title: Blocking the urotensin II receptor pathway ameliorates the metabolic syndrome and improves cardiac function in obese mice.
abstract: The metabolic syndrome is defined by the presence of hyperlipidemia, obesity, hypertension, and diabetes. The syndrome is associated with significant cardiovascular morbidity and mortality. The aim of the present study was to determine the role of the vasoactive peptide urotensin II (UII) in the pathogenesis of the metabolic syndrome. We used obese mice (ob/ob) to determine the effect of UII receptor (UT) blockage on the different facets of the metabolic syndrome with special emphasis on cardiac function. Our data demonstrate a significant increase in UII and UT expression in the myocardium of obese mice accompanied by a significant decrease in sarco/endoplasmic reticulum Ca(2+)-ATPase 2a (SERCA2a) expression, as well as intracellular Na(+) and Ca(2+) compared with wild-type mice (P<0.05). Treatment of ob/ob mice with the UII receptor antagonist SB657510 significantly improved glucose levels, blood pressure, hyperlipidemia, expression of myocardial SERCA2a, intracellular Na(+) and Ca(2+) and cardiac function in association with a decrease in weight gain, and mammalian target of rapamycin (mTOR) and sodium/hydrogen exchanger 1 (NHE-1) protein expression compared with vehicle (P<0.05). These findings demonstrate an important role for UII in the pathogenesis of the metabolic syndrome and suggest that the use of UT receptor antagonists may provide a new therapeutic tool for the treatment of this syndrome.
authors.affiliation: 1McGill University Health Center, Ste. C9-166, Montreal General Hospital, 1650 Cedar Ave., Montreal, Quebec H3G 1A4, Canada. adel.schwertani@mcgill.ca.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: You
authors.forename: Hamood
authors.initials: H
authors.lastname: Al Kindi
authors.forename: Ahmad
authors.initials: A
authors.lastname: Abdul-Karim
authors.forename: Piere-Olivier
authors.initials: PO
authors.lastname: Barrette
authors.forename: Adel
authors.initials: A
authors.lastname: Schwertani
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D006321:Heart / Q000503:physiopathology*; D024821:Metabolic Syndrome / Q000503:physiopathology*; D051379:Mice; D009765:Obesity / Q000503:physiopathology*; D016133:Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000378:metabolism*; D014579:Urotensins / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D011956:Receptors, Cell Surface; D014579:Urotensins; C029677:urotensin II
keywords: UT; heart; ob/ob