Evidence map›Paper›PMID 25400942›Full record

ArticleJournal of nutrition and metabolism2014

Leucine Modulates Mitochondrial Biogenesis and SIRT1-AMPK Signaling in C2C12 Myotubes.

Chunzi Liang, Benjamin J Curry, Patricia L Brown, Michael B Zemel

Registry-linked trialOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of nutrition and metabolism, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04751916 (Nutritional Stimulation of Muscle Protein Synthesis and Metabolic Rate After Bariatric Surgery), which is not on this map. Cited by 54 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed, 1 pooled it
5.0field-weighted citation impact, top 5% 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.

NCT04751916 naunknown statusnot on this mapstarted 2021, after this paper: background citation

Nutritional Stimulation of Muscle Protein Synthesis and Metabolic Rate After Bariatric Surgery

TypeinterventionalSponsorOregon Health and Science UniversityRan2021 to 2024Enrolled40ConditionsWeight LossArmsEssential Amino Acid Protein Supplement, Beneprotein®
3 · Its place in the literature

Who cites it

54 citing papers in PubMed, 1 synthesis or guideline pooled it, 119 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
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  7. Article
  8. Article
  9. Citric Acid Cycle Genes and Nutrigenetics.International journal of molecular sciences · 2026
    Review
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  12. Article
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  14. Article
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  16. Article
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  19. Review
  20. Uridine alleviates high-carbohydrate diet-induced metabolic syndromes by activatingAnimal nutrition (Zhongguo xu mu shou yi xue hui) · 2023
    Article
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

4 authors at 2 institutions in 1 country.

Chunzi LiangDepartment of Nutrition, University of Tennessee, Knoxville, 1215 W. Cumberland Avenue, 229 Jessie Harris Building, Knoxville, TN 37996-1920, USA.
Benjamin J CurryEnsion, Inc., 11020 Solway School Road, Suite 108, Knoxville, TN 37931, USA.
Patricia L BrownDepartment of Nutrition, University of Tennessee, Knoxville, 1215 W. Cumberland Avenue, 229 Jessie Harris Building, Knoxville, TN 37996-1920, USA.
Michael B ZemelNuSirt Biopharma, 11020 Solway School Road, Suite 109, Knoxville, TN 37931, USA.
University of Tennessee at Knoxville · USEnsion · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Previous studies from this laboratory demonstrate that dietary leucine protects against high fat diet-induced mitochondrial impairments and stimulates mitochondrial biogenesis and energy partitioning from adipocytes to muscle cells through SIRT1-mediated mechanisms. Moreover, β-hydroxy-β-methyl butyrate (HMB), a metabolite of leucine, has been reported to activate AMPK synergistically with resveratrol in C2C12 myotubes. Therefore, we hypothesize that leucine-induced activation of SIRT1 and AMPK is the central event that links the upregulated mitochondrial biogenesis and fatty acid oxidation in skeletal muscle. Thus, C2C12 myotubes were treated with leucine (0.5 mM), alanine (0.5 mM), valine (0.5 mM), EX527 (SIRT1 inhibitor, 25 μM), and Compound C (AMPK inhibitor, 25 μM) alone or in combination to determine the roles of AMPK and SIRT1 in leucine-modulation of energy metabolism. Leucine significantly increased mitochondrial content, mitochondrial biogenesis-related genes expression, fatty acid oxidation, SIRT1 activity and gene expression, and AMPK phosphorylation in C2C12 myotubes compared to the controls, while EX527 and Compound C markedly attenuated these effects. Furthermore, leucine treatment for 24 hours resulted in time-dependent increases in cellular NAD(+), SIRT1 activity, and p-AMPK level, with SIRT1 activation preceding that of AMPK, indicating that leucine activation of SIRT1, rather than AMPK, is the primary event.

Identifiers

PMID25400942
PMCPMC4220583
OpenAlexW2125543086

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.