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

Lancaster GI, Kraakman MJ, Kammoun HL, Langley KG, Estevez E, Banerjee A, Grumont RJ, Febbraio MA, Gerondakis S - PLoS ONE (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Cellular and Molecular Metabolism Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.

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 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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HFD increases dusp2 mRNA expression.Dusp2 mRNA expression in the WAT of wt C57Bl6J mice fed either SCD or HFD for 12 weeks. * p<0.05. Data are mean ± SD. N = 5 for SCD and 8 for HFD.
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pone-0111524-g001: HFD increases dusp2 mRNA expression.Dusp2 mRNA expression in the WAT of wt C57Bl6J mice fed either SCD or HFD for 12 weeks. * p<0.05. Data are mean ± SD. N = 5 for SCD and 8 for HFD.

Mentions: DUSP2 expression is markedly increased in many immune cell types following activation [18], [22]. Given activated immune cells accumulate in the adipose tissue of obese mice, we first determined whether dusp2 gene expression was increased in the epididymal WAT of obese mice. Consistent with the links between immune cell dependent inflammation and obesity, dusp2 mRNA expression was significantly higher in WAT from wt mice fed a HFD compared with wt mice fed a SCD (Figure 1).


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

Lancaster GI, Kraakman MJ, Kammoun HL, Langley KG, Estevez E, Banerjee A, Grumont RJ, Febbraio MA, Gerondakis S - PLoS ONE (2014)

HFD increases dusp2 mRNA expression.Dusp2 mRNA expression in the WAT of wt C57Bl6J mice fed either SCD or HFD for 12 weeks. * p<0.05. Data are mean ± SD. N = 5 for SCD and 8 for HFD.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4222916&req=5

pone-0111524-g001: HFD increases dusp2 mRNA expression.Dusp2 mRNA expression in the WAT of wt C57Bl6J mice fed either SCD or HFD for 12 weeks. * p<0.05. Data are mean ± SD. N = 5 for SCD and 8 for HFD.
Mentions: DUSP2 expression is markedly increased in many immune cell types following activation [18], [22]. Given activated immune cells accumulate in the adipose tissue of obese mice, we first determined whether dusp2 gene expression was increased in the epididymal WAT of obese mice. Consistent with the links between immune cell dependent inflammation and obesity, dusp2 mRNA expression was significantly higher in WAT from wt mice fed a HFD compared with wt mice fed a SCD (Figure 1).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Cellular and Molecular Metabolism Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.

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 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.

Show MeSH
Related in: MedlinePlus