Evidence map›Paper›PMID 29649324›Full record

ArticlePloS one2018

A low dose lipid infusion is sufficient to induce insulin resistance and a pro-inflammatory response in human subjects.

Hanyu Liang, Helen Lum, Andrea Alvarez, Jose de Jesus Garduno-Garcia, Benjamin J Daniel, Nicolas Musi

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

15 citing papers in PubMed, 28 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Article
  4. Article
  5. Review
  6. Article
  7. Review
  8. The Novel Role of Metabolism-Associated Molecular Patterns in Sepsis.Frontiers in cellular and infection microbiology · 2022
    Review
  9. Review
  10. Review
  11. Article
  12. Review
  13. Review
  14. Article
  15. Elevated free fatty acid level is associated with insulin-resistant state in nondiabetic Chinese people.Diabetes, metabolic syndrome and obesity : targets and therapy · 2019
    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

6 authors at 3 institutions in 1 country.

Hanyu LiangBarshop Institute of Longevity and Aging Studies, UT Health San Antonio, San Antonio, Texas, United States of America.ORCID 0000-0002-5893-8750
Helen LumBarshop Institute of Longevity and Aging Studies, UT Health San Antonio, San Antonio, Texas, United States of America.
Andrea AlvarezDepartment of Medicine-Diabetes Division, UT Health San Antonio, San Antonio, Texas, United States of America.
Jose de Jesus Garduno-GarciaDepartment of Medicine-Diabetes Division, UT Health San Antonio, San Antonio, Texas, United States of America.
Benjamin J DanielDepartment of Microbiology, UT Health San Antonio, San Antonio, Texas, United States of America.
Nicolas MusiBarshop Institute of Longevity and Aging Studies, UT Health San Antonio, San Antonio, Texas, United States of America.
Audie L. Murphy Memorial VA Hospital · USThe University of Texas Health Science Center at Houston · USThe University of Texas Health Science Center at San Antonio · US

Funding

TISSUE CULTURE---COREP30CA054174 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Robin Jean Leach · 1991 to 2026
$59.1M
TRANSGENIC COREP30AG013319 · NIA · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI JAMES FLOYD NELSON · 1995 to 2026
$30.6M
Institute for Integration of Medicine & Science: A Partnership to Improve HealthUL1TR001120 · NCATS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI CLARK, ROBERT A, HARGREAVES, KENNETH M · 2013 to 2017
$16.5M
San Antonio OAIC - Research Education Component (REC)P30AG044271 · NIA · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Adam Salmon · 2015 to 2026
$14.1M
Institute for Integration of Medicine & Science: A Partnership to Improve HealthUL1TR000149 · NCATS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI CLARK, ROBERT A · 2012 to 2013
$6.8M
Role of TLR4 on insulin resistance in humansR01DK080157 · NIDDK · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI MUSI, NICOLAS · 2008 to 2017
$3.0M
Effect of age on glucose and lipid metabolismR01DK089229 · NIDDK · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI MUSI, NICOLAS · 2010 to 2013
$1.3M
NCATS NIH HHS UL1 TR000149NCATS NIH HHS UL1 TR001120NCI NIH HHS P30 CA054174NIA NIH HHS P30 AG013319NIA NIH HHS P30 AG044271NIDDK NIH HHS AG013319NIDDK NIH HHS P30 AG044271NIDDK NIH HHS R01 DK080157NIDDK NIH HHS R01 DK089229NIDDK NIH HHS R01-DK089229NIDDK NIH HHS R01-DK80157NIDDK NIH HHS UL1TR000149
6 · The paper itself

Abstract

objectiveThe root cause behind the low-grade inflammatory state seen in insulin resistant (obesity and type 2 diabetes) states is unclear. Insulin resistant subjects have elevations in plasma free fatty acids (FFA), which are ligands for the pro-inflammatory toll-like receptor (TLR)4 pathway. We tested the hypothesis that an experimental elevation in plasma FFA (within physiological levels) in lean individuals would upregulate TLR4 and activate downstream pathways (e.g., MAPK) in circulating monocytes. RESEARCH DESIGN AND

methodsTwelve lean, normal glucose-tolerant subjects received a low dose (30 ml/h) 48 h lipid or saline infusion on two different occasions. Monocyte TLR4 protein level, MAPK phosphorylation, and expression of genes in the TLR pathway were determined before and after each infusion.

resultsThe lipid infusion significantly increased monocyte TLR4 protein and phosphorylation of JNK and p38 MAPK. Lipid-mediated increases in TLR4 and p38 phosphorylation directly correlated with reduced peripheral insulin sensitivity (M value). Lipid increased levels of multiple genes linked to inflammation, including several TLRs, CD180, MAP3K7, and CXCL10. Monocytes exposed in vivo to lipid infusion exhibited enhanced in vitro basal and LPS-stimulated IL-1β secretion.

conclusionsIn lean subjects, a small increase in plasma FFA (as seen in insulin resistant subjects) is sufficient to upregulate TLR4 and stimulate inflammatory pathways (MAPK) in monocytes. Moreover, lipids prime monocytes to endotoxin. We provide proof-of-concept data in humans indicating that the low-grade inflammatory state characteristic of obesity and type 2 diabetes could be caused (at least partially) by pro-inflammatory monocytes activated by excess lipids present in these individuals.

Indexed as

Insulin ResistanceBiomarkersCytokinesFemaleGene ExpressionGene Expression ProfilingGlucoseHumansInflammationInsulinLipidsMaleMitogen-Activated Protein KinasesMonocytesToll-Like ReceptorsBiomarkersCytokinesGlucoseInsulinLipidsMitogen-Activated Protein KinasesToll-Like Receptors

Identifiers

PMID29649324
PMCPMC5897027
OpenAlexW2797273936

What OpenQuestion holds

Textmetadata
LicenceCC0
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 OpenQuestion graph.