Inhibition of Mammalian Target of Rapamycin Complex 1 (mTORC1) Downregulates ELOVL1 Gene Expression and Fatty Acid Synthesis in Goat Fetal Fibroblasts

Wang, Weipeng; He, Qiburi; Guo, Zhixin; Yang, Limin; Bao, Lili; Bao, Wenlei; Xu, Zheng; Wang, Yanfeng; Wang, Zhigang

doi:10.3390/ijms160716440

Cited by 12 publications

(8 citation statements)

References 29 publications

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“…ELOVL1 , a widely expressed gene in tissues from the ELOVL family, encoded the fatty acid elongase to produce C20–C28 fatty acids. In this study, ELOVL1 was observably upregulated in chicken jejuna from LPC-treated groups, consistent with the report that ELOVL1 regulated the very-long-chain fatty acid and sphingolipids synthesis, and was closely associated with the intestinal barrier function ( 22 , 23 ). ELOVL1 expression induced by inhibiting mTOR1 decreased fatty acids synthesis ( 22 , 23 ).…”

Section: Discussionsupporting

confidence: 92%

“…In this study, ELOVL1 was observably upregulated in chicken jejuna from LPC-treated groups, consistent with the report that ELOVL1 regulated the very-long-chain fatty acid and sphingolipids synthesis, and was closely associated with the intestinal barrier function ( 22 , 23 ). ELOVL1 expression induced by inhibiting mTOR1 decreased fatty acids synthesis ( 22 , 23 ). A previous study in mice indicated that ELOVL1 knockout induced the defects in the epidermal barrier and the death after birth.…”

Section: Discussionsupporting

confidence: 92%

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Mechanism of Lysoforte in Improving Jejuna Morphology and Health in Broiler Chickens

Shi²,

Mesalam³

et al. 2022

Front. Vet. Sci.

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Lysoforte (LFT) plays a vital role in maintaining broilers' health and intestinal morphology. However, the mechanism behind the effects of LFT improving intestinal morphology and health is still unclear. Therefore, this study was implemented to explore the central genes linked to the regulatory effect of LFT. Seventy-five newly hatched Cobb 500 male broilers were randomly divided into three groups: control, LFT500, and LFT1000 groups, with 25 chicks per group. The control chicks were provided with the basal diet, and the birds in LFT500 and LFT1000 groups were offered the same basal diet with 500 g/ton and 1,000 g/ton LFT, respectively. GSE94622 dataset consisted of the control and two LFT-treated groups (LFT500 and LFT1000). Jejuna samples were obtained from Gene Expression Omnibus (GEO). Totally 106–344 DEGs were obtained by comparing LFT500 and LFT1000 vs. control and LFT1000 vs. LFT500. Gene ontology (GO) enrichment suggested that the DEGs are mainly related to the phosphatidylethanolamine biosynthetic process and neuron projection extension. KEGG analysis suggested the DEGs were enriched in AGE-RAGE, fatty acid elongation, ECM-receptor interaction (ECMRI), glycerophospholipid metabolism, focal adhesion, unsaturated fatty acids biosynthesis, and ABC transporters. Moreover, 29 genes, such as REG4, GJB1, KAT2A, APOA5, SERPINE2, ELOVL1, ABCC2, ANKRD9, CYP4V2, and PISD, might be closely related to promoting jejuna morphology in broilers. Taken together, our observation enhances the understanding of LFT in maintaining intestinal architecture and the general health of broiler chickens.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 92%

Mechanism of Lysoforte in Improving Jejuna Morphology and Health in Broiler Chickens

Shi²,

Mesalam³

et al. 2022

Front. Vet. Sci.

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“…The analysis of ELOVL1 homologues from different organisms showed that p.Ser165 is highly conserved being present in all the analysed species (n=80, figure 3D). The p.Ser165Phe mutation is located in the region that may undergo myristoylation7 (figure 3D), although experimental data are necessary to verify this prediction.…”

Section: Resultsmentioning

confidence: 98%

Dominant ELOVL1 mutation causes neurological disorder with ichthyotic keratoderma, spasticity, hypomyelination and dysmorphic features

Kutkowska-Kaźmierczak¹,

Rydzanicz

Chlebowski

et al. 2018

J Med Genet

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“…It is known that lipid synthesis and myelin formation is under the control of mTORC1 signaling [157,158,159]. It is particularly noteworthy here that Elovl1 expression is downregulated upon inhibition of mTORC1, and the medium-chain fatty acid availability acts via mTORC1 signaling to trigger Elovl5 and Elovl6 expression [160,161,162,163]. Given that ataxin-2 orthologs in yeast, nematodes, and mice were shown to play a conserved role as inhibitors of mTORC1 signaling and growth [36,48,164,165,166], the broad repression of Elovl1/4/5/6 in cerebellum and spinal cord as well as the repression of Elovl2/7 in cerebellum may be a very sensitive and specific reflection of this ancient control of ATXN2 over lipid metabolism.…”

Section: Discussionmentioning

confidence: 99%

In Human and Mouse Spino-Cerebellar Tissue, Ataxin-2 Expansion Affects Ceramide-Sphingomyelin Metabolism

Sen

Arsovic

Meierhofer

et al. 2019

IJMS

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Ataxin-2 (human gene symbol ATXN2) acts during stress responses, modulating mRNA translation and nutrient metabolism. Ataxin-2 knockout mice exhibit progressive obesity, dyslipidemia, and insulin resistance. Conversely, the progressive ATXN2 gain of function due to the fact of polyglutamine (polyQ) expansions leads to a dominantly inherited neurodegenerative process named spinocerebellar ataxia type 2 (SCA2) with early adipose tissue loss and late muscle atrophy. We tried to understand lipid dysregulation in a SCA2 patient brain and in an authentic mouse model. Thin layer chromatography of a patient cerebellum was compared to the lipid metabolome of Atxn2-CAG100-Knockin (KIN) mouse spinocerebellar tissue. The human pathology caused deficits of sulfatide, galactosylceramide, cholesterol, C22/24-sphingomyelin, and gangliosides GM1a/GD1b despite quite normal levels of C18-sphingomyelin. Cerebellum and spinal cord from the KIN mouse showed a consistent decrease of various ceramides with a significant elevation of sphingosine in the more severely affected spinal cord. Deficiency of C24/26-sphingomyelins contrasted with excess C18/20-sphingomyelin. Spinocerebellar expression profiling revealed consistent reductions of CERS protein isoforms, Sptlc2 and Smpd3, but upregulation of Cers2 mRNA, as prominent anomalies in the ceramide–sphingosine metabolism. Reduction of Asah2 mRNA correlated to deficient S1P levels. In addition, downregulations for the elongase Elovl1, Elovl4, Elovl5 mRNAs and ELOVL4 protein explain the deficit of very long-chain sphingomyelin. Reduced ASMase protein levels correlated to the accumulation of long-chain sphingomyelin. Overall, a deficit of myelin lipids was prominent in SCA2 nervous tissue at prefinal stage and not compensated by transcriptional adaptation of several metabolic enzymes. Myelination is controlled by mTORC1 signals; thus, our human and murine observations are in agreement with the known role of ATXN2 yeast, nematode, and mouse orthologs as mTORC1 inhibitors and autophagy promoters.

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Inhibition of Mammalian Target of Rapamycin Complex 1 (mTORC1) Downregulates ELOVL1 Gene Expression and Fatty Acid Synthesis in Goat Fetal Fibroblasts

Cited by 12 publications

References 29 publications

Mechanism of Lysoforte in Improving Jejuna Morphology and Health in Broiler Chickens

Mechanism of Lysoforte in Improving Jejuna Morphology and Health in Broiler Chickens

Dominant ELOVL1 mutation causes neurological disorder with ichthyotic keratoderma, spasticity, hypomyelination and dysmorphic features

In Human and Mouse Spino-Cerebellar Tissue, Ataxin-2 Expansion Affects Ceramide-Sphingomyelin Metabolism

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