Evidence map›Paper›PMID 25754609›Full record

ArticleNature communications2015

Brown fat activation reduces hypercholesterolaemia and protects from atherosclerosis development.

Jimmy F P Berbée, Mariëtte R Boon, P Padmini S J Khedoe, Alexander Bartelt, Christian Schlein, Anna Worthmann, Sander Kooijman, Geerte Hoeke, Isabel M Mol, Clara John and 10 more

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

Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03793127 (BAT as a Therapeutic for the Metabolic and Cardiac Dysfunction With Senescence Pilot), which is not on this map. Cited by 243 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
243citing papers in PubMed, 1 pooled it
23.6field-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.

NCT03793127 active not recruitingnot on this mapstarted 2019, after this paper: background citation

BAT as a Therapeutic for the Metabolic and Cardiac Dysfunction With Senescence Pilot

TypeobservationalSponsorAdventHealth Translational Research InstituteRan2019 to 2025Enrolled24ConditionsAgingArmsMaximal oxygen consumption (V02 max), Brown adipose tissue (BAT) imaging, Muscle function testing
3 · Its place in the literature

Who cites it

243 citing papers in PubMed, 1 synthesis or guideline pooled it, 427 citations in OpenAlex.

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  16. Junctophilin-2-orchestrated calcium signalosome regulates brown adipocyte thermogenesis and energy metabolism.Proceedings of the National Academy of Sciences of the United States of America · 2026
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183 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 4 institutions in 3 countries.

Jimmy F P Berbée1] Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands [2] Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands.
Mariëtte R Boon1] Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands [2] Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands.
P Padmini S J Khedoe1] Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands [2] Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands [3] Department of Pulmonology, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands.
Alexander Bartelt1] Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, Hamburg 20246, Germany [2] Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Christian SchleinDepartment of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, Hamburg 20246, Germany.
Anna WorthmannDepartment of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, Hamburg 20246, Germany.
Sander Kooijman1] Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands [2] Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands.
Geerte Hoeke1] Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands [2] Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands.
Isabel M Mol1] Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands [2] Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands.
Clara JohnDepartment of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, Hamburg 20246, Germany.
Caroline JungDiagnostic and Interventional Radiology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, Hamburg 20246, Germany.
Nadia Vazirpanah1] Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands [2] Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands.
Linda P J Brouwers1] Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands [2] Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands.
Philip L S M GordtsDepartment of Cellular and Molecular Medicine, University of California-San Diego, La Jolla, California 92093, USA.
Jeffrey D EskoDepartment of Cellular and Molecular Medicine, University of California-San Diego, La Jolla, California 92093, USA.
Pieter S HiemstraDepartment of Pulmonology, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands.
Louis M Havekes1] Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands [2] Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands [3] Department of Cardiology, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands [4] Netherlands Organization for Applied Scientific Research-Metabolic Health Research, Gaubius Laboratory, Zernikedreef 9, Leiden 2333 CK, The Netherlands.
Ludger SchejaDepartment of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, Hamburg 20246, Germany.
Joerg HeerenDepartment of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, Hamburg 20246, Germany.
Patrick C N Rensen1] Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands [2] Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands.
Leiden University Medical Center · NLUniversität Hamburg · DEUniversity Medical Center Hamburg-Eppendorf · DEUniversity of California, San Diego · US

Funding

Siglec Modulation of Inflammatory ResponsesP01HL107150 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LE, DZUNG T · 2011 to 2017
$18.0M
GENETIC CONTROL OF PROTEOGLYCAN METABOLISMR37GM033063 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ESKO, JEFFREY D · 2000 to 2010
$3.9M
LIPID METABOLISM IN ANIMAL CELLSR01GM033063 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ESKO, JEFFREY D · 1985 to 2019
$3.4M
NHLBI NIH HHS P01 HL107150NIGMS NIH HHS GM33063NIGMS NIH HHS R01 GM033063NIGMS NIH HHS R37 GM033063
6 · The paper itself

Abstract

Brown adipose tissue (BAT) combusts high amounts of fatty acids, thereby lowering plasma triglyceride levels and reducing obesity. However, the precise role of BAT in plasma cholesterol metabolism and atherosclerosis development remains unclear. Here we show that BAT activation by β3-adrenergic receptor stimulation protects from atherosclerosis in hyperlipidemic APOE*3-Leiden.CETP mice, a well-established model for human-like lipoprotein metabolism that unlike hyperlipidemic Apoe(-/-) and Ldlr(-/-) mice expresses functional apoE and LDLR. BAT activation increases energy expenditure and decreases plasma triglyceride and cholesterol levels. Mechanistically, we demonstrate that BAT activation enhances the selective uptake of fatty acids from triglyceride-rich lipoproteins into BAT, subsequently accelerating the hepatic clearance of the cholesterol-enriched remnants. These effects depend on a functional hepatic apoE-LDLR clearance pathway as BAT activation in Apoe(-/-) and Ldlr(-/-) mice does not attenuate hypercholesterolaemia and atherosclerosis. We conclude that activation of BAT is a powerful therapeutic avenue to ameliorate hyperlipidaemia and protect from atherosclerosis.

Indexed as

Cold TemperatureAcclimatizationAdipose Tissue, BrownAnimalsApolipoproteins EAtherosclerosisCalorimetry, IndirectCholesterolFemaleHypercholesterolemiaLiverMaleMiceMice, KnockoutReceptors, Adrenergic, beta-3Receptors, LDLApolipoproteins ECholesterolReceptors, Adrenergic, beta-3Receptors, LDLTriglycerides

Identifiers

PMID25754609
PMCPMC4366535
OpenAlexW2032149290

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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.