Evidence mapPaperPMID 29874587Full record

ArticleCell reports2018

Obesity and Insulin Resistance Promote Atherosclerosis through an IFNγ-Regulated Macrophage Protein Network.

Catherine A Reardon, Amulya Lingaraju, Kelly Q Schoenfelt, Guolin Zhou, Chang Cui, Hannah Jacobs-El, Ilona Babenko, Andrew Hoofnagle, Daniel Czyz, Howard Shuman and 2 more

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed
4.8field-weighted citation impact, top 4% 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

62 citing papers in PubMed, 102 citations in OpenAlex.

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2 more citing papers are in PubMed but not listed here.

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

12 authors at 2 institutions in 1 country.

Catherine A ReardonCommittee on Molecular Metabolism and Nutrition, The University of Chicago, Chicago, IL 60637, USA; Ben May Department for Cancer Research, The University of Chicago, Chicago, IL 60637, USA.
Amulya LingarajuBen May Department for Cancer Research, The University of Chicago, Chicago, IL 60637, USA; Committee on Molecular Pathogenesis and Molecular Medicine, The University of Chicago, Chicago, IL 60637, USA.
Kelly Q SchoenfeltBen May Department for Cancer Research, The University of Chicago, Chicago, IL 60637, USA.
Guolin ZhouBen May Department for Cancer Research, The University of Chicago, Chicago, IL 60637, USA.
Chang CuiBen May Department for Cancer Research, The University of Chicago, Chicago, IL 60637, USA.
Hannah Jacobs-ElBen May Department for Cancer Research, The University of Chicago, Chicago, IL 60637, USA.
Ilona BabenkoDepartment of Medicine, University of Washington, Seattle, WA 98195, USA.
Andrew HoofnagleDepartment of Laboratory Medicine, University of Washington, Seattle, WA 98195, USA.
Daniel CzyzDepartment of Microbiology, The University of Chicago, Chicago, IL 60637, USA.
Howard ShumanDepartment of Microbiology, The University of Chicago, Chicago, IL 60637, USA; Committe on Microbiology, The University of Chicago, Chicago, IL 60637, USA.
Tomas VaisarDepartment of Medicine, University of Washington, Seattle, WA 98195, USA.
Lev BeckerCommittee on Molecular Metabolism and Nutrition, The University of Chicago, Chicago, IL 60637, USA; Ben May Department for Cancer Research, The University of Chicago, Chicago, IL 60637, USA. Electronic address: levb@uchicago.edu.
University of Chicago · USUniversity of Washington · US

Funding

Vector and Transgenic Mouse CoreP30DK017047 · NIDDK · UNIVERSITY OF WASHINGTON · 1986 to 2025
$12.6M
'Metabolically Activated' Macrophages in Obesity and Insulin ResistanceR01DK102960 · NIDDK · UNIVERSITY OF CHICAGO · PI Lev Becker · 2022 to 2024
$1.5M
Physiology CoreP30DK020595 · UNIVERSITY OF CHICAGO · 2025 to 2025
$1.4M
NHLBI NIH HHS R01 HL131028NIDDK NIH HHS P30 DK017047NIDDK NIH HHS P30 DK020595NIDDK NIH HHS R01 DK102960
6 · The paper itself

Abstract

Type 2 diabetes (T2D) is associated with increased risk for atherosclerosis; however, the mechanisms underlying this relationship are poorly understood. Macrophages, which are activated in T2D and causatively linked to atherogenesis, are an attractive mechanistic link. Here, we use proteomics to show that diet-induced obesity and insulin resistance (obesity/IR) modulate a pro-atherogenic "macrophage-sterol-responsive-network" (MSRN), which, in turn, predisposes macrophages to cholesterol accumulation. We identify IFNγ as the mediator of obesity/IR-induced MSRN dysregulation and increased macrophage cholesterol accumulation and show that obesity/IR primes T cells to increase IFNγ production. Accordingly, myeloid cell-specific deletion of the IFNγ receptor (Ifngr1-/-) restores MSRN proteins, attenuates macrophage cholesterol accumulation and atherogenesis, and uncouples the strong relationship between hyperinsulinemia and aortic root lesion size in hypercholesterolemic Ldlr-/- mice with obesity/IR, but does not affect these parameters in Ldlr-/- mice without obesity/IR. Collectively, our findings identify an IFNγ-macrophage pathway as a mechanistic link between obesity/IR and accelerated atherogenesis.

Indexed as

Insulin ResistanceAnimalsAtherosclerosisCholesterolFoam CellsGene Expression RegulationInterferon-gammaInterferon gamma ReceptorMacrophagesMice, Inbred C57BLMice, KnockoutMyeloid CellsObesityReceptors, InterferonReceptors, LDLCholesterolInterferon-gammaInterferon gamma ReceptorReceptors, InterferonReceptors, LDLaltherosclerosischolesterolfoam cellsIFN-gammainsulin resistancemacrophagesobesityproteomicstype 2 diabetes

Identifiers

PMID29874587
PMCPMC6082182
OpenAlexW2806511168

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.