Apom-KO Mouse

ApoM, short for apolipoprotein M, is a member of the apolipoprotein family. It is primarily expressed and secreted from the liver and kidneys. ApoM serves as the main chaperone of sphingosine-1-phosphate (S1P), a small signalling molecule involved in numerous physiologic and pathophysiologic processes. Together, the apoM-S1P axis is associated with lipid metabolism, inflammation, endothelial cell permeability, and lipid turnover [1,2].

ApoM-deficient mice display an increased activity in brown adipose tissue and a concomitant fast turnover of triglycerides, suggesting that the apoM/S1P axis plays a significant role in maintaining a balanced triglyceride metabolism [5]. In type 1 diabetes, higher apoM levels at certain time-points in the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) cohort were associated with an increased risk of progression to macroalbuminuria (MA) and chronic kidney disease (CKD), indicating its role in the development of nephropathy [4]. In kidney renal clear cell carcinoma (KIRC), ApoM overexpression significantly inhibited cell proliferation in vitro, suppressed epithelial-mesenchymal transition (EMT), decreased metastatic capacity, and inhibited tumor growth in vivo, potentially through the Hippo-YAP signaling pathway [3].

In conclusion, ApoM is crucial for the transport of S1P and is involved in multiple biological processes. Studies using gene-knockout or other loss-of-function models have revealed its significance in lipid metabolism, diabetes-related kidney diseases, and KIRC. These findings provide insights into potential therapeutic targets for diseases associated with ApoM dysregulation.

References:

1. Chen, Zhiyang, Hu, Min. 2020. The apoM-S1P axis in hepatic diseases. In Clinica chimica acta; international journal of clinical chemistry, 511, 235-242. doi:10.1016/j.cca.2020.10.023. https://pubmed.ncbi.nlm.nih.gov/33096030/

2. Bisgaard, Line S, Christoffersen, Christina. 2021. The apoM/S1P Complex-A Mediator in Kidney Biology and Disease? In Frontiers in medicine, 8, 754490. doi:10.3389/fmed.2021.754490. https://pubmed.ncbi.nlm.nih.gov/34722589/

3. Xu, Ting, Wei, Dan, Yang, Zhe, Xu, Zhipeng, Wang, Jianning. 2023. ApoM suppresses kidney renal clear cell carcinoma growth and metastasis via the Hippo-YAP signaling pathway. In Archives of biochemistry and biophysics, 743, 109642. doi:10.1016/j.abb.2023.109642. https://pubmed.ncbi.nlm.nih.gov/37211224/

4. Baker, Nathaniel L, Hammad, Samar M, Hunt, Kelly J, Klein, Richard L, Lopes-Virella, Maria F. . Plasma apoM Levels and Progression to Kidney Dysfunction in Patients With Type 1 Diabetes. In Diabetes, 71, 1795-1799. doi:10.2337/db21-0920. https://pubmed.ncbi.nlm.nih.gov/35554520/

5. Hajny, Stefan, Borup, Anna, Elsøe, Sara, Christoffersen, Christina. 2021. Increased plasma apoM levels impair triglyceride turnover in mice. In Biochimica et biophysica acta. Molecular and cell biology of lipids, 1866, 158969. doi:10.1016/j.bbalip.2021.158969. https://pubmed.ncbi.nlm.nih.gov/34051379/