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Therefore, we measured betaine in plasma and tissues from patients and animal models of HHcy of genetic and acquired cause. Plasma was collected from patients presenting HHcy without any Hcy interfering treatment. Plasma and tissues were collected from rat models of HHcy induced by diet and from a mouse model of cystathionine \u03b2-synthase (CBS) deficiency. S-adenosyl-methionine (AdoMet), S-adenosyl-homocysteine (AdoHcy), methionine, betaine and dimethylglycine (DMG) were quantified by ESI\u2014LC\u2013MS\/MS. mRNA expression was quantified using quantitative real-time (QRT)-PCR. For all patients with diverse causes of HHcy, plasma betaine concentrations were below the normal values of our laboratory. In the diet-induced HHcy rat model, betaine was decreased in all tissues analysed (liver, brain, heart). In the mouse CBS deficiency model, betaine was decreased in plasma, liver, heart and brain, but was conserved in kidney. Surprisingly, BHMT expression and activity was decreased in liver. However, in kidney, BHMT and SLC6A12 expression was increased in CBS-deficient mice. Chronic HHcy, irrespective of its cause, induces betaine depletion in plasma and tissues (liver, brain and heart), indicating a global decrease in the body betaine pool. In kidney, betaine concentrations were not affected, possibly due to overexpression of the betaine transporter SLC6A12 where betaine may be conserved because of its crucial role as an osmolyte.<\/jats:p>","DOI":"10.1042\/bsr20150094","type":"journal-article","created":{"date-parts":[[2015,4,30]],"date-time":"2015-04-30T09:01:47Z","timestamp":1430384507000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["High homocysteine induces betaine depletion"],"prefix":"10.1042","volume":"35","author":[{"given":"Apolline","family":"Imbard","sequence":"first","affiliation":[{"name":"Biochemistry Hormonology Laboratory, Robert-Debr\u00e9 Hospital, APHP, 48 Bd Serurier, Paris 75019, France"},{"name":"Paris Sud University, Pharmacy Faculty, 5 rue Jean Baptiste Cl\u00e9ment, Chatenay-Malabry 92019, France"}]},{"given":"Jean-Fran\u00e7ois","family":"Benoist","sequence":"additional","affiliation":[{"name":"Biochemistry Hormonology Laboratory, Robert-Debr\u00e9 Hospital, APHP, 48 Bd Serurier, Paris 75019, France"},{"name":"Paris Sud University, Pharmacy Faculty, 5 rue Jean Baptiste Cl\u00e9ment, Chatenay-Malabry 92019, France"}]},{"given":"Ruben","family":"Esse","sequence":"additional","affiliation":[{"name":"Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Faculty of Pharmacy, University of Lisbon, Lisbon 1649-003, Portugal"}]},{"given":"Sapna","family":"Gupta","sequence":"additional","affiliation":[{"name":"Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, PA 19111, U.S.A."}]},{"given":"Sophie","family":"Lebon","sequence":"additional","affiliation":[{"name":"INSERM UMR 1141, H\u00f4pital Robert Debr\u00e9, 48 Bd Serurier, Paris 75019, France"}]},{"given":"An\u00a0S","family":"de Vriese","sequence":"additional","affiliation":[{"name":"Renal Unit, Department of Internal Medicine, AZ Sint-Jan AV, Bruges 8000, Belgium"}]},{"given":"Helene\u00a0Ogier","family":"de Baulny","sequence":"additional","affiliation":[{"name":"*Reference Center for Inherited Metabolic Diseases, Robert-Debr\u00e9 Hospital, APHP, Paris 75019, France"}]},{"given":"Warren","family":"Kruger","sequence":"additional","affiliation":[{"name":"Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, PA 19111, U.S.A."}]},{"given":"Manuel","family":"Schiff","sequence":"additional","affiliation":[{"name":"INSERM UMR 1141, H\u00f4pital Robert Debr\u00e9, 48 Bd Serurier, Paris 75019, France"},{"name":"*Reference Center for Inherited Metabolic Diseases, Robert-Debr\u00e9 Hospital, APHP, Paris 75019, France"},{"name":"\u2020Facult\u00e9 de M\u00e9decine Denis Diderot, Universit\u00e9 Paris Diderot\u2013Paris 7, Paris 75013, France"}]},{"given":"Henk\u00a0J.","family":"Blom","sequence":"additional","affiliation":[{"name":"\u2021Laboratory for Clinical Biochemistry and Metabolism, Department of General Pediatrics, Center for Pediatrics and Adolescent Medicine University Hospital, Freiburg D-79106, Germany"}]}],"member":"288","published-online":{"date-parts":[[2015,7,7]]},"reference":[{"key":"2021111618180626300_B1","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1007\/s00726-006-0432-9","article-title":"Mechanisms of homocysteine toxicity in humans","volume":"32","author":"Perla-Kajan","year":"2007","journal-title":"Amino Acids."},{"key":"2021111618180626300_B2","doi-asserted-by":"crossref","first-page":"405","DOI":"10.18388\/abp.2004_3580","article-title":"Methylation demand: a key determinant of homocysteine metabolism","volume":"51","author":"Brosnan","year":"2004","journal-title":"Acta Biochim. 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