PUBLICATION
Zebrafish are resilient to the loss of major diacylglycerol acyltransferase enzymes
- Authors
- Wilson, M.H., Hensley, M.R., Shen, M.C., Lu, H.Y., Quinlivan, V.H., Busch-Nentwich, E.M., Rawls, J.F., Farber, S.A.
- ID
- ZDB-PUB-241114-41
- Date
- 2024
- Source
- The Journal of biological chemistry 300(12): 107973 (Journal)
- Registered Authors
- Busch-Nentwich, Elisabeth, Farber, Steven, Quinlivan-Repasi, Vanessa, Rawls, John F., Shen, Meng-Chieh, Wilson, Meredith
- Keywords
- acyltransferase, dgat, lipid droplet, lipoprotein secretion, membrane enzyme, mogat3, mutant, yolk syncytial layer, zebrafish
- Datasets
- GEO:GSE279170
- MeSH Terms
-
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- Lipid Droplets/metabolism
- Animals
- Yolk Sac/enzymology
- Yolk Sac/metabolism
- Diacylglycerol O-Acyltransferase*/genetics
- Diacylglycerol O-Acyltransferase*/metabolism
- Mutation
- Triglycerides*/biosynthesis
- Triglycerides*/metabolism
- Zebrafish*/genetics
- Zebrafish*/metabolism
- PubMed
- 39510175 Full text @ J. Biol. Chem.
Citation
Wilson, M.H., Hensley, M.R., Shen, M.C., Lu, H.Y., Quinlivan, V.H., Busch-Nentwich, E.M., Rawls, J.F., Farber, S.A. (2024) Zebrafish are resilient to the loss of major diacylglycerol acyltransferase enzymes. The Journal of biological chemistry. 300(12):107973.
Abstract
In zebrafish, maternally deposited yolk is the source of nutrients for embryogenesis prior to digestive system maturation. Yolk nutrients are processed and secreted to the growing organism by an extra-embryonic tissue, the yolk syncytial layer (YSL). Export of lipid from the YSL occurs through the production of triacylglycerol-rich lipoproteins. Here we report that mutations in the triacylglycerol synthesis enzyme, diacylglycerol acyltransferase-2 (Dgat2), cause yolk sac opacity due to aberrant accumulation of cytoplasmic lipid droplets in the YSL. Though triacylglycerol synthesis continues, it is not properly coupled to lipoprotein production as dgat2 mutants produce fewer, smaller, ApoB-containing lipoproteins. Unlike DGAT2-null mice, which are lipopenic and die soon after birth, zebrafish dgat2 mutants are viable, fertile and exhibit normal mass and adiposity. Residual Dgat activity cannot be explained by the activity of other known Dgat isoenzymes, as dgat1a;dgat1b;dgat2 triple mutants continue to produce YSL lipid droplets and remain viable as adults. Further, the newly identified diacylglycerol acyltransferase, Tmem68, is also not responsible for the residual triacylglycerol synthesis activity. Unlike overexpression of Dgat1a and Dgat1b, monoacylglycerol acyltransferase-3 (Mogat3b) overexpression does not rescue yolk opacity, suggesting it does not possess Dgat activity in the YSL. However, mogat3b;dgat2 double mutants exhibit increased yolk opacity and often have structural alterations of the yolk extension. Quadruple mogat3b;dgat1a;dgat1b;dgat2 mutants either have severely reduced viability and stunted growth, or do not survive past 3 days post fertilization, depending on the dgat2 mutant allele present. Our study highlights the remarkable ability of vertebrates to synthesize triacylglycerol through multiple biosynthetic pathways.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping