Dataset Information

Transcript variants of long-chain acyl-CoA synthase 1 have distinct roles in sheep lipid metabolism

ABSTRACT: Mutton has recently been identified to be a consumer favorite, and intermuscular fat is the key factor in determining meat tenderness. Long-chain acyl-CoA synthetase 1 (ACSL1) is a vital subtype of the ACSL family that is involved in the synthesis of lipids from acyl-CoA and the oxidation of fatty acids. The amplification of the ACSL1 gene using rapid amplification of cDNA ends revealed that the alternative polyadenylation (APA) results in two transcripts of the ACSL1 gene. Exon 18 had premature termination, resulting in a shorter CDS region. In this study, the existence of two transcripts of varying lengths translated normally and designated ACSL1-a and ACSL1-b was confirmed. Overexpression of ACSL1-a can promote the synthesis of an intracellular diglyceride, while ACSL1-b can promote triglyceride synthesis. The transfection of ACSL1 shRNA knocks down both the transcripts, the triglyceride content was significantly reduced after differentiation and induction; and lipidome sequencing results exhibited a significant decrease in 14-22 carbon triglyceride metabolites. The results of the present study indicated that the ACSL1 gene played a crucial role in the synthesis of triglycerides. Furthermore, the two transcripts involved in various interactions in the triglyceride synthesis process may be the topic of interest for future research and provide a more theoretical basis for sheep breeding.

INSTRUMENT(S): Liquid Chromatography MS - positive, Liquid Chromatography MS - negative

SUBMITTER: Yang Cao

PROVIDER: MTBLS5808 | MetaboLights | 2023-02-06

REPOSITORIES: MetaboLights

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Transcript variants of long-chain acyl-CoA synthase 1 have distinct roles in sheep lipid metabolism.

Cao Yang Y Yu Yongsheng Y Zhang Lichun L Liu Yu Y Zheng Kaizhi K Wang Sutian S Jin Haiguo H Liu Lixiang L Cao Yang Y

Frontiers in genetics 20221122

Mutton has recently been identified to be a consumer favorite, and intermuscular fat is the key factor in determining meat tenderness. Long-chain acyl-CoA synthetase 1 (ACSL1) is a vital subtype of the ACSL family that is involved in the synthesis of lipids from acyl-CoA and the oxidation of fatty acids. The amplification of the ACSL1 gene using rapid amplification of cDNA ends revealed that the alternative polyadenylation (APA) results in two transcripts of the ACSL1 gene. Exon 18 had premature ...[more]

PMID: 36482895

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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.

Project description:Fatty acid synthesis is closely linked to nutrient availability and cellular energetic status. The committed step in fatty acid synthesis is the acetyl CoA carboxylase. Eukaryotes have two genes encoding acetyl CoA carboxylases, one encoding a cytosolic enzyme and another coding for a mitochondrial enzyme. They catalyze the synthesis of malonyl CoA in the cytosol and the mitochondria, respectively. While cytosolic malonyl CoA is the precursor for fatty acid synthesis, mitochondrial malonyl CoA controls the transfer of fatty acyl group into the mitochondria by inhibiting carnitine/palmitoyl transferase activity and thus, regulates Î²-oxidation. In Saccharomyces cerevisiae, Î²-oxidation is restricted to the peroxisomes, raising the question of the function of the mitochondrial isoform (HFA1). In this study, we replaced the cytosolic Acc1 with Hfa1 expressed in the cytosol by removing the mitochondrial leader peptide, under control of the HFA1 promoter. We studied fatty acid synthesis and transcription profiles in this strain during starvation for carbon or nitrogen, using glucose or ethanol as the carbon source. Under all the conditions studied, the key sensor of energetic status, Snf1, was activated, indicating active inhibition of fatty acid synthesis. The pool size of fatty acids was smaller when Acc1 was replaced with truncated Hfa1 for fatty acid synthesis. Yet, the transcription profiles were similar in both the cases. These results point towards the conclusion that Hfa1 is either catalytically less efficient or it is more sensitive to inhibition by Snf1. Gene expression from a strain of Saccharomyces cerevisiae where cytosolic fatty acid synthesis occurs by mitochondrial acetyl CoA carboxylase (without its mitochondrial leader peptide) is compared with that in a reference strain while growing in chemostats on carbon or nitrogen starvation using glucose or ethanol as the carbon source. There are two strains (reference or mutant), two carbon sources (glucose or ethanol) and two limitations (carbon or nitrogen), resulting in 8 comparisons. Each array was performed in duplicate, resulting in 16 CEL files. Growth was limited by either carbon or nitrogen. When carbon was the limited nutrient, we tested growth on either glucose or ethanol (both using ammonium sulfate as the nitrogen source). When ammonium sulfate was limiting, we used either glucose or ethanol as the carbon source.

Dataset Information

Transcript variants of long-chain acyl-CoA synthase 1 have distinct roles in sheep lipid metabolism

Publications

Transcript variants of long-chain acyl-CoA synthase 1 have distinct roles in sheep lipid metabolism.

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