Evidence map›Paper›PMID 25287287›Full record

ReviewNature reviews. Endocrinology2014

Branched-chain amino acids in metabolic signalling and insulin resistance.

Christopher J Lynch, Sean H Adams

4 registry-linked trialsOpen access · greenAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Nature reviews. Endocrinology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 4 registered trials, which are not on this map. Cited by 842 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
842citing papers in PubMed, 7 pooled it
33.2field-weighted citation impact, top 1% 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.

NCT02684565 nacompletednot on this mapstarted 2016, after this paper: background citation

Effects of Branch Chain Amino Acids on Glucose Tolerance in Obese Pre-Diabetic Subjects

TypeinterventionalSponsorUniversity of California, Los AngelesRan2016 to 2018Enrolled11ConditionsPrediabetic StateArmsBCAA High Protein supplement, BCAA Low Protein supplement
NCT03627104 nacompletednot on this mapstarted 2018, after this paper: background citation

Effect of Dietary Protein and Energy Restriction in the Improvement of Insulin Resistance in Subjects With Obesity

TypeinterventionalSponsorInstituto Nacional de Ciencias Medicas y Nutricion Salvador ZubiranRan2018 to 2020Enrolled80ConditionsObesity, Insulin ResistanceArmsNormoprotein diet with animal protein, Normoprotein diet with vegetable protein, High-protein diet with animal protein, High-protein diet with vegetable protein
NCT04886973 nacompletednot on this mapstarted 2022, after this paper: background citation

Effect of Insulin Resistance on Branched Chain Amino Acid Metabolism.

TypeinterventionalSponsorInstituto Nacional de Ciencias Medicas y Nutricion Salvador ZubiranRan2022 to 2022Enrolled40ConditionsObesity, Insulin ResistanceArmsAdministration of an 8% crystalline L-amino acid solution with high concentrations of branched chain amino acids.
NCT06107933 recruitingnot on this mapstarted 2023, after this paper: background citation

Developmental Impacts of MicroPLastics Exposure in Early Life

TypeobservationalSponsorJohns Hopkins Bloomberg School of Public HealthRan2023 to 2027Enrolled40ConditionsInfant Development, Breast Feeding, Environmental ExposureArmsObservational only
3 · Its place in the literature

Who cites it

842 citing papers in PubMed, 7 syntheses or guidelines pooled it, 1,381 citations in OpenAlex.

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  16. GutiMeta · 2026
    Article
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  20. The emerging role of branched-chain amino acid metabolism in obesity.International journal of obesity (2005) · 2026
    Review

782 more citing papers are in PubMed but not listed here.

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

2 authors at 2 institutions in 1 country.

Christopher J LynchCellular and Molecular Physiology Department, The Pennsylvania State University, 500 University Drive, MC-H166, Hershey, PA 17033, USA.
Sean H AdamsArkansas Children's Nutrition Center, and Department of Pediatrics, University of Arkansas for Medical Sciences, 15 Children's Way, Little Rock, AR 72202, USA.
Arkansas Children's Nutrition Center · USPennsylvania State University · US

Funding

Identification of Muscle-Specific Biomarkers of Fatty Acid beta-OxidationR01DK078328 · NIDDK · U.S. AGRICULTURAL RESEARCH SERVICE · PI ADAMS, SEAN HARRISON · 2008 to 2012
$1.8M
Mechanisms of drug side effects related to obesity and diabetesR01DK084428 · NIDDK · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · PI LYNCH, CHRISTOPHER JOHN · 2010 to 2013
$1.3M
Adipose Organ Transplant for Treatment of Maple Syrup Urine DiseaseR21DK091784 · NIDDK · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · PI LYNCH, CHRISTOPHER JOHN · 2011 to 2012
$421k
NIDDK NIH HHS R01 DK078328NIDDK NIH HHS R01 DK084428NIDDK NIH HHS R21 DK091784
6 · The paper itself

Abstract

Branched-chain amino acids (BCAAs) are important nutrient signals that have direct and indirect effects. Frequently, BCAAs have been reported to mediate antiobesity effects, especially in rodent models. However, circulating levels of BCAAs tend to be increased in individuals with obesity and are associated with worse metabolic health and future insulin resistance or type 2 diabetes mellitus (T2DM). A hypothesized mechanism linking increased levels of BCAAs and T2DM involves leucine-mediated activation of the mammalian target of rapamycin complex 1 (mTORC1), which results in uncoupling of insulin signalling at an early stage. A BCAA dysmetabolism model proposes that the accumulation of mitotoxic metabolites (and not BCAAs per se) promotes β-cell mitochondrial dysfunction, stress signalling and apoptosis associated with T2DM. Alternatively, insulin resistance might promote aminoacidaemia by increasing the protein degradation that insulin normally suppresses, and/or by eliciting an impairment of efficient BCAA oxidative metabolism in some tissues. Whether and how impaired BCAA metabolism might occur in obesity is discussed in this Review. Research on the role of individual and model-dependent differences in BCAA metabolism is needed, as several genes (BCKDHA, PPM1K, IVD and KLF15) have been designated as candidate genes for obesity and/or T2DM in humans, and distinct phenotypes of tissue-specific branched chain ketoacid dehydrogenase complex activity have been detected in animal models of obesity and T2DM.

Indexed as

Insulin ResistanceAmino Acids, Branched-ChainAnimalsBlood GlucoseDiabetes Mellitus, Type 2HumansInsulinMechanistic Target of Rapamycin Complex 1Multiprotein ComplexesObesitySignal TransductionTOR Serine-Threonine KinasesAmino Acids, Branched-ChainBlood GlucoseInsulinMechanistic Target of Rapamycin Complex 1Multiprotein ComplexesTOR Serine-Threonine Kinases

Identifiers

PMID25287287
PMCPMC4424797
OpenAlexW2002364623

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

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.