Evidence mapPaperPMID 35917178Full record

ArticleJCI insight2022

The TBK1/IKKε inhibitor amlexanox improves dyslipidemia and prevents atherosclerosis.

Peng Zhao, Xiaoli Sun, Zhongji Liao, Hong Yu, Dan Li, Zeyang Shen, Christopher K Glass, Joseph L Witztum, Alan R Saltiel

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
1.6field-weighted citation impact, top 17% 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

16 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Caspase-6 Controls Lipid and Energy Metabolism in Diet-Induced Obesity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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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

9 authors at 3 institutions in 2 countries.

Peng ZhaoDepartment of Biochemistry and Structural Biology and.
Xiaoli SunMays Cancer Center, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
Zhongji LiaoDepartment of Medicine, University of California, San Diego (UCSD), La Jolla, California, USA.
Hong YuDepartment of Pharmacology and.
Dan LiDepartment of Biochemistry and Structural Biology and.
Zeyang ShenDepartment of Cellular and Molecular Medicine, School of Medicine.
Christopher K GlassDepartment of Medicine, University of California, San Diego (UCSD), La Jolla, California, USA.
Joseph L WitztumDepartment of Medicine, University of California, San Diego (UCSD), La Jolla, California, USA.
Alan R SaltielDepartment of Medicine, University of California, San Diego (UCSD), La Jolla, California, USA.
University of California San Diego · USThe University of Texas Health Science Center at San Antonio · USBioengineering Center · RU

Funding

Pilot & Feasibility ProgramP30DK063491 · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2003 to 2025
$5.4M
U of Calif, San Diego Neuroscience Microscopy ImagingP30NS047101 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JOSEPH G GLEESON, Binhai Zheng · 2003 to 2021
$2.9M
Regulation of glycogen in health and diseaseR01DK117551 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 to 2025
$914k
A novel pathway controls liver injury in NASHR01DK133304 · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2025 to 2025
$519k
NHLBI NIH HHS K99 HL143277NHLBI NIH HHS K99 HL148504NHLBI NIH HHS P01 HL147835NHLBI NIH HHS R00 HL143277NHLBI NIH HHS R00 HL148504NIDDK NIH HHS P30 DK063491NIDDK NIH HHS R01 DK117551NIDDK NIH HHS R01 DK122804NIDDK NIH HHS R01 DK124496NIDDK NIH HHS R01 DK125820NIDDK NIH HHS R01 DK133304NINDS NIH HHS P30 NS047101
6 · The paper itself

Abstract

Cardiovascular diseases, especially atherosclerosis and its complications, are a leading cause of death. Inhibition of the noncanonical IκB kinases TANK-binding kinase 1 and IKKε with amlexanox restores insulin sensitivity and glucose homeostasis in diabetic mice and human patients. Here we report that amlexanox improves diet-induced hypertriglyceridemia and hypercholesterolemia in Western diet-fed (WD-fed) Ldlr-/- mice and protects against atherogenesis. Amlexanox ameliorated dyslipidemia, inflammation, and vascular dysfunction through synergistic actions that involve upregulation of bile acid synthesis to increase cholesterol excretion. Transcriptomic profiling demonstrated an elevated expression of key bile acid synthesis genes. Furthermore, we found that amlexanox attenuated monocytosis, eosinophilia, and vascular dysfunction during WD-induced atherosclerosis. These findings demonstrate the potential of amlexanox as a therapy for hypercholesterolemia and atherosclerosis.

Indexed as

AtherosclerosisDiabetes Mellitus, ExperimentalHypercholesterolemiaAminopyridinesAnimalsBile Acids and SaltsHumansI-kappa B KinaseMiceProtein Serine-Threonine KinasesAminopyridinesamlexanoxBile Acids and SaltsI-kappa B KinaseProtein Serine-Threonine KinasesTBK1 protein, humanTbk1 protein, mouseCardiovascular diseaseCholesterolMetabolism

Identifiers

PMID35917178
PMCPMC9536260
OpenAlexW4289518254

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.