title: Impact of the prorenin/renin receptor on the development of obesity and associated cardiometabolic risk factors.
abstract: OBJECTIVE
  Obesity is a worldwide epidemic and current treatments have limited success thus, novel therapies are warranted. Our objective was to determine whether the prorenin/renin receptor [(P)RR] is implicated in obesity.
  
  
  METHODS
  Mice received a normal or high-fat/high-carbohydrate diet with the handle region peptide (HRP), a (P)RR blocker, or saline for 10 weeks. Post-menopausal non-diabetic obese women were enrolled in the Complication Associated with Obesity Study and were classified as insulin-resistant (IRO) or -sensitive (ISO) using a hyperinsulinemic-euglycemic clamp.
  
  
  RESULTS
  In mice, obesity increased the (P)RR by twofold in adipose tissue. Likewise, renin increased by at least twofold. The HRP reduced weight gain in obese mice by 20% associated to a 19% decrease in visceral fat. This was accompanied by a 48% decrease in leptin mRNA in fat and 33% decrease in circulating leptin. Inflammatory markers were also decreased by the HRP treatment. HRP normalized triglyceridemia and reduced insulinemia by 34% in obese mice. Interestingly, we observed a 33% increase in (P)RR mRNA in the fat of IRO women compared to ISO.
  
  
  CONCLUSIONS
  This is the first report of a potential implication in obesity of the (P)RR which may be a novel therapeutic target.
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM); Department of Biochemistry and Molecular Medicine of the Université de Montréal; Montreal Diabetes Research Center.
authors.forename: Paul
authors.initials: P
authors.lastname: Tan
authors.forename: Zulaykho
authors.initials: Z
authors.lastname: Shamansurova
authors.forename: Sandra
authors.initials: S
authors.lastname: Bisotto
authors.forename: Catherine
authors.initials: C
authors.lastname: Michel
authors.forename: Marie-Soleil
authors.initials: MS
authors.lastname: Gauthier
authors.forename: Rémi
authors.initials: R
authors.lastname: Rabasa-Lhoret
authors.forename: Thi M-D
authors.initials: TM
authors.lastname: Nguyen
authors.forename: Peter W
authors.initials: PW
authors.lastname: Schiller
authors.forename: Jolanta
authors.initials: J
authors.lastname: Gutkowska
authors.forename: Julie L
authors.initials: JL
authors.lastname: Lavoie
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D024821:Metabolic Syndrome / Q000209:etiology* / Q000235:genetics; D051379:Mice; D008820:Mice, Obese; D008822:Mice, Transgenic; D009765:Obesity / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D012083:Renin / Q000235:genetics / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000502:physiology; D012307:Risk Factors; D000093342:Prorenin Receptor
chemical_list: D011956:Receptors, Cell Surface; D012083:Renin; D000093342:Prorenin Receptor