Evidence map›Paper›PMID 22287546›Full record

ArticleThe Journal of biological chemistry2012

NADPH oxidase-derived reactive oxygen species increases expression of monocyte chemotactic factor genes in cultured adipocytes.

Chang Yeop Han, Tomio Umemoto, Mohamed Omer, Laura J Den Hartigh, Tsuyoshi Chiba, Renee LeBoeuf, Carolyn L Buller, Ian R Sweet, Subramaniam Pennathur, E Dale Abel and 1 more

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.

0numbers the graph read from it
0cells of the map it votes in
97citing papers in PubMed
5.2field-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

97 citing papers in PubMed, 182 citations in OpenAlex.

  1. Review
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  9. Overexpression of adipose tissue ERα enhances PVAT anticontractility via NOX4-derived HAmerican journal of physiology. Heart and circulatory physiology · 2025
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37 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

11 authors at 3 institutions in 1 country.

Chang Yeop HanDivision of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington, Seattle, Washington 98195-6426; Diabetes and Obesity Center of Excellence, University of Washington, Seattle, Washington 98195-6426.
Tomio UmemotoDivision of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington, Seattle, Washington 98195-6426; Diabetes and Obesity Center of Excellence, University of Washington, Seattle, Washington 98195-6426.
Mohamed OmerDivision of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington, Seattle, Washington 98195-6426; Diabetes and Obesity Center of Excellence, University of Washington, Seattle, Washington 98195-6426.
Laura J Den HartighDivision of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington, Seattle, Washington 98195-6426; Diabetes and Obesity Center of Excellence, University of Washington, Seattle, Washington 98195-6426.
Tsuyoshi ChibaDivision of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington, Seattle, Washington 98195-6426; Diabetes and Obesity Center of Excellence, University of Washington, Seattle, Washington 98195-6426.
Renee LeBoeufDivision of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington, Seattle, Washington 98195-6426; Diabetes and Obesity Center of Excellence, University of Washington, Seattle, Washington 98195-6426.
Carolyn L BullerDivision of Nephrology, Department of Medicine, University of Michigan, Ann Arbor, Michigan 48105.
Ian R SweetDivision of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington, Seattle, Washington 98195-6426; Diabetes and Obesity Center of Excellence, University of Washington, Seattle, Washington 98195-6426.
Subramaniam PennathurDivision of Nephrology, Department of Medicine, University of Michigan, Ann Arbor, Michigan 48105.
E Dale AbelDivision of Endocrinology, Metabolism and Diabetes and the Program in Molecular Medicine, University of Utah School of Medicine, Salt Lake City, Utah 84112, and.
Alan ChaitDivision of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington, Seattle, Washington 98195-6426; Diabetes and Obesity Center of Excellence, University of Washington, Seattle, Washington 98195-6426,. Electronic address: achait@u.washington.edu.
University of Washington · USUniversity of Michigan–Ann Arbor · USUniversity of Utah · US

Funding

Vector and Transgenic Mouse CoreP30DK017047 · NIDDK · UNIVERSITY OF WASHINGTON · PI Sakeneh Zraika · 1986 to 2026
$41.4M
PILOT STUDY--CLINICAL NUTRITION RESEARCHP30DK035816 · NIDDK · UNIVERSITY OF WASHINGTON · PI Ellen A Schur · 1986 to 2026
$30.4M
Regional Pilot And Feasibility Study Grants ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Mehboob A Hussain · 2013 to 2026
$24.3M
Pilot and Feasibility (P and F) ProgramP30DK089503 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Joyce Lee · 2010 to 2026
$20.3M
Integrated Systems Biology Approach to Diabetic Microvascular ComplicationsR24DK082841 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ABCOUWER, STEVEN F, BROSIUS, FRANK C · 2008 to 2020
$13.1M
Effect of Nutritional Factors on Macrophage Accumulation in Adipose TissueR01HL094352 · NHLBI · UNIVERSITY OF WASHINGTON · PI CHAIT, ALAN · 2009 to 2012
$1.7M
Genetic Predisposition for Intimal Hyperplasia in MiceR01HL098227 · NHLBI · UNIVERSITY OF WASHINGTON · PI LEBOEUF, RENEE C · 2010 to 2013
$1.6M
Insulin Signaling and the Heart in DiabetesR01DK092065 · NIDDK · UNIVERSITY OF UTAH · PI ABEL, E DALE · 2010 to 2011
$649k
Effect of Dietary Fatty Acids on Adipose Tissue InflammationR56HL094352 · NHLBI · UNIVERSITY OF WASHINGTON · PI CHAIT, ALAN · 2014 to 2014
$435k
NHLBI NIH HHS HL-094352NHLBI NIH HHS R01 HL094352NHLBI NIH HHS R01 HL098227NHLBI NIH HHS R56 HL094352NIDDK NIH HHS DK-082841NIDDK NIH HHS DK-089503NIDDK NIH HHS DK092065NIDDK NIH HHS DK-17047NIDDK NIH HHS P30 DK017047NIDDK NIH HHS P30 DK020572NIDDK NIH HHS P30 DK035816NIDDK NIH HHS P30-DK-035816NIDDK NIH HHS P30 DK089503NIDDK NIH HHS R24 DK082841
6 · The paper itself

Abstract

Excess glucose and free fatty acids delivered to adipose tissue causes local inflammation, which contributes to insulin resistance. Glucose and palmitate generate reactive oxygen species (ROS) in adipocytes, leading to monocyte chemotactic factor gene expression. Docosahexaenoate (DHA) has the opposite effect. In this study, we evaluated the potential sources of ROS in the presence of excess nutrients. Differentiated 3T3-L1 adipocytes were exposed to palmitate and DHA (250 μM) in either 5 or 25 mM glucose to evaluate the relative roles of mitochondrial electron transport and NADPH oxidases (NOX) as sources of ROS. Excess glucose and palmitate did not increase mitochondrial oxidative phosphorylation. However, glucose exposure increased glycolysis. Of the NOX family members, only NOX4 was expressed in adipocytes. Moreover, its activity was increased by excess glucose and palmitate and decreased by DHA. Silencing NOX4 inhibited palmitate- and glucose-stimulated ROS generation and monocyte chemotactic factor gene expression. NADPH, a substrate for NOX, and pentose phosphate pathway activity increased with glucose but not palmitate and decreased with DHA exposure. Inhibition of the pentose phosphate pathway by glucose-6-phosphate dehydrogenase inhibitors and siRNA suppressed ROS generation and monocyte chemotactic factor gene expression induced by both glucose and palmitate. Finally, both high glucose and palmitate induced NOX4 translocation into lipid rafts, effects that were blocked by DHA. Excess glucose and palmitate generate ROS via NOX4 rather than by mitochondrial oxidation in cultured adipocytes. NOX4 is regulated by both NADPH generated in the PPP and translocation of NOX4 into lipid rafts, leading to expression of monocyte chemotactic factors.

Indexed as

3T3-L1 CellsAdipocytesAnimalsDocosahexaenoic AcidsEnzyme InhibitorsGlucoseMembrane MicrodomainsMiceMitochondriaMonocyte Chemoattractant ProteinsNADPH Oxidase 4NADPH OxidasesPalmitic AcidPentose Phosphate PathwayProtein TransportReactive Oxygen SpeciesDocosahexaenoic AcidsEnzyme InhibitorsGlucoseMonocyte Chemoattractant ProteinsNADPH Oxidase 4NADPH OxidasesNox4 protein, mousePalmitic AcidReactive Oxygen SpeciesSweetening Agents

Identifiers

PMID22287546
PMCPMC3322984
OpenAlexW2017814607

What OpenQuestion holds

Textmetadata
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.