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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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Related in: MedlinePlus

MAPK analysis in epididymal adipose tissue.JNK (a), ERK (b) and p38 (c) phosphorylation status in epididymal adipose tissue of male mice. ***p<0.005 Main Effect SCD vs. HFD. Data are mean ± SD. White bars are wt mice, black bars are dusp2−/− mice. Ns are 5, 7, 8 and 8 for wt SCD, dusp2−/− SCD, wt HFD and dusp2−/− HFD, respectively.
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pone-0111524-g006: MAPK analysis in epididymal adipose tissue.JNK (a), ERK (b) and p38 (c) phosphorylation status in epididymal adipose tissue of male mice. ***p<0.005 Main Effect SCD vs. HFD. Data are mean ± SD. White bars are wt mice, black bars are dusp2−/− mice. Ns are 5, 7, 8 and 8 for wt SCD, dusp2−/− SCD, wt HFD and dusp2−/− HFD, respectively.

Mentions: The activation of JNK and subsequent serine phosphorylation of insulin receptor substrate 1 (IRS1) in adipose tissue is postulated to be a key nexus by which a number of obesity-associated stimuli can directly impair insulin-dependent signaling [1]. A report that JNK phosphorylation is abnormally elevated in dusp2−/− cells following stimulation [18] prompted us to examine the impact of DUSP2 on JNK activation in epididymal adipose tissue. We observed a significant increase in the level of JNK phosphorylation in the WAT of male mice following 12 weeks of HFD (Figure 6a). However, the absence of DUSP2 had no additional impact on the levels of JNK phosphorylation in WAT (Figure 6a). We also determined ERK1/2 (Figure 6b) and p38 (Figure 6c) phosphorylation levels in WAT by western blotting. Neither the HFD nor DUSP2 deletion affected ERK1/2 or p38 phosphorylation in WAT.


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)

MAPK analysis in epididymal adipose tissue.JNK (a), ERK (b) and p38 (c) phosphorylation status in epididymal adipose tissue of male mice. ***p<0.005 Main Effect SCD vs. HFD. Data are mean ± SD. White bars are wt mice, black bars are dusp2−/− mice. Ns are 5, 7, 8 and 8 for wt SCD, dusp2−/− SCD, wt HFD and dusp2−/− HFD, respectively.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0111524-g006: MAPK analysis in epididymal adipose tissue.JNK (a), ERK (b) and p38 (c) phosphorylation status in epididymal adipose tissue of male mice. ***p<0.005 Main Effect SCD vs. HFD. Data are mean ± SD. White bars are wt mice, black bars are dusp2−/− mice. Ns are 5, 7, 8 and 8 for wt SCD, dusp2−/− SCD, wt HFD and dusp2−/− HFD, respectively.
Mentions: The activation of JNK and subsequent serine phosphorylation of insulin receptor substrate 1 (IRS1) in adipose tissue is postulated to be a key nexus by which a number of obesity-associated stimuli can directly impair insulin-dependent signaling [1]. A report that JNK phosphorylation is abnormally elevated in dusp2−/− cells following stimulation [18] prompted us to examine the impact of DUSP2 on JNK activation in epididymal adipose tissue. We observed a significant increase in the level of JNK phosphorylation in the WAT of male mice following 12 weeks of HFD (Figure 6a). However, the absence of DUSP2 had no additional impact on the levels of JNK phosphorylation in WAT (Figure 6a). We also determined ERK1/2 (Figure 6b) and p38 (Figure 6c) phosphorylation levels in WAT by western blotting. Neither the HFD nor DUSP2 deletion affected ERK1/2 or p38 phosphorylation in WAT.

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