Evidence map›Paper›PMID 25706874›Full record

ArticleNature medicine2015

LTB4 promotes insulin resistance in obese mice by acting on macrophages, hepatocytes and myocytes.

Pingping Li, Da Young Oh, Gautam Bandyopadhyay, William S Lagakos, Saswata Talukdar, Olivia Osborn, Andrew Johnson, Heekyung Chung, Michael Maris, Jachelle M Ofrecio and 3 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 181 papers.

0numbers the graph read from it
0cells of the map it votes in
181citing papers in PubMed
14.9field-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

181 citing papers in PubMed, 311 citations in OpenAlex.

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  14. Plasma leukotriene BDiabetes, obesity & metabolism · 2025
    Article
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121 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 2 institutions in 3 countries.

Pingping Li *Division of Endocrinology & Metabolism, Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, USA, 92093.
Da Young Oh *Division of Endocrinology & Metabolism, Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, USA, 92093.
Gautam BandyopadhyayDivision of Endocrinology & Metabolism, Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, USA, 92093.
William S LagakosDivision of Endocrinology & Metabolism, Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, USA, 92093.
Saswata TalukdarDivision of Endocrinology & Metabolism, Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, USA, 92093.
Olivia OsbornDivision of Endocrinology & Metabolism, Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, USA, 92093.
Andrew JohnsonDivision of Endocrinology & Metabolism, Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, USA, 92093.
Heekyung ChungDivision of Endocrinology & Metabolism, Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, USA, 92093.
Michael MarisDivision of Endocrinology & Metabolism, Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, USA, 92093.
Jachelle M OfrecioDivision of Endocrinology & Metabolism, Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, USA, 92093.
Sayaka TaguchiDivision of Endocrinology & Metabolism, Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, USA, 92093.
Min LuDivision of Endocrinology & Metabolism, Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, USA, 92093.
Jerrold M OlefskyDivision of Endocrinology & Metabolism, Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, USA, 92093.
Executive Office of the President · USAcademy of Medical Sciences · GB

Funding

Transgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Andrea L Hevener · 2003 to 2026
$40.4M
Transcriptional Genomics CoreP01DK074868 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLASS, CHRISTOPHER K · 2007 to 2016
$16.6M
The Role of FSH in Female InfertilityP50HD012303 · NICHD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LAWSON, MARK ANDREW · 1985 to 2020
$7.5M
INSULIN RECEPTORS AND THE GLUCOSE TRANSPORT SYSTEMR37DK033651 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI OLEFSKY, JERROLD MICHAEL · 2000 to 2010
$6.1M
INSULIN RECEPTORS AND THE GLUCOSE TRANSPORT SYSTEMR01DK033651 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI OLEFSKY, JERROLD MICHAEL · 1986 to 2013
$2.2M
Molecular Mechanisms of Inflammation, Steatosis and Hepatic Insulin ResistanceR24DK090962 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI OLEFSKY, JERROLD MICHAEL · 2010 to 2011
$1.5M
PHOSPHOCALMODULIN AND INSULIN ACTIONF32DK009062 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI JOYAL, JOHN LOUIS · 1994 to 1996
–
NICHD NIH HHS P50 HD012303NIDDK NIH HHS DK033651NIDDK NIH HHS DK063491NIDDK NIH HHS DK074868NIDDK NIH HHS DK09062NIDDK NIH HHS F32 DK009062NIDDK NIH HHS P01 DK074868NIDDK NIH HHS P30 DK063491NIDDK NIH HHS R01 DK033651NIDDK NIH HHS R24 DK090962NIDDK NIH HHS R37 DK033651
6 · The paper itself

Abstract

Insulin resistance results from several pathophysiologic mechanisms, including chronic tissue inflammation and defective insulin signaling. We found that liver, muscle and adipose tissue exhibit higher levels of the chemotactic eicosanoid LTB4 in obese high-fat diet (HFD)-fed mice. Inhibition of the LTB4 receptor Ltb4r1, through either genetic or pharmacologic loss of function, led to an anti-inflammatory phenotype with protection from insulin resistance and hepatic steatosis. In vitro treatment with LTB4 directly enhanced macrophage chemotaxis, stimulated inflammatory pathways, reduced insulin-stimulated glucose uptake in L6 myocytes, and impaired insulin-mediated suppression of hepatic glucose output in primary mouse hepatocytes. This was accompanied by lower insulin-stimulated Akt phosphorylation and higher Irs-1/2 serine phosphorylation, and all of these events were dependent on Gαi and Jnk1, two downstream mediators of Ltb4r1 signaling. These observations elucidate a novel role of the LTB4-Ltb4r1 signaling pathway in hepatocyte and myocyte insulin resistance, and they show that in vivo inhibition of Ltb4r1 leads to robust insulin-sensitizing effects.

Indexed as

AnimalsBlood GlucoseDiet, High-FatFatty LiverHepatocytesInflammationInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceLeukotriene B4MacrophagesMiceMice, ObeseMuscle Fibers, SkeletalObesityPhosphorylationBlood GlucoseInsulinInsulin Receptor Substrate ProteinsIrs1 protein, mouseIrs2 protein, mouseLeukotriene B4Ltb4r1 protein, mouseProto-Oncogene Proteins c-aktReceptors, Leukotriene B4

Identifiers

PMID25706874
PMCPMC4429798
OpenAlexW2009243735

What OpenQuestion holds

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Registered trials

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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.