Dataset Information

Rapamycin Inhibits Expression of Elongation of Very-long-chain Fatty Acids 1 and Synthesis of Docosahexaenoic Acid in Bovine Mammary Epithelial Cells.

ABSTRACT: Mammalian target of rapamycin complex 1 (mTORC1) is a central regulator of cell growth and metabolism and is sufficient to induce specific metabolic processes, including de novo lipid biosynthesis. Elongation of very-long-chain fatty acids 1 (ELOVL1) is a ubiquitously expressed gene and the product of which was thought to be associated with elongation of carbon (C) chain in fatty acids. In the present study, we examined the effects of rapamycin, a specific inhibitor of mTORC1, on ELOVL1 expression and docosahexaenoic acid (DHA, C22:6 n-3) synthesis in bovine mammary epithelial cells (BMECs). We found that rapamycin decreased the relative abundance of ELOVL1 mRNA, ELOVL1 expression and the level of DHA in a time-dependent manner. These data indicate that ELOVL1 expression and DHA synthesis are regulated by mTORC1 in BMECs.

SUBMITTER: Guo Z

PROVIDER: S-EPMC5088386 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Rapamycin Inhibits Expression of Elongation of Very-long-chain Fatty Acids 1 and Synthesis of Docosahexaenoic Acid in Bovine Mammary Epithelial Cells.

Guo Zhixin Z Wang Yanfeng Y Feng Xue X Bao Chaogetu C He Qiburi Q Bao Lili L Hao Huifang H Wang Zhigang Z

Asian-Australasian journal of animal sciences 20160118 11

Mammalian target of rapamycin complex 1 (mTORC1) is a central regulator of cell growth and metabolism and is sufficient to induce specific metabolic processes, including <i>de novo</i> lipid biosynthesis. Elongation of very-long-chain fatty acids 1 (<i>ELOVL1</i>) is a ubiquitously expressed gene and the product of which was thought to be associated with elongation of carbon (C) chain in fatty acids. In the present study, we examined the effects of rapamycin, a specific inhibitor of mTORC1, on E ...[more]

PMID: 26954224

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Project description:BackgroundTriple-negative breast cancer (TN) is more aggressive than other subtypes of breast cancer and has a lower survival rate. Furthermore, detailed biological information about the disease is lacking. This study investigated characteristics of metabolic pathways in TN.MethodsWe performed the metabolome analysis of 74 breast cancer tissues and the corresponding normal breast tissues using LC/MS. Furthermore, we classified the breast cancer tissues into ER-positive, PgR-positive, HER2-negative breast cancer (EP+H-) and TN, and then the differences in their metabolic pathways were investigated. The RT-PCR and immunostaining were carried out to examine the expression of ELOVL1, 2, 3, 4, 5, 6, and 7.ResultsWe identified 142 of hydrophilic metabolites and 278 of hydrophobic lipid metabolites in breast tissues. We found the differences between breast cancer and normal breast tissues in choline metabolism, glutamine metabolism, lipid metabolism, and so on. Most characteristic of comparison between EP+H- and TN were differences in fatty acid metabolism was which were related to the elongation of very long chain fatty acids were detected between TN and EP+H-. Real-time RT-PCR showed that the mRNA expression levels of ELOVL1, 5, and 6 were significantly upregulated by 8.5-, 4.6- and 7.0-fold, respectively, in the TN tumors compared with their levels in the corresponding normal breast tissue samples. Similarly, the mRNA expression levels of ELOVL1, 5, and 6 were also significantly higher in the EP+H- tissues than in the corresponding normal breast tissues (by 4.9-, 3.4-, and 2.1-fold, respectively). The mRNA expression level of ELOVL6 was 2.6-fold higher in the TN tumors than in the EP+H- tumors. During immunostaining, the TN and EP+H- tumors demonstrated stronger ELOVL1 and 6 staining than the corresponding normal breast tissues, but ELOVL5 was not stained strongly in the TN or EP+H- tumors. Furthermore, the TN tumors exhibited stronger ELOVL1 and 6 staining than the EP+H- tumors.ConclusionsMarked differences in fatty acid metabolism pathways, including those related to ELOVL1 and 6, were detected between TN and EP+H-, and it was suggested that ELOVL1 and 6-related fatty acid metabolism pathways may be targets for therapies against TN.

Project description:Elongation of the Very-Long-Chain Fatty Acids-4 (ELOVL4) enzyme that is expressed in neuronal tissues, sperm, and testes mediates biosynthesis of very-long-chain polyunsaturated fatty acids (VLC-PUFAs) from dietary long chain PUFAs (LC-PUFAs). The VLC-PUFAs are critical for neuronal and reproductive function. Therefore, mutations in ELOVL4 that affect VLC-PUFA biosynthesis contribute to retinal degenerative diseases including Autosomal Dominant Stargardt-like Macular Dystrophy (STGD3). Recent studies have also shown not only a depletion of retinal VLC-PUFAs with normal aging but also a more significant loss of VLC-PUFAs in donor eyes of patients with age-related macular degeneration (AMD). However, currently, there are no natural sources of VLC-PUFAs to be evaluated as dietary supplements for the attenuation of retinal degeneration in animal models of STGD3. Here, we report the development of a novel chemical approach for elongation of eicosapentaenoic (C20:5 n-3) and docosahexaenoic (C22:6 n-3) acids from fish oils by 6 carbon atoms to make a unique group of VLC-PUFAs, namely all-cis-hexacosa-11,14,17,20,23-pentaenoic acids (C26:5 n-3) and all-cis-octacosa-10,13,16,19,22,25-hexaenoic acids (C28:6 n-3). The three-step elongation approach that we report herein resulted in a good overall yield of up to 20.2%. This more sustainable approach also resulted in improved functional group compatibility and minimal impact on the geometrical integrity of the all-cis double bond system of the VLC-PUFAs. In addition, we also successfully used commercial deep-sea fish oil concentrate as an inexpensive material for the C6 elongation of fish oil LC-PUFAs into VLC-PUFAs, which resulted in the making of gram scales of VLC-PUFAs with an even higher isolation yield of 31.0%. The quality of fish oils and the content of oxidized lipids were key since both strongly affected the activity of the PEPPSI-IPr catalyst and ultimately the yield of coupling reactions. Downstream enzymatic interesterification was used for the first time to prepare structured glycerolipids enriched with VLC-PUFAs that could be evaluated in vivo to determine absorption and transport to target tissues relative to those of the free fatty acid forms. It turned out that in the synthesis of structured triacylglycerols and glycerophospholipids with VLC-PUFAs, the polarity of the immobilized lipase carrier and its humidity were essential.

Dataset Information

Rapamycin Inhibits Expression of Elongation of Very-long-chain Fatty Acids 1 and Synthesis of Docosahexaenoic Acid in Bovine Mammary Epithelial Cells.

Publications

Rapamycin Inhibits Expression of Elongation of Very-long-chain Fatty Acids 1 and Synthesis of Docosahexaenoic Acid in Bovine Mammary Epithelial Cells.

Similar Datasets

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