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Zebrafish are resilient to the loss of major diacylglycerol acyltransferase enzymes

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.

ORGANISM(S): Danio rerio

PROVIDER: GSE279170 | GEO | 2024/11/07

REPOSITORIES: GEO

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Project description:<h4>Background: </h4> The study of fat deposition in yaks of different gender plays a positive role in improving the meat quality and breeding of yaks. In this work, the characteristic of fat deposition in male and female yaks, and the regulations of gender difference to fat deposition in yaks were explored. <h4>Result: </h4> Compared with male yaks, the female yaks possessed higher or more body fat rate (BFR) of visceral except liver, fat content in muscle and liver and subcutaneous fat ( p < 0.05); the cholesterol (CH), triglyceride (TG), very low-density lipoprotein (VLDL), leptin (LEP) and cortisol (COR) in serum of female yaks were higher ( p < 0.05 ); meanwhile, the fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), stearoyl-CoA desaturase (SCD) and diacylglycerol acyltransferase 1 (DGAT-1) in livers of female yaks were higher ( p < 0.05). The metabonomics analysis showed 13(S)-HODE, linoleic acid and linolenic acid and myo-inositol in subcutaneous fat of female yaks increased ( p < 0.05 ); meanwhile, the transcriptomic analysis the gene expressions of prenylcysteine oxidase 1 (PCYOX1), acyl-coenzyme a-cholesterol acyltransferase (ACAT), protein farnesyltransferase subunit beta (FNTB), apolipoprotein E (ApoE), DGAT2, very long chain fatty acids protein 6 (ELOVL6), NADP-dependent malic enzyme (ME1), SCD, acyl-CoA-binding protein (ACBP) and perilipin-5 (PLIN5), LEP, sterol regulatory element-binding protein 1 (SREBF1) upregulated in subcutaneous fat of female yaks ( p FDR < 0.05), whereas the gene expressions of CPT1, acetyl-CoA acyltransferase 1(ACAA1) and adipose triglyceride lipase (ATGL) downregulated ( p FD R < 0.01). <h4>Conclusion: </h4> The fat and cholesterol synthesis increased in liver of female yaks, and the fat transport in blood of female yaks increased too. In subcutaneous fat of female yaks, the high levels of myo-inositol activated the calcium signaling, following the increase of secretion in fat cell. Then, the high levels of LEP and 13(S)-HODE strengthened PPAR signal, and the fat synthesis, cholesterol synthesis, fatty acid biosynthesis of the linoleic and linolenic acid being the precursor increased, whereas lipolysis and fatty acid oxidation decreased by the regulation of downstream genes in PPAR signal. Meanwhile, SREBF1 also played an important part in the regulation of fat metabolism in yaks of different gender.

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Zebrafish are resilient to the loss of major diacylglycerol acyltransferase enzymes

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