The dual-specificity phosphatase 2 (DUSP2) does not regulate obesity-associated inflammation or insulin resistance in mice

Graeme I Lancaster, Michael J Kraakman, H L Kammoun, Katherine G Langley, Emma Estevez, Ashish Banerjee, Raelene Joy Grumont, Mark Anthony Febbraio, Steven Demetrious Gerondakis

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Alterations in the immune cell profile and the induction of inflammation within adipose tissue are a hallmark of obesity in mice and humans. Dual-specificity phosphatase 2 (DUSP2) is widely expressed within the immune system and plays a key role promoting immune and inflammatory responses dependent on mitogen-activated protein kinase (MAPK) activity. We hypothesised that the absence of DUSP2 would protect mice against obesity-associated inflammation and insulin resistance. Accordingly, male and female littermate mice that are either wild-type (wt) or homozygous for a germ-line null mutation of the dusp2 gene (dusp2-/-) were fed either a standard chow diet (SCD) or high fat diet (HFD) for 12 weeks prior to metabolic phenotyping. Compared with mice fed the SCD, all mice consuming the HFD became obese, developed glucose intolerance and insulin resistance, and displayed increased macrophage recruitment and markers of inflammation in epididymal white adipose tissue. The absence of DUSP2, however, had no effect on the development of obesity or adipose tissue inflammation. Whole body insulin sensitivity in male mice was unaffected by an absence of DUSP2 in response to either the SCD or HFD; however, HFD-induced insulin resistance was slightly, but significantly, reduced in female dusp2-/- mice. In conclusion, DUSP2 plays no role in regulating obesity-associated inflammation and only a minor role in controlling insulin sensitivity following HFD in female, but not male, mice. These data indicate that rather than DUSP2 being a pan regulator of MAPK dependent immune cell mediated inflammation, it appears to differentially regulate inflammatory responses that have a MAPK component.
Original languageEnglish
Article numbere111524
Number of pages8
JournalPLoS ONE
Volume9
Issue number11
DOIs
Publication statusPublished - 2014

Cite this

Lancaster, Graeme I ; Kraakman, Michael J ; Kammoun, H L ; Langley, Katherine G ; Estevez, Emma ; Banerjee, Ashish ; Grumont, Raelene Joy ; Febbraio, Mark Anthony ; Gerondakis, Steven Demetrious. / The dual-specificity phosphatase 2 (DUSP2) does not regulate obesity-associated inflammation or insulin resistance in mice. In: PLoS ONE. 2014 ; Vol. 9, No. 11.
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abstract = "Alterations in the immune cell profile and the induction of inflammation within adipose tissue are a hallmark of obesity in mice and humans. Dual-specificity phosphatase 2 (DUSP2) is widely expressed within the immune system and plays a key role promoting immune and inflammatory responses dependent on mitogen-activated protein kinase (MAPK) activity. We hypothesised that the absence of DUSP2 would protect mice against obesity-associated inflammation and insulin resistance. Accordingly, male and female littermate mice that are either wild-type (wt) or homozygous for a germ-line null mutation of the dusp2 gene (dusp2-/-) were fed either a standard chow diet (SCD) or high fat diet (HFD) for 12 weeks prior to metabolic phenotyping. Compared with mice fed the SCD, all mice consuming the HFD became obese, developed glucose intolerance and insulin resistance, and displayed increased macrophage recruitment and markers of inflammation in epididymal white adipose tissue. The absence of DUSP2, however, had no effect on the development of obesity or adipose tissue inflammation. Whole body insulin sensitivity in male mice was unaffected by an absence of DUSP2 in response to either the SCD or HFD; however, HFD-induced insulin resistance was slightly, but significantly, reduced in female dusp2-/- mice. In conclusion, DUSP2 plays no role in regulating obesity-associated inflammation and only a minor role in controlling insulin sensitivity following HFD in female, but not male, mice. These data indicate that rather than DUSP2 being a pan regulator of MAPK dependent immune cell mediated inflammation, it appears to differentially regulate inflammatory responses that have a MAPK component.",
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The dual-specificity phosphatase 2 (DUSP2) does not regulate obesity-associated inflammation or insulin resistance in mice. / Lancaster, Graeme I; Kraakman, Michael J; Kammoun, H L; Langley, Katherine G; Estevez, Emma; Banerjee, Ashish; Grumont, Raelene Joy; Febbraio, Mark Anthony; Gerondakis, Steven Demetrious.

In: PLoS ONE, Vol. 9, No. 11, e111524, 2014.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - The dual-specificity phosphatase 2 (DUSP2) does not regulate obesity-associated inflammation or insulin resistance in mice

AU - Lancaster, Graeme I

AU - Kraakman, Michael J

AU - Kammoun, H L

AU - Langley, Katherine G

AU - Estevez, Emma

AU - Banerjee, Ashish

AU - Grumont, Raelene Joy

AU - Febbraio, Mark Anthony

AU - Gerondakis, Steven Demetrious

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