Apob-KO Mouse

Apob, short for apolipoprotein B, is a key protein in the biosynthesis and metabolism of triglyceride-rich lipoproteins (TRLs), such as very-low-density lipoprotein (VLDL) and chylomicron. It plays a crucial role in the intracellular assembly, trafficking, degradation, and secretion of these lipoproteins, thus having a significant impact on cardiovascular health [1]. Zebrafish, a powerful model for mammalian lipoprotein metabolism, have been used to study Apob-containing lipoprotein metabolism. Mutations in zebrafish genes related to lipoprotein formation, including those affecting Apob, lead to visible phenotypes like cytoplasmic lipid droplet accumulation and opaque yolk, facilitating the investigation of lipoprotein pathway disturbances [2].

There is a high correlation between apolipoprotein B (apoB) and non-high-density lipoprotein cholesterol (non-HDL-C), but they are not clinical equivalents as there are cases where the two yield different clinical information, potentially changing diagnosis and therapy decisions [3]. APOB has also been identified as a mediator in the protective effect of SGLT2 inhibition against myocardial infarction, suggesting its role in this cardiovascular-related process [4]. In the PROMINENT trial, changes in apolipoprotein B, along with remnant cholesterol and LDL cholesterol, helped explain the trial's results, with an increase in apolipoprotein B being associated with a trend toward more atherosclerotic cardiovascular disease (ASCVD) [5].

In summary, Apob is essential for the metabolism of TRLs, and its study using models like zebrafish provides insights into lipoprotein metabolism. Research on Apob has significant implications for understanding and managing cardiovascular-related diseases, as it is associated with various aspects of lipid metabolism and disease outcomes.

References:

1. Borén, Jan, Taskinen, Marja-Riitta, Packard, Chris J. 2024. Biosynthesis and Metabolism of ApoB-Containing Lipoproteins. In Annual review of nutrition, 44, 179-204. doi:10.1146/annurev-nutr-062222-020716. https://pubmed.ncbi.nlm.nih.gov/38635875/

2. Moll, Tabea O C, Farber, Steven A. 2024. Zebrafish ApoB-Containing Lipoprotein Metabolism: A Closer Look. In Arteriosclerosis, thrombosis, and vascular biology, 44, 1053-1064. doi:10.1161/ATVBAHA.123.318287. https://pubmed.ncbi.nlm.nih.gov/38482694/

3. Sniderman, Allan, Williams, Ken, Cobbaert, Christa. . ApoB versus non-HDL-C: what to do when they disagree. In Current atherosclerosis reports, 11, 358-63. doi:. https://pubmed.ncbi.nlm.nih.gov/19664379/

4. Shi, Lili, Li, Gen, Hou, Ningxin, Luo, Jinlan, Hu, Shuiqing. 2024. APOB and CCL17 as mediators in the protective effect of SGLT2 inhibition against myocardial infarction: Insights from proteome-wide mendelian randomization. In European journal of pharmacology, 976, 176619. doi:10.1016/j.ejphar.2024.176619. https://pubmed.ncbi.nlm.nih.gov/38679119/

5. Doi, Takahito, Langsted, Anne, Nordestgaard, Børge G. 2024. Remnant cholesterol, LDL cholesterol, and apoB absolute mass changes explain results of the PROMINENT trial. In Atherosclerosis, 393, 117556. doi:10.1016/j.atherosclerosis.2024.117556. https://pubmed.ncbi.nlm.nih.gov/38678642/