI) on endothelial cells, which is involved in the coagulation pathway [1]. Additionally, Adtrp is a serine hydrolase that can hydrolyze fatty acid esters of hydroxy-fatty acids (FAHFAs), which have anti-diabetic and anti-inflammatory properties [1,2,4,5]. Single-nucleotide polymorphisms in Adtrp are associated with coronary artery disease, myocardial infarction, and deep vein thrombosis/venous thromboembolism, highlighting its importance in cardiovascular-related diseases [1].

In Adtrp knockout (KO) mice, there are multiple abnormalities in thermogenesis, metabolism, and maturation of brown/beige adipocytes, leading to excess lipid accumulation in brown adipose tissue and cold intolerance. Mechanistically, Adtrp binds to S100 calcium-binding protein b (S100b) to indirectly mediate its secretion, promoting β3-adrenergic receptor (β3-AR) mediated thermogenesis [3]. Tissues from Adtrp-KO mice had higher concentrations of FAHFAs, indicating that Adtrp controls FAHFA levels through hydrolysis [4].

In conclusion, Adtrp has diverse functions in various biological processes. Its role in regulating TFPI expression is associated with cardiovascular diseases, and its function in hydrolyzing FAHFAs and regulating adipose tissue thermogenesis is related to metabolic processes. The study of Adtrp KO mouse models has provided valuable insights into its functions in these specific disease-related biological processes, contributing to a better understanding of the underlying mechanisms in health and disease.

References:

1. Lupu, Cristina, Patel, Maulin M, Lupu, Florea. 2021. Insights into the Functional Role of ADTRP (Androgen-Dependent TFPI-Regulating Protein) in Health and Disease. In International journal of molecular sciences, 22, . doi:10.3390/ijms22094451. https://pubmed.ncbi.nlm.nih.gov/33923232/

2. Defour, Merel, van Weeghel, Michel, Hermans, Jill, Kersten, Sander. 2021. Hepatic ADTRP overexpression does not influence lipid and glucose metabolism. In American journal of physiology. Cell physiology, 321, C585-C595. doi:10.1152/ajpcell.00185.2021. https://pubmed.ncbi.nlm.nih.gov/34288722/

3. Li, Peng, Song, Runjie, Du, Yaqi, Liu, Huijiao, Li, Xiangdong. 2022. Adtrp regulates thermogenic activity of adipose tissue via mediating the secretion of S100b. In Cellular and molecular life sciences : CMLS, 79, 407. doi:10.1007/s00018-022-04441-9. https://pubmed.ncbi.nlm.nih.gov/35804197/

4. Erikci Ertunc, Meric, Kok, Bernard P, Parsons, William H, Saez, Enrique, Saghatelian, Alan. 2020. AIG1 and ADTRP are endogenous hydrolases of fatty acid esters of hydroxy fatty acids (FAHFAs) in mice. In The Journal of biological chemistry, 295, 5891-5905. doi:10.1074/jbc.RA119.012145. https://pubmed.ncbi.nlm.nih.gov/32152231/

5. Parsons, William H, Kolar, Matthew J, Kamat, Siddhesh S, Saghatelian, Alan, Cravatt, Benjamin F. 2016. AIG1 and ADTRP are atypical integral membrane hydrolases that degrade bioactive FAHFAs. In Nature chemical biology, 12, 367-372. doi:10.1038/nchembio.2051. https://pubmed.ncbi.nlm.nih.gov/27018888/