Map kinase phosphatase dusp1 is overexpressed in obese humans and modulated by physical exercise

Abdelkrim Khadir, Ali Tiss, Jehad Abubaker, Mohamed Abu-Farha, Irina Al khairi, Preethi Cherian, Jeena John, Sina Kavalakatt, Samia Warsame, Ashraf Al Madhoun, Fahad Al-Ghimlas, Naser Elkum, Kazem Behbehani, Said Dermime, Mohammed Dehbi

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Chronic low-grade inflammation and dysregulation of the stress defense system are cardinal features of obesity, a major risk factor for the development of insulin resistance and diabetes. Dual-specificity protein phosphatase 1 (DUSP1), known also as MAP kinase phosphatase 1 (MKP1), is implicated in metabolism and energy expenditure. Mice lacking DUSP1 are resistant to high-fat diet-induced obesity. However, the expression of DUSP1 has not been investigated in human obesity. In the current study, we compared the expression pattern of DUSP1 between lean and obese nondiabetic human subjects using subcutaneous adipose tissue (SAT) and peripheral blood mononuclear cells (PBMCs). The levels of DUSP1 mRNA and protein were significantly increased in obese subjects with concomitant decrease in the phos-phorylation of p38 MAPK (p-p38 MAPK) and PGC-1α and an increase in the levels of phospho-JNK (p-JNK) and phospho-ERK (p-ERK). Moreover, obese subjects had higher levels of circulating DUSP1 protein that correlated positively with various obesity indicators, triglycerides, glucagon, insulin, leptin, and PAI-1 (P < 0.05) but negatively with Vo2max and high-density lipoprotein (P < 0.05). The observation that DUSP1 was overexpressed in obese subjects prompted us to investigate whether physical exercise could reduce its expression. In this study, we report for the first time that physical exercise significantly attenuated the expression of DUSP1 in both the SAT and PBMCs, with a parallel increase in the expression of PGC-1a and a reduction in the levels of p-JNK and p-ERK along with attenuated inflammatory response. Collectively, our data suggest that DUSP1 upregulation is strongly linked to adiposity and that physical exercise modulates its expression. This gives further evidence that exercise might be useful as a strategy for managing obesity and preventing its associated complications.

Original languageEnglish
Pages (from-to)E71-E83
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume308
Issue number1
DOIs
Publication statusPublished - 1 Jan 2015

Keywords

  • Dual-specificity phosphatase 1
  • Mitogen-activated protein kinase phosphatase 1
  • Obesity
  • Peroxisome proliferator-acti-vated receptor-γ coactivator-1α
  • Physical exercise

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