If you have any problems related to the accessibility of any content (or if you want to request that a specific publication be accessible), please contact (firstname.lastname@example.org). We will work to respond to each request in as timely a manner as possible.
Emptying the DUSP Bin: A Role for DUSP5 in Adipose Tissue Inflammation
AdvisorFerguson, Bradley S.
StatisticsView Usage Statistics
Adipose tissue inflammation is a central pathological element that regulates obesity-mediated insulin resistance and type II diabetes. Evidence demonstrates that extracellular signal-regulated kinase 1/2 (ERK 1/2) activation (i.e. phosphorylation) links tumor necrosis factor α (TNFα) to insulin signaling in the cytosol and pro-inflammatory gene expression in the nucleus. Dual specificity phosphatases (DUSPs) inactivate ERK 1/2 through dephosphorylation and can thus inhibit inflammation. We report that DUSP5, an ERK1/2 – specific phosphatase, was induced in white adipose tissue (WAT) in response to diet-induced obesity and that DUSP5 expression increased during obesity development concomitant to increases in TNFα expression. Similar to in vivo observations, DUSP5 expression increased in adipocytes in response to TNFα that was consistent with ERK1/2 dephosphorylation. Based on these findings, we demonstrated that genetic loss of DUSP5 function exacerbated TNFα-mediated ERK 1/2 signaling in 3T3-L1 adipocytes and in adipose tissue of mice. Of note, inhibition of ERK 1/2 and c-Jun N terminal kinase (JNK) signaling attenuated TNFα-induced DUSP5 expression. These data demonstrate that DUSP5 functions in the feedback inhibition of ERK1/2 signaling in response to inflammation and that loss of DUSP5 exacerbates adipose tissue inflammation; suggesting that DUSP5 is an endogenous regulator of adipose tissue inflammation in response to obesity.