Interleukin-1 receptor-associated kinase-3 is a key inhibitor of inflammation in obesity and metabolic syndrome.
<h4>Background</h4>Visceral obesity is associated with the rising incidence of type 2 diabetes and metabolic syndrome. Low-grade chronic inflammation and oxidative stress synergize in obesity and obesity-induced disorders.<h4>Objective</h4>We searched a cluster of molecules t...
Guardado en:
| Autores principales: | , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2012
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/7955218849234fcdac25ac8ae6965167 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:7955218849234fcdac25ac8ae6965167 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:7955218849234fcdac25ac8ae69651672021-11-18T07:30:03ZInterleukin-1 receptor-associated kinase-3 is a key inhibitor of inflammation in obesity and metabolic syndrome.1932-620310.1371/journal.pone.0030414https://doaj.org/article/7955218849234fcdac25ac8ae69651672012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22272346/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Visceral obesity is associated with the rising incidence of type 2 diabetes and metabolic syndrome. Low-grade chronic inflammation and oxidative stress synergize in obesity and obesity-induced disorders.<h4>Objective</h4>We searched a cluster of molecules that support interactions between these stress conditions in monocytes.<h4>Methods</h4>RNA expressions in blood monocytes of two independent cohorts comprising 21 and 102 obese persons and 46 age-matched controls were determined by microarray and independently validated by quantitative RT-PCR analysis. The effect of three-month weight loss after bariatric surgery was determined. The effect of RNA silencing on inflammation and oxidative stress was studied in human monocytic THP-1 cells.<h4>Results</h4>Interleukin-1 receptor-associated kinase-3 (IRAK3), key inhibitor of IRAK/NFκB-mediated chronic inflammation, is downregulated in monocytes of obese persons. Low IRAK3 was associated with high superoxide dismutase-2 (SOD2), a marker of mitochondrial oxidative stress. A comparable expression profile was also detected in visceral adipose tissue of the same obese subjects. Low IRAK3 and high SOD2 was associated with a high prevalence of metabolic syndrome (odds ratio: 9.3; sensitivity: 91%; specificity: 77%). By comparison, the odds ratio of high-sensitivity C-reactive protein, a widely used marker of systemic inflammation, was 4.3 (sensitivity: 69%; specificity: 66%). Weight loss was associated with an increase in IRAK3 and a decrease in SOD2, in association with a lowering of systemic inflammation and a decreasing number of metabolic syndrome components. We identified the increase in reactive oxygen species in combination with obesity-associated low adiponectin and high glucose and interleukin-6 as cause of the decrease in IRAK3 in THP-1 cells in vitro.<h4>Conclusion</h4>IRAK3 is a key inhibitor of inflammation in association with obesity and metabolic syndrome. Our data warrant further evaluation of IRAK3 as a diagnostic and prognostic marker, and as a target for intervention.Maarten HulsmansBenjamine GeeraertDieuwke De KeyzerAnn MertensMatthias LannooBart VanaudenaerdeMarc HoylaertsNora BenhabilèsChristos TsatsanisChantal MathieuPaul HolvoetPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 1, p e30414 (2012) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Maarten Hulsmans Benjamine Geeraert Dieuwke De Keyzer Ann Mertens Matthias Lannoo Bart Vanaudenaerde Marc Hoylaerts Nora Benhabilès Christos Tsatsanis Chantal Mathieu Paul Holvoet Interleukin-1 receptor-associated kinase-3 is a key inhibitor of inflammation in obesity and metabolic syndrome. |
| description |
<h4>Background</h4>Visceral obesity is associated with the rising incidence of type 2 diabetes and metabolic syndrome. Low-grade chronic inflammation and oxidative stress synergize in obesity and obesity-induced disorders.<h4>Objective</h4>We searched a cluster of molecules that support interactions between these stress conditions in monocytes.<h4>Methods</h4>RNA expressions in blood monocytes of two independent cohorts comprising 21 and 102 obese persons and 46 age-matched controls were determined by microarray and independently validated by quantitative RT-PCR analysis. The effect of three-month weight loss after bariatric surgery was determined. The effect of RNA silencing on inflammation and oxidative stress was studied in human monocytic THP-1 cells.<h4>Results</h4>Interleukin-1 receptor-associated kinase-3 (IRAK3), key inhibitor of IRAK/NFκB-mediated chronic inflammation, is downregulated in monocytes of obese persons. Low IRAK3 was associated with high superoxide dismutase-2 (SOD2), a marker of mitochondrial oxidative stress. A comparable expression profile was also detected in visceral adipose tissue of the same obese subjects. Low IRAK3 and high SOD2 was associated with a high prevalence of metabolic syndrome (odds ratio: 9.3; sensitivity: 91%; specificity: 77%). By comparison, the odds ratio of high-sensitivity C-reactive protein, a widely used marker of systemic inflammation, was 4.3 (sensitivity: 69%; specificity: 66%). Weight loss was associated with an increase in IRAK3 and a decrease in SOD2, in association with a lowering of systemic inflammation and a decreasing number of metabolic syndrome components. We identified the increase in reactive oxygen species in combination with obesity-associated low adiponectin and high glucose and interleukin-6 as cause of the decrease in IRAK3 in THP-1 cells in vitro.<h4>Conclusion</h4>IRAK3 is a key inhibitor of inflammation in association with obesity and metabolic syndrome. Our data warrant further evaluation of IRAK3 as a diagnostic and prognostic marker, and as a target for intervention. |
| format |
article |
| author |
Maarten Hulsmans Benjamine Geeraert Dieuwke De Keyzer Ann Mertens Matthias Lannoo Bart Vanaudenaerde Marc Hoylaerts Nora Benhabilès Christos Tsatsanis Chantal Mathieu Paul Holvoet |
| author_facet |
Maarten Hulsmans Benjamine Geeraert Dieuwke De Keyzer Ann Mertens Matthias Lannoo Bart Vanaudenaerde Marc Hoylaerts Nora Benhabilès Christos Tsatsanis Chantal Mathieu Paul Holvoet |
| author_sort |
Maarten Hulsmans |
| title |
Interleukin-1 receptor-associated kinase-3 is a key inhibitor of inflammation in obesity and metabolic syndrome. |
| title_short |
Interleukin-1 receptor-associated kinase-3 is a key inhibitor of inflammation in obesity and metabolic syndrome. |
| title_full |
Interleukin-1 receptor-associated kinase-3 is a key inhibitor of inflammation in obesity and metabolic syndrome. |
| title_fullStr |
Interleukin-1 receptor-associated kinase-3 is a key inhibitor of inflammation in obesity and metabolic syndrome. |
| title_full_unstemmed |
Interleukin-1 receptor-associated kinase-3 is a key inhibitor of inflammation in obesity and metabolic syndrome. |
| title_sort |
interleukin-1 receptor-associated kinase-3 is a key inhibitor of inflammation in obesity and metabolic syndrome. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2012 |
| url |
https://doaj.org/article/7955218849234fcdac25ac8ae6965167 |
| work_keys_str_mv |
AT maartenhulsmans interleukin1receptorassociatedkinase3isakeyinhibitorofinflammationinobesityandmetabolicsyndrome AT benjaminegeeraert interleukin1receptorassociatedkinase3isakeyinhibitorofinflammationinobesityandmetabolicsyndrome AT dieuwkedekeyzer interleukin1receptorassociatedkinase3isakeyinhibitorofinflammationinobesityandmetabolicsyndrome AT annmertens interleukin1receptorassociatedkinase3isakeyinhibitorofinflammationinobesityandmetabolicsyndrome AT matthiaslannoo interleukin1receptorassociatedkinase3isakeyinhibitorofinflammationinobesityandmetabolicsyndrome AT bartvanaudenaerde interleukin1receptorassociatedkinase3isakeyinhibitorofinflammationinobesityandmetabolicsyndrome AT marchoylaerts interleukin1receptorassociatedkinase3isakeyinhibitorofinflammationinobesityandmetabolicsyndrome AT norabenhabiles interleukin1receptorassociatedkinase3isakeyinhibitorofinflammationinobesityandmetabolicsyndrome AT christostsatsanis interleukin1receptorassociatedkinase3isakeyinhibitorofinflammationinobesityandmetabolicsyndrome AT chantalmathieu interleukin1receptorassociatedkinase3isakeyinhibitorofinflammationinobesityandmetabolicsyndrome AT paulholvoet interleukin1receptorassociatedkinase3isakeyinhibitorofinflammationinobesityandmetabolicsyndrome |
| _version_ |
1718423351990419456 |