Evidence map›Paper›PMID 26182429›Full record

ArticleBioscience reports2015

High homocysteine induces betaine depletion.

Apolline Imbard, Jean-François Benoist, Ruben Esse, Sapna Gupta, Sophie Lebon, An S de Vriese, Helene Ogier de Baulny, Warren Kruger, Manuel Schiff, Henk J Blom

Open access · goldAbstract read
In one paragraph

Article in Bioscience reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
3.0field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 7 institutions in 4 countries.

Apolline ImbardBiochemistry Hormonology Laboratory, Robert-Debré Hospital, APHP, 48 Bd Serurier, Paris 75019, France Paris Sud University, Pharmacy Faculty, 5 rue Jean Baptiste Clément, Chatenay-Malabry 92019, France apolline.imbard@rdb.aphp.fr.
Jean-François BenoistBiochemistry Hormonology Laboratory, Robert-Debré Hospital, APHP, 48 Bd Serurier, Paris 75019, France Paris Sud University, Pharmacy Faculty, 5 rue Jean Baptiste Clément, Chatenay-Malabry 92019, France.
Ruben EsseInstitute for Medicines and Pharmaceutical Sciences (iMed.UL), Faculty of Pharmacy, University of Lisbon, Lisbon 1649-003, Portugal.
Sapna GuptaCancer Biology Program, Fox Chase Cancer Center, Philadelphia, PA 19111, U.S.A.
Sophie LebonINSERM UMR 1141, Hôpital Robert Debré, 48 Bd Serurier, Paris 75019, France.
An S de VrieseRenal Unit, Department of Internal Medicine, AZ Sint-Jan AV, Bruges 8000, Belgium.
Helene Ogier de Baulny*Reference Center for Inherited Metabolic Diseases, Robert-Debré Hospital, APHP, Paris 75019, France.
Warren KrugerCancer Biology Program, Fox Chase Cancer Center, Philadelphia, PA 19111, U.S.A.
Manuel SchiffINSERM UMR 1141, Hôpital Robert Debré, 48 Bd Serurier, Paris 75019, France *Reference Center for Inherited Metabolic Diseases, Robert-Debré Hospital, APHP, Paris 75019, France †Faculté de Médecine Denis Diderot, Université Paris Diderot-Paris 7, Paris 75013, France.
Henk J Blom‡Laboratory for Clinical Biochemistry and Metabolism, Department of General Pediatrics, Center for Pediatrics and Adolescent Medicine University Hospital, Freiburg D-79106, Germany.
NeuroDiderotAssistance Publique – Hôpitaux de Paris · FRAZ Sint-Jan · BEHôpital Robert-Debré · FRUniversité Paris-Sud · FRUniversity Medical Center Freiburg · DEUniversity of Lisbon · PT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Betaine is the substrate of the liver- and kidney-specific betaine-homocysteine (Hcy) methyltransferase (BHMT), an alternate pathway for Hcy remethylation. We hypothesized that BHMT is a major pathway for homocysteine removal in cases of hyperhomocysteinaemia (HHcy). 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 β-synthase (CBS) deficiency. S-adenosyl-methionine (AdoMet), S-adenosyl-homocysteine (AdoHcy), methionine, betaine and dimethylglycine (DMG) were quantified by ESI-LC-MS/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.

Indexed as

AnimalsBetaineBetaine-Homocysteine S-MethyltransferaseCarrier ProteinsDisease Models, AnimalFemaleGABA Plasma Membrane Transport ProteinsHomocysteineHomocystinuriaHumansMaleMiceMice, TransgenicRatsRats, WistarBetaineBetaine-Homocysteine S-Methyltransferasebetaine plasma membrane transport proteinsBHMT protein, humanBhmt protein, mouseBhmt protein, ratCarrier ProteinsGABA Plasma Membrane Transport ProteinsHomocysteineSlc6a12 protein, mousebetainecystathionine-β-synthase deficiencyhyperhomocysteinaemiaS-adenosyl-methionine

Identifiers

PMID26182429
PMCPMC4613678
OpenAlexW2325820198

What OpenQuestion holds

Textmetadata
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.