Faculty Collaboration Database

DUSP5 functions as a feedback regulator of TNFα-induced ERK1/2 dephosphorylation and inflammatory gene expression in adipocytes. Sci Rep 2017 Oct 10;7(1):12879

Date

10/12/2017

Pubmed ID

29018280

Pubmed Central ID

PMC5635013

DOI

10.1038/s41598-017-12861-y

Scopus ID

2-s2.0-85030997754 (requires institutional sign-in at Scopus site)   25 Citations

Abstract

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 (ERK 1/2) activation (i.e. phosphorylation) links tumor necrosis factor α (TNFα) to pro-inflammatory gene expression in the nucleus. Dual specificity phosphatases (DUSPs) inactivate ERK 1/2 through dephosphorylation and can thus inhibit inflammatory gene expression. We report that DUSP5, an ERK1/2 phosphatase, was induced in epididymal white adipose tissue (WAT) in response to diet-induced obesity. Moreover, DUSP5 mRNA expression increased during obesity development concomitant to increases in TNFα expression. Consistent with in vivo findings, DUSP5 mRNA expression increased in adipocytes in response to TNFα, parallel with ERK1/2 dephosphorylation. Genetic loss of DUSP5 exacerbated TNFα-mediated ERK 1/2 signaling in 3T3-L1 adipocytes and in adipose tissue of mice. Furthermore, inhibition of ERK 1/2 and c-Jun N terminal kinase (JNK) signaling attenuated TNFα-induced DUSP5 expression. These data suggest that DUSP5 functions in the feedback inhibition of ERK1/2 signaling in response to TNFα, which resulted in increased inflammatory gene expression. Thus, DUSP5 potentially acts as an endogenous regulator of adipose tissue inflammation; although its role in obesity-mediated inflammation and insulin signaling remains unclear.

Author List

Habibian JS, Jefic M, Bagchi RA, Lane RH, McKnight RA, McKinsey TA, Morrison RF, Ferguson BS

MESH terms used to index this publication - Major topics in bold

3T3-L1 Cells
Adipocytes
Animals
Diet, High-Fat
Dual-Specificity Phosphatases
Extracellular Signal-Regulated MAP Kinases
Feedback, Physiological
Gene Deletion
Gene Expression Regulation
Inflammation
Male
Mice
Mice, Inbred C57BL
Obesity
Phosphorylation
RNA, Messenger
Tumor Necrosis Factor-alpha