title: MAP kinase phosphatase DUSP1 is overexpressed in obese humans and modulated by physical exercise.
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 phosphorylation 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 V̇O(2max) 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-1α 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.
authors.affiliation: Deptartment of Biomedical Research.
authors.forename: Abdelkrim
authors.initials: A
authors.lastname: Khadir
authors.affiliation: Deptartment of Biomedical Research.
authors.forename: Ali
authors.initials: A
authors.lastname: Tiss
authors.affiliation: Deptartment of Biomedical Research.
authors.forename: Jehad
authors.initials: J
authors.lastname: Abubaker
authors.affiliation: Deptartment of Biomedical Research.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Abu-Farha
authors.affiliation: Deptartment of Biomedical Research.
authors.forename: Irina
authors.initials: I
authors.lastname: Al-Khairi
authors.affiliation: Deptartment of Biomedical Research.
authors.forename: Preethi
authors.initials: P
authors.lastname: Cherian
authors.affiliation: Deptartment of Biomedical Research.
authors.forename: Jeena
authors.initials: J
authors.lastname: John
authors.affiliation: Deptartment of Biomedical Research.
authors.forename: Sina
authors.initials: S
authors.lastname: Kavalakatt
authors.affiliation: Deptartment of Biomedical Research.
authors.forename: Samia
authors.initials: S
authors.lastname: Warsame
authors.affiliation: Deptartment of Biomedical Research.
authors.forename: Ashraf
authors.initials: A
authors.lastname: Al-Madhoun
authors.affiliation: Fitness and Rehabilitation Center, and.
authors.forename: Fahad
authors.initials: F
authors.lastname: Al-Ghimlas
authors.affiliation: Department of Biostatistics and Epidemiology, Dasman Diabetes Institute, Kuwait City, Kuwait;
authors.forename: Naser
authors.initials: N
authors.lastname: Elkum
authors.affiliation: Deptartment of Biomedical Research, Fitness and Rehabilitation Center, and Department of Biostatistics and Epidemiology, Dasman Diabetes Institute, Kuwait City, Kuwait;
authors.forename: Kazem
authors.initials: K
authors.lastname: Behbehani
authors.affiliation: King Fahad Specialist Hospital, Dammam, Saudi Arabia; and.
authors.forename: Said
authors.initials: S
authors.lastname: Dermime
authors.affiliation: Diabetes Research Centre, Qatar Biomedical Research Institute, Qatar Foundation, Doha, Qatar mdehbi@qf.org.qa.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Dehbi
mesh_terms: D050154:Adiposity / Q000235:genetics; D000328:Adult; D015331:Cohort Studies; D054638:Dual Specificity Phosphatase 1 / Q000235:genetics* / Q000378:metabolism; D015444:Exercise / Q000502:physiology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D013851:Thinness / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
chemical_list: C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1
keywords: dual-specificity phosphatase 1; mitogen-activated protein kinase phosphatase 1; obesity; peroxisome proliferator-activated receptor-γ coactivator-1α; physical exercise