Protein concentrations and activities of fatty acid desaturase and elongase enzymes in liver, brain, testicle, and kidney from mice: Substrate dependency.
elongase 2
elongase 5
enzymatic activity
polyunsaturated fatty acids
protein concentration
Δ-5 desaturase
Δ-6 desaturase
Journal
BioFactors (Oxford, England)
ISSN: 1872-8081
Titre abrégé: Biofactors
Pays: Netherlands
ID NLM: 8807441
Informations de publication
Date de publication:
20 Jul 2023
20 Jul 2023
Historique:
received:
07
02
2023
accepted:
04
07
2023
medline:
20
7
2023
pubmed:
20
7
2023
entrez:
20
7
2023
Statut:
aheadofprint
Résumé
The synthesis rates of n-3 and n-6 polyunsaturated fatty acids (PUFAs) in rodents and humans are not agreed upon and depend on substrate availability independently of the capacity for synthesis. Therefore, we aimed to assess the activities of the enzymes for n-3 and n-6 PUFA synthesis pathways in liver, brain, testicle, kidney, heart, and lung, in relation to their protein concentration levels. Eight-week-old Balb/c mice (n = 8) were fed a standard chow diet (6.2% fat, 18.6% protein, and 44.2% carbohydrates) until 14 weeks of age, anesthetized with isoflurane and tissue samples were collected (previously perfused) and stored at -80°C. The protein concentration of the enzymes (Δ-6D, Δ-5D, Elovl2, and Elovl5) were assessed by ELISA kits; their activities were assayed using specific PUFA precursors and measuring the respective PUFA products as fatty acid methyl esters by gas chromatographic analysis. The liver had the highest capacity for PUFA biosynthesis, with limited activity in the brain, testicles, and kidney, while we failed to detect activity in the heart and lung. The protein concentration and activity of the enzymes were significantly correlated. Furthermore, Δ-6D, Δ-5D, and Elovl2 have a higher affinity for n-3 PUFA precursors compared to n-6 PUFA. The capacity for PUFA synthesis in mice mainly resides in the liver, with enzymes having preference for n-3 PUFAs.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Fondo Nacional de Desarrollo Científico y Tecnológico
ID : 1221098
Informations de copyright
© 2023 International Union of Biochemistry and Molecular Biology.
Références
Hodson L, Gunn PJ. The regulation of hepatic fatty acid synthesis and partitioning: effect of nutritional state. Nat Rev Endocrinol. 2019;15:689-700.
Valenzuela R, Videla LA. Impact of the co-administration of n-3 fatty acids and olive oil components in preclinical nonalcoholic fatty liver disease models: a mechanistic view. Nutrients. 2020;12:499.
Siroma TK, Machate DJ, Zorgetto-Pincheiro VA, Figueiredo PS, Marcelino G, Hiane PA, et al. Polyphenols and omega-3 PUFAs: beneficial outcomes to obesity and its related metabolic diseases. Front Nutr. 2022;8:781622.
Innes JK, Calser PC. Omega-6 fatty acids and inflammation. Prostaglandins Leukot Essent Fatty Acids. 2018;132:41-48.
Sambra V, Echeverria F, Valenzuela A, Chouinard-Watkins R, Valenzuela R. Docosahexaenoic and arachidonic acids as neuroprotective nutrients throughout the life cycle. Nutrients. 2021;13:986.
Valenzuela R, Ortiz M, Hernández-Rodas MC, Echeverría F, Videla LA. Targeting n-3 polyunsaturated fatty acids in non-alcoholic fatty liver disease. Curr Med Chem. 2020;27:5250-5272.
Zúñiga-Hernández J, Sambra V, Echeverría F, Videla LA, Valenzuela R. N-3 PUFAs and their specialized pro-resolving lipid mediators on airway inflammatory response: beneficial effects in the prevention and treatment of respiratory diseases. Food Funct. 2022;13:4260-4272.
Videla LA, Hernandez-Rodas MC, Metherel AH, Valenzuela R. Influence of the nutritional status and oxidative stress in the desaturation and elongation of n-3 and n-6 polyunsaturated fatty acids: impact on non-alcoholic fatty liver disease. Prostaglandins Leukot Essent Fatty Acids. 2022;181:102441.
Araya J, Rodrigo R, Pettinelli P, Araya AV, Poniachik J, Videla LA. Decreased liver fatty acid Δ-6 and Δ-5 desaturase activity in obese patients. Obesity. 2010;18:1460-1463.
Metherel AH, Lacombe RJS, Chouinard-Watkins R, Hopperton KE, Bazinet RP. Complete assessment of whole-body n-3 and n-6 PUFA synthesis-secretion kinetics and DHA turnover in a rodent model. J Lipid Res. 2018;59:357-367.
Domenichiello AF, Kitson AP, Chen CT, Trépanier MO, Stavro PM, Bazinet RP. The effect of linoleic acid on the whole-body synthesis rates of polyunsaturated fatty acids from α-linolenic acid and linoleic acid in free-living rats. J Nutr Biochem. 2016;30:167-176.
Domenichiello AF, Kitson AP, Metherel AH, Chen CT, Hopperton KE, Stavro PM, et al. Whole-body docosahexaenoic acid synthesis-secretion rates in rats are constant across a large range of dietary α-linolenic acid intakes. J Nutr. 2017;147:37-44.
Salem N, Wegher B, Mena P, Uauy R. Arachidonic and docosahexaenoic acids are biosynthesized from their 18-carbon precursors in human infants. Proc Natl Acad Sci U S A. 1996;93:49-54.
Emken EA, Adlof RO, Gulley RM. Dietary linoleic acid influences desaturation and acylation of deuterium-labeled linoleic and linolenic acids in young adult males. Biochim Biophys Acta. 1994;1213:277-288.
Hussein N, Ah-Sing E, Wilkinson P, Leach C, Griffin BA, Millward DJ. Long-chain conversion of [13C] linoleic acid and alpha-linolenic acid in response to marked changes in their dietary intake in men. J Lipid Res. 2005;46:269-280.
McCloy U, Ryan MA, Pencharz PB, Ross RJ, Cunnane SC. A comparison of the metabolism of eighteen-carbon 13C-unsaturated fatty acids in healthy women. J Lipid Res. 2004;45:474-485.
Burns-Whitmore B, Froyen E, Heskey C, Parker T, San PG. Alpha-linolenic and linoleic fatty acids in the vegan diet: do they require dietary reference intake/adequate intake special considerations? Nutrients. 2019;11:2365.
Metherel AH, Scott Lacombe RJ, Chouinard-Watkins R, Bazinet RP. Docosahexaenoic acid is both a product of and a precursor to tetracosahexaenoic acid in the rat. J Lipid Res. 2019;60:412-420.
Bligh EG, Dyer WJ. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959;37:911-917.
Morrison WR, Smith LM. Preparation of fatty acid methyl esters and dimethyl acetals from lipids with boron trifluoride methanol. J Lipid Res. 1964;5:600-608.
Voss A, Reinhart M, Sankarappa S, Sprecher H. The metabolism of 7,10,13,16,19-docosapentaenoic acid to 4,7,10,13,16,19-docosahexaenoic acid in rat livers is independent of a 4-desaturase. J Biol Chem. 1991;266:19995-20000.
Chilton FH, Dutta R, Reynolds L, Sergeant S, Mathias RA, Seeds MC. Precision nutrition and omega-3 polyunsaturated fatty acids: a case for personalized supplementation approaches for the prevention and management of human diseases. Nutrients. 2017;9:1165.
Bazinet RP, Layé S. Polyunsaturated fatty acids and their metabolites in brain function and disease. Nat Rev Neurosci. 2014;15:771-785.
Mason RP, Libby P, Bhatt DL. Emerging mechanisms of cardiovascular protection for the omega-3 fatty acid eicosapentaenoic acid. Arterioscler Thromb Vasc Biol. 2020;40:1135-1147.
Mercuri O, Peluffo RO, Brenner RR. Effect of insulin on the oxidative desaturation of α-linolenic, oleic and palmitic acids. Lipids. 1967;2:284-285.
Ayala S, Brenner RR. Effect of alloxan diabetes on the biosynthesis of unsaturated fatty acids from linoleic and arachidonic acids in rat liver and testis. Acta Physiol Lat Am. 1975;25:371-378.
Nervi AM, Catala A, Brenner RR, Peluffo RO. Dietary and hormonal effects upon activity of "soluble" protein and particulate fraction of fatty acid desaturation system of rat liver microsomes. Lipids. 1975;10:348-352.
Mandon EC, de Gomez Dumm IN, Brenner RR. Effect of epinephrine on the oxidative desaturation of fatty acids in the rat adrenal gland. Lipids. 1986;21:401-404.
Irazú CE, González-Rodríguez S, Brenner RR. Delta 5 desaturase activity in rat kidney microsomes. Mol Cell Biochem. 1993;129:31-37.
Rapoport SI, Igarashi M, Gao F. Quantitative contribution of diet and liver synthesis to docosahexaenoic acid homeostasis. Prostaglandins Leukot Essent Fatty Acids. 2010;82:273-276.
Rincón-Cervera MA, Valenzuela R, Hernandez-Rodas MC, Marambio M, Espinosa A, Mayer S, et al. Supplementation with antioxidant-rich extra virgin olive oil prevents hepatic oxidative stress and reduction of desaturation capacity in mice fed a high-fat diet: effects on fatty acid composition in liver and extrahepatic tissues. Nutrition. 2016;32:1254-1267.
Gregory MK, Gibson RA, Cook-Johnson RJ, Cleland LG, James MJ. Elongase reactions as control points in long-chain polyunsaturated fatty acid synthesis. PLoS One. 2011;6:e29662.
Melton EM, Cerny RL, Watkins PA, DiRusso CC, Black PN. Human fatty acid transport protein 2a/very long chain acyl-CoA synthetase 1 (FATP2a/Acsvl1) has a preference in mediating the channeling of exogenous n-3 fatty acids into phosphatidylinositol. J Biol Chem. 2011;286:30670-30679.
Metherel AH, Richard P, Bazinet RP. Updates to the n-3 polyunsaturated fatty acid biosynthesis pathway: DHA synthesis rates, tetracosahexaenoic acid and (minimal) retroconversion. Prog Lipid Res. 2019;76:101008.
Barrera C, Valenzuela R, Rincón MA, Espinosa A, López-Arana S, González-Mañan D, et al. Iron-induced derangement in hepatic Δ-5 and Δ-6 desaturation capacity and fatty acid profile leading to steatosis: impact on extrahepatic tissues and prevention by antioxidant-rich extra virgin olive oil. Prostaglandins Leukot Essent Fatty Acids. 2020;153:102058.
Nakamura MT, Nara TY. Gene regulation of mammalian desaturases. Biochem Soc Trans. 2002;30:1076-1079.
Li YL, Tian H, Jiang J, Zhang Y, Qi XW. Multifaceted regulation and functions of fatty acid desaturase 2 in human cancers. Am J Cancer Res. 2020;10:4098-4111.
Martinelli N, Consoli L, Olivieri OA. A “desaturase hypothesis” for atherosclerosis: Janus-faced enzymes in omega-6 and omega-3 polyunsaturated fatty acid metabolism. J Nutrigenet Nutrigenomics. 2009;2:129-139.
Chiang N, Serhan CN. Specialized pro-resolving mediator network: an update on production and actions. Essays Biochem. 2020;64:443-462.
Rincón-Cervera MA, Valenzuela R, Hernandez-Rodas MC, Barrera C, Espinosa A, Marambio M, et al. Vegetable oils rich in alpha linolenic acid increment hepatic n-3 LCPUFA, modulating the fatty acid metabolism and antioxidant response in rats. Prostaglandins Leukot Essent Fatty Acids. 2016;111:25-35.
Simopoulos AP. The importance of the ratio of omega-6/omega-3 essential fatty acids. Biomed Pharmacother. 2002;56:365-379.
Peng Y, Zhou T, Wang Q, Liu P, Zhang T, Zetterström R, et al. Fatty acid composition of diet, cord blood and breast milk in Chinese mothers with different dietary habits. Prostaglandins Leukot Essent Fatty Acids. 2009;81:325-330.
Lassek WD, Gaulin SJC. Linoleic and docosahexaenoic acids in human milk have opposite relationships with cognitive test performance in a sample of 28 countries. Prostaglandins Leukot Essent Fatty Acids. 2014;91:195-201.
Choque B, Catheline D, Rioux V, Legrand P. Linoleic acid: between doubts and certainties. Biochimie. 2014;96:14-21.
Naughton SS, Mathai ML, Hryciw DH, McAinch AJ. Linoleic acid and the pathogenesis of obesity. Prostaglandins Other Lipid Mediat. 2016;125:90-99.
Oosting A, Kegler D, van de Heijning BJ, Verkade HJ, van der Beek EM. Reduced linoleic acid intake in early postnatal life improves metabolic outcomes in adult rodents following a Western-style diet challenge. Nutr Res. 2015;35:800-811.
Nindrea RD, Aryandono T, Lazuardi L, Dwiprahasto I. Association of dietary intake ratio of n-3/n-6 polyunsaturated fatty acids with breast cancer risk in Western and Asian countries: a meta-analysis. Asian Pac J Cancer Prev. 2019;20:1321-1327.
Valenzuela R, Videla LA. The importance of the long-chain polyunsaturated fatty acid n-6/n-3 ratio in development of non-alcoholic fatty liver associated with obesity. Food Funct. 2011;2:644-648.
Suter MA, Ma J, Vuguin PM, Hartil K, Fiallo A, Harris RA, et al. In utero exposure to a maternal high-fat diet alters the epigenetic histone code in a murine model. Am J Obstet Gynecol. 2014;210(463):e1-463.e11.
Valenzuela R, Echeverria F, Ortiz M, Rincón-Cervera MÁ, Espinosa A, Hernández-Rodas MC, et al. Hydroxytyrosol prevents reduction in liver activity of Δ-5 and Δ-6 desaturases, oxidative stress, and depletion in long chain polyunsaturated fatty acid content in different tissues of high-fat diet fed mice. Lipids Health Dis. 2017;16:64.