Map Kinase Phosphatase Dusp1 Is Overexpressed In Human Obese And Modulated By Physical Exercise

Abstract

Chronic low-grade inflammation and uncontrolled metabolic stress response are cardinal features of obesity; a major risk factor for the development diabetes. Dual specificity protein phosphatase 1 (DUSP1) 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 non-diabetic human subjects using subcutaneous adipose tissue and peripheral blood mononuclear cells. The levels of DUSP1 mRNA and protein were significantly increased in obese subjects with concomitant decrease in the phosphorylation of p38 MAPK and PGC-1α and an increase in the levels of phospho-JNK and phospho-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 VO2, Max and high-density lipoprotein (P<0.05). The observation that DUSP1 was overexpressed in obese subjects prompted us to investigate if physical exercise could reduce its expression. In this study, we report for the first time that physical exercise significantly attenuated the expression of DUSP1 with a parallel increase in the expression of PGC-1α and a reduction in JNK and ERK activities along with attenuated inflammatory response. Collectively, our data suggest that DUSP1 upregulation is strongly linked to adiposity and 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.