Loss of asgr1a leads to the secretion of excess dietary cholesterol in zebrafish
Moll, T. O. C.; Derrick, J. T.; Sweeney, D. W.; Shin, J.; Farber, S. A.
Show abstract
One of the major pathways to clear glycoproteins from circulation is via the liver-specific asialoglycoprotein receptor (ASGPR). Loss of asialoglycoprotein receptor 1 (ASGR1), the major subunit of ASGPR, was recently found to correlate with lower levels of plasma apolipoprotein B- containing lipoproteins (B-lps) and a profoundly reduced risk of cardiovascular disease in humans. We set out to identify the zebrafish ortholog of ASGR1 (asgr1a) and generated two independent mutations in asgr1a using CRISPR/Cas9. Neither asgr1a mutation displayed changes in larval, juvenile, and adult B-lp numbers or sizes. However, when challenged with a Western diet, asgr1a mutant zebrafish exhibit less hepatic steatosis and lower hepatic triglyceride levels compared to control animals. Instead, the excess dietary cholesterol was excreted. While these results do not explain the cardioprotective nature of ASGR1 in humans, they indicate the importance of ASGR1 in modulating whole animal cholesterol flux.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Creation of a novel zebrafish model with low DHA status to study the role of maternal nutrition during neurodevelopment 95%
- Hepatocytes deficient in nuclear envelope protein lamina-associated polypeptide 1 are an ideal mammalian system to study intranuclear lipid droplets 94%
- Transgelin: A New Gene Involved in LDL Endocytosis Identified by a Genome-wide CRISPR-Cas9 Screen 94%
Similar papers in this journal
- The human glucocorticoid receptor variant rs6190 promotes blood cholesterol and atherosclerosis 95%
- Liver-specific suppression of ANGPTL4 improves obesity-associated diabetes and mitigates atherosclerosis in mice 94%
- ACVR1 antibodies exacerbate heterotopic ossification in fibrodysplasia ossificans progressiva (FOP) by activating FOP-mutant ACVR1 93%
Similar papers in this journal
- Comparative transcriptomics of lateral hypothalamic cell types reveals conserved growth hormone-tachykinin dynamics in feeding 95%
- Loss of Carnitine Palmitoyltransferase 1a Reduces Docosahexaenoic Acid-Containing Phospholipids and Drives Sexually Dimorphic Liver Disease in Mice 94%
- Hypoxia-inducible lipid droplet-associated interacts with DGAT1 and promotes lipid storage in hepatocytes 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.