The dual-specificity phosphatase 2 (DUSP2) does not regulate obesity-associated inflammation or insulin resistance in mice.
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.
Cellular and Molecular Metabolism Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
Graeme I
GI
Lancaster
Cellular and Molecular Metabolism Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
Michael J
MJ
Kraakman
Cellular and Molecular Metabolism Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
Helene L
HL
Kammoun
Cellular and Molecular Metabolism Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
Katherine G
KG
Langley
Cellular and Molecular Metabolism Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
Emma
E
Estevez
Centre for Cancer Research, MIMR-PHI Institute of Medical Research, Monash University, Victoria, Australia.
Ashish
A
Banerjee
The Australian Centre for Blood Diseases and Department of Clinical Hematology, Monash University Central Clinical School, Melbourne, Victoria, Australia.
Raelene J
RJ
Grumont
Cellular and Molecular Metabolism Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
Mark A
MA
Febbraio
The Australian Centre for Blood Diseases and Department of Clinical Hematology, Monash University Central Clinical School, Melbourne, Victoria, Australia.
Steve
S
Gerondakis
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D059305:Diet, High-Fat; D054641:Dual Specificity Phosphatase 2 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D018149:Glucose Intolerance / Q000235:genetics* / Q000378:metabolism; D005951:Glucose Tolerance Test; D007249:Inflammation / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D051379:Mice; D009154:Mutation; D009765:Obesity / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D012737:Sex Factors
D001786:Blood Glucose; D007328:Insulin; D054641:Dual Specificity Phosphatase 2; C517033:Dusp2 protein, mouse