Evidence map›Paper›PMID 26858359›Full record

ArticleDiabetes2016

Dietary Betaine Supplementation Increases Fgf21 Levels to Improve Glucose Homeostasis and Reduce Hepatic Lipid Accumulation in Mice.

Asma Ejaz, Laura Martinez-Guino, Allison B Goldfine, Francesc Ribas-Aulinas, Valeria De Nigris, Sílvia Ribó, Alba Gonzalez-Franquesa, Pablo M Garcia-Roves, Elizabeth Li, Jonathan M Dreyfuss and 7 more

Open access · bronzeAbstract read
In one paragraph

Article in Diabetes, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed, 1 pooled it
5.6field-weighted citation impact, top 4% 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

57 citing papers in PubMed, 1 synthesis or guideline pooled it, 105 citations in OpenAlex.

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  6. Effect of Dapagliflozin on Urine Metabolome in Patients with Type 2 Diabetes.The Journal of clinical endocrinology and metabolism · 2021
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  10. Early-Life Betaine Supplementation Drives Sex-Specific Metabolic Programming in Rats, Affecting FGF21 Signaling and Energy Balance.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
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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

17 authors at 9 institutions in 2 countries.

Asma EjazResearch Division, Joslin Diabetes Center, and Harvard Medical School, Boston, MA.
Laura Martinez-GuinoEndocrinology Section, Hospital Sant Joan de Déu, Barcelona, Spain.
Allison B GoldfineResearch Division, Joslin Diabetes Center, and Harvard Medical School, Boston, MA.
Francesc Ribas-AulinasDepartment of Biochemistry and Molecular Biology, Institute of Biomedicine, University of Barcelona, and CIBER Fisiopatología de la Obesidad y Nutrición, Barcelona, Spain.
Valeria De NigrisDiabetes and Obesity Laboratory, Institut d'Investigacions Biomèdiques August Pi Sunyer, Barcelona, Spain.
Sílvia RibóEndocrinology Section, Hospital Sant Joan de Déu, Barcelona, Spain.
Alba Gonzalez-FranquesaDiabetes and Obesity Laboratory, Institut d'Investigacions Biomèdiques August Pi Sunyer, Barcelona, Spain.
Pablo M Garcia-RovesDiabetes and Obesity Laboratory, Institut d'Investigacions Biomèdiques August Pi Sunyer, Barcelona, Spain CIBERDEM, Barcelona, Spain Department of Physiological Sciences II, University of Barcelona, Barcelona, Spain.
Elizabeth LiResearch Division, Joslin Diabetes Center, and Harvard Medical School, Boston, MA.
Jonathan M DreyfussResearch Division, Joslin Diabetes Center, and Harvard Medical School, Boston, MA Department of Biomedical Engineering, Boston University, Boston, MA.
Walt GallMetabolon, Inc., Durham, NC.
Jason K KimProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA.
Teodoro BottiglieriInstitute of Metabolic Disease, Baylor Research Institute, Dallas, TX.
Francesc VillarroyaDepartment of Biochemistry and Molecular Biology, Institute of Biomedicine, University of Barcelona, and CIBER Fisiopatología de la Obesidad y Nutrición, Barcelona, Spain.
Robert E GersztenMassachusetts General Hospital and Harvard Medical School, Boston, MA.
Mary-Elizabeth PattiResearch Division, Joslin Diabetes Center, and Harvard Medical School, Boston, MA clerin@fsjd.org mary.elizabeth.patti@joslin.harvard.edu.
Carles LerinEndocrinology Section, Hospital Sant Joan de Déu, Barcelona, Spain clerin@fsjd.org mary.elizabeth.patti@joslin.harvard.edu.
Harvard University · USHospital Sant Joan de Déu Barcelona · ESConsorci Institut D'Investigacions Biomediques August Pi I Sunyer · ESJoslin Diabetes Center · USUniversitat de Barcelona · ESCentro de Investigación Biomédica en Red · ESMassachusetts General Hospital · USMetabolon (United States) · USUniversity of Massachusetts Chan Medical School · US

Funding

SPECIAL ASSAY COREP30DK036836 · NIDDK · JOSLIN DIABETES CENTER · PI JEAN E. SCHAFFER · 1986 to 2026
$50.5M
Metabolomic predictors of insulin resistance and diabetesR01DK081572 · NIDDK · VANDERBILT UNIVERSITY · PI CLISH, CLARY B, GERSZTEN, ROBERT E · 2008 to 2025
$9.3M
UMass Mouse Metabolic Phenotyping Center - Metabolism CoreU2CDK093000 · NIDDK · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI KIM, JASON K · 2016 to 2021
$4.6M
UMass Mouse Metabolic Phenotyping CenterU24DK093000 · NIDDK · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI KIM, JASON K · 2011 to 2015
$2.1M
NIDDK NIH HHS P30 DK036836NIDDK NIH HHS R01 DK081572NIDDK NIH HHS U24 DK093000NIDDK NIH HHS U2C DK093000
6 · The paper itself

Abstract

Identifying markers of human insulin resistance may permit development of new approaches for treatment and prevention of type 2 diabetes. To this end, we analyzed the fasting plasma metabolome in metabolically characterized human volunteers across a spectrum of insulin resistance. We demonstrate that plasma betaine levels are reduced in insulin-resistant humans and correlate closely with insulin sensitivity. Moreover, betaine administration to mice with diet-induced obesity prevents the development of impaired glucose homeostasis, reduces hepatic lipid accumulation, increases white adipose oxidative capacity, and enhances whole-body energy expenditure. In parallel with these beneficial metabolic effects, betaine supplementation robustly increased hepatic and circulating fibroblast growth factor (Fgf)21 levels. Betaine administration failed to improve glucose homeostasis and liver fat content in Fgf21(-/-) mice, demonstrating that Fgf21 is necessary for betaine's beneficial effects. Together, these data indicate that dietary betaine increases Fgf21 levels to improve metabolic health in mice and suggest that betaine supplementation merits further investigation as a supplement for treatment or prevention of type 2 diabetes in humans.

Indexed as

AdultAnimalsBetaineCells, CulturedDietary SupplementsFatty LiverFemaleFibroblast Growth FactorsGlucoseGlucose IntoleranceHomeostasisHumansLipid MetabolismLiverMaleMiceBetainefibroblast growth factor 21Fibroblast Growth FactorsGlucose

Identifiers

PMID26858359
PMCPMC4806659
OpenAlexW2307485186

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.