Evidence map›Paper›PMID 33480176›Full record

ArticleJournal of diabetes investigation2021

Kruppel-like factor 15 regulates fuel switching between glucose and fatty acids in brown adipocytes.

Yuko Nabatame, Tetsuya Hosooka, Chikako Aoki, Yusei Hosokawa, Makoto Imamori, Yoshikazu Tamori, Yuko Okamatsu-Ogura, Takeshi Yoneshiro, Shingo Kajimura, Masayuki Saito and 1 more

Open access · goldAbstract read
In one paragraph

Article in Journal of diabetes investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.3field-weighted citation impact, top 21% 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

12 citing papers in PubMed, 17 citations in OpenAlex.

  1. Trial
  2. Article
  3. Article
  4. Article
  5. Article
  6. Frontiers in nutrition · 2025
    Article
  7. NFκB and JNK pathways mediate metabolic adaptation upon ESCRT-I deficiency.Cellular and molecular life sciences : CMLS · 2024
    Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. 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

11 authors at 3 institutions in 2 countries.

Yuko NabatameDivision of Diabetes and Endocrinology, Kobe University Graduate School of Medicine, Kobe, Japan.
Tetsuya HosookaDivision of Diabetes and Endocrinology, Kobe University Graduate School of Medicine, Kobe, Japan.ORCID https://orcid.org/0000-0002-9944-5418
Chikako AokiDivision of Diabetes and Endocrinology, Kobe University Graduate School of Medicine, Kobe, Japan.
Yusei HosokawaDivision of Diabetes and Endocrinology, Kobe University Graduate School of Medicine, Kobe, Japan.ORCID https://orcid.org/0000-0003-1684-8121
Makoto ImamoriDivision of Diabetes and Endocrinology, Kobe University Graduate School of Medicine, Kobe, Japan.
Yoshikazu TamoriDivision of Diabetes and Endocrinology, Kobe University Graduate School of Medicine, Kobe, Japan.ORCID https://orcid.org/0000-0003-3653-5683
Yuko Okamatsu-OguraLaboratory of Biochemistry, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Takeshi YoneshiroUCSF Diabetes Center, University of California, San Francisco, California, USA.
Shingo KajimuraUCSF Diabetes Center, University of California, San Francisco, California, USA.
Masayuki SaitoLaboratory of Biochemistry, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Wataru OgawaDivision of Diabetes and Endocrinology, Kobe University Graduate School of Medicine, Kobe, Japan.ORCID https://orcid.org/0000-0002-0432-4366
Kobe University · JPHokkaido University · JPUniversity of California, San Francisco · US

Funding

Mitochondrial Metabolite Compartmentalization in Health and DiseaseDP1DK126160 · NIDDK · BETH ISRAEL DEACONESS MEDICAL CENTER · PI KAJIMURA, SHINGO · 2020 to 2025
$4.4M
Molecular control of beige fat heterogeneityR01DK125281 · NIDDK · BETH ISRAEL DEACONESS MEDICAL CENTER · PI KAJIMURA, SHINGO · 2020 to 2023
$1.9M
Mitochondrial BCAA transporter in physiology and diseaseR01DK125283 · NIDDK · BETH ISRAEL DEACONESS MEDICAL CENTER · PI KAJIMURA, SHINGO · 2021 to 2025
$1.8M
NIDDK NIH HHS DP1 DK126160NIDDK NIH HHS R01 DK125281NIDDK NIH HHS R01 DK125283
6 · The paper itself

Abstract

AIMS/

introductionBrown adipose tissue (BAT) utilizes large amounts of fuel for thermogenesis, but the mechanism by which fuel substrates are switched in response to changes in energy status is poorly understood. We have now investigated the role of Kruppel-like factor 15 (KLF15), a transcription factor expressed at a high level in adipose tissue, in the regulation of fuel utilization in BAT. MATERIALS AND

methodsDepletion or overexpression of KLF15 in HB2 differentiated brown adipocytes was achieved by adenoviral infection. Glucose and fatty acid oxidation were measured with radioactive substrates, pyruvate dehydrogenase complex activity was determined with a colorimetric assay, and gene expression was examined by reverse transcription and real-time polymerase chain reaction analysis.

resultsKnockdown of KLF15 in HB2 cells attenuated fatty acid oxidation in association with downregulation of the expression of genes related to this process including Acox1 and Fatp1, whereas it increased glucose oxidation. Expression of the gene for pyruvate dehydrogenase kinase 4 (PDK4), a negative regulator of pyruvate dehydrogenase complex, was increased or decreased by KLF15 overexpression or knockdown, respectively, in HB2 cells, with these changes being accompanied by a respective decrease or increase in pyruvate dehydrogenase complex activity. Chromatin immunoprecipitation showed that Pdk4 is a direct target of KLF15 in HB2 cells. Finally, fasting increased expression of KLf15, Pdk4 and genes involved in fatty acid utilization in BAT of mice, whereas refeeding suppressed Klf15 and Pdk4 expression.

conclusionsOur results implicate KLF15 in the regulation of fuel switching between glucose and fatty acids in response to changes in energy status in BAT.

Indexed as

Acyl-CoA OxidaseAdipocytes, BrownAdipose Tissue, BrownAnimalsCell DifferentiationDown-RegulationEnergy MetabolismFastingFatty AcidsFatty Acid Transport ProteinsGene Expression RegulationGlucoseKruppel-Like Transcription FactorsMiceOxidation-ReductionPyruvate Dehydrogenase Acetyl-Transferring KinaseACOX1 protein, mouseAcyl-CoA OxidaseFatty AcidsFatty Acid Transport ProteinsGlucoseKlf15 protein, mouseKruppel-Like Transcription FactorsPdk4 protein, mousePyruvate Dehydrogenase Acetyl-Transferring KinasePyruvate Dehydrogenase ComplexSlc27a1 protein, mouseBrown adipose tissueFuel switchingKruppel-like factor 15

Identifiers

PMID33480176
PMCPMC8264414
OpenAlexW3123712892

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.