Evidence map›Paper›PMID 38653240›Full record

ArticleCell2024

BCAA-nitrogen flux in brown fat controls metabolic health independent of thermogenesis.

Anthony R P Verkerke, Dandan Wang, Naofumi Yoshida, Zachary H Taxin, Xu Shi, Shuning Zheng, Yuka Li, Christopher Auger, Satoshi Oikawa, Jin-Seon Yook and 13 more

Open access · hybridAbstract read
In one paragraph

Article in Cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed
26.8field-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.

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

59 citing papers in PubMed, 82 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Mitochondrial control of glycerolipid synthesis by a PEP shuttle.bioRxiv : the preprint server for biology · 2026
    Article
  17. Review
  18. Article
  19. Advances in Adipose Tissue Biology.Endocrine reviews · 2026
    Review
  20. 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

23 authors at 7 institutions in 2 countries.

Anthony R P VerkerkeDivision of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, and Howard Hughes Medical Institute, Boston, MA, USA.
Dandan WangDivision of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, and Howard Hughes Medical Institute, Boston, MA, USA.
Naofumi YoshidaDivision of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, and Howard Hughes Medical Institute, Boston, MA, USA.
Zachary H TaxinDivision of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, and Howard Hughes Medical Institute, Boston, MA, USA.
Xu ShiDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
Shuning ZhengDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
Yuka LiGraduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
Christopher AugerDivision of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, and Howard Hughes Medical Institute, Boston, MA, USA.
Satoshi OikawaDivision of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, and Howard Hughes Medical Institute, Boston, MA, USA.
Jin-Seon YookDivision of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, and Howard Hughes Medical Institute, Boston, MA, USA.
Melia Granath-PaneloDivision of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, and Howard Hughes Medical Institute, Boston, MA, USA.
Wentao HeDuke Molecular Physiology Institute, Duke School of Medicine, Department of Medicine, Division of Endocrinology, Metabolism and Nutrition, Duke University, Durham, NC, USA.
Guo-Fang ZhangDuke Molecular Physiology Institute, Duke School of Medicine, Department of Medicine, Division of Endocrinology, Metabolism and Nutrition, Duke University, Durham, NC, USA.
Mami MatsushitaDepartment of Nutrition, School of Nursing and Nutrition, Tenshi College, Sapporo, Japan.
Masayuki SaitoLaboratory of Biochemistry, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Robert E GersztenDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
Evanna L MillsDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute and Department of Immunology, Harvard Medical School, Boston, MA, USA.
Alexander S BanksDivision of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
Yasushi IshihamaGraduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
Phillip J WhiteDuke Molecular Physiology Institute, Duke School of Medicine, Department of Medicine, Division of Endocrinology, Metabolism and Nutrition, Department of Pharmacology and Cancer Biology, Duke University, Durham, NC, USA.
Robert W McGarrahDuke Molecular Physiology Institute, Duke School of Medicine, Sarah W. Stedman Nutrition and Metabolism Center, Department of Medicine, Division of Cardiology, Duke University, Durham, NC, USA.
Takeshi YoneshiroDivision of Metabolic Medicine, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan; Division of Molecular Physiology and Metabolism, Tohoku University Graduate School of Medicine, Sendai, Japan.
Shingo KajimuraDivision of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, and Howard Hughes Medical Institute, Boston, MA, USA. Electronic address: skajimur@bidmc.harvard.edu.
Beth Israel Deaconess Medical Center · USDuke University · USKyoto University · JPHarvard University · USHokkaido University · JPTenshi College · JPTohoku University · JP

Funding

Metabolomic predictors of insulin resistance and diabetesR01DK081572 · NIDDK · VANDERBILT UNIVERSITY · PI CLISH, CLARY B, GERSZTEN, ROBERT E · 2008 to 2025
$9.3M
INTEGRATED ENDOCRINE &METABOLIC RESEARCH TRAININGT32DK007516 · NIDDK · BETH ISRAEL DEACONESS MEDICAL CENTER · PI BARBARA B. KAHN · 1986 to 2026
$6.8M
Molecular mechanisms of UCP1-independent pathways in metabolic healthR01DK097441 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Shingo Kajimura · 2012 to 2026
$5.9M
Mitochondrial Metabolite Compartmentalization in Health and DiseaseDP1DK126160 · NIDDK · BETH ISRAEL DEACONESS MEDICAL CENTER · PI KAJIMURA, SHINGO · 2020 to 2025
$4.4M
Mechanisms Connecting Dysregulated Branched-Chain Alpha-Ketoacid Metabolism to Cardiac DysfunctionR01HL160689 · NHLBI · DUKE UNIVERSITY · PI Robert Walker McGarrah · 2022 to 2026
$2.6M
Mechanisms linking the Branched-Chain alpha-Keto Acid regulatory network to the pathogenesis of NASHR01DK135474 · NIDDK · DUKE UNIVERSITY · PI Phillip J White · 2023 to 2026
$2.0M
CalRepository: A database of indirect calorimetry experiments for the study of energy homeostasisR01DK133948 · NIDDK · BETH ISRAEL DEACONESS MEDICAL CENTER · PI BANKS, ALEXANDER · 2022 to 2025
$2.0M
Mitochondrial BCAA transporter in physiology and diseaseR01DK125283 · NIDDK · BETH ISRAEL DEACONESS MEDICAL CENTER · PI KAJIMURA, SHINGO · 2021 to 2025
$1.8M
Instrumentation for Noninvasive Measurement of Glucose and Energy Balance in Mice with Continuous Glucose Telemetry and Indirect CalorimetryS10OD028635 · OD · BETH ISRAEL DEACONESS MEDICAL CENTER · PI BANKS, ALEXANDER · 2020 to 2020
$737k
Howard Hughes Medical InstituteNHLBI NIH HHS R01 HL160689NIDDK NIH HHS DP1 DK126160NIDDK NIH HHS R01 DK081572NIDDK NIH HHS R01 DK097441NIDDK NIH HHS R01 DK125283NIDDK NIH HHS R01 DK133948NIDDK NIH HHS R01 DK135474NIDDK NIH HHS T32 DK007516NIH HHS S10 OD028635
6 · The paper itself

Abstract

Brown adipose tissue (BAT) is best known for thermogenesis. Rodent studies demonstrated that enhanced BAT thermogenesis is tightly associated with increased energy expenditure, reduced body weight, and improved glucose homeostasis. However, human BAT is protective against type 2 diabetes, independent of body weight. The mechanism underlying this dissociation remains unclear. Here, we report that impaired mitochondrial catabolism of branched-chain amino acids (BCAAs) in BAT, by deleting mitochondrial BCAA carriers (MBCs), caused systemic insulin resistance without affecting energy expenditure and body weight. Brown adipocytes catabolized BCAA in the mitochondria as nitrogen donors for the biosynthesis of non-essential amino acids and glutathione. Impaired mitochondrial BCAA-nitrogen flux in BAT resulted in increased oxidative stress, decreased hepatic insulin signaling, and decreased circulating BCAA-derived metabolites. A high-fat diet attenuated BCAA-nitrogen flux and metabolite synthesis in BAT, whereas cold-activated BAT enhanced the synthesis. This work uncovers a metabolite-mediated pathway through which BAT controls metabolic health beyond thermogenesis.

Indexed as

Adipose Tissue, BrownAmino Acids, Branched-ChainInsulin ResistanceMitochondriaNitrogenThermogenesisAdipocytes, BrownAnimalsDiet, High-FatEnergy MetabolismHumansInsulinMaleMiceMice, Inbred C57BLOxidative StressAmino Acids, Branched-ChainInsulinNitrogenamino acid metabolismbioenergeticsbrown adipose tissuediabetesglucose homeostasisinsulin resistanceinter-organ communicationmitochondriathermogenesis

Identifiers

PMID38653240
PMCPMC11145561
OpenAlexW4394998558

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.