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Rapid and body weight-independent improvement of endothelial and high-density lipoprotein function after Roux-en-Y gastric bypass: role of glucagon-like peptide-1.
Osto, Elena; Doytcheva, Petia; Corteville, Caroline; Bueter, Marco; Dörig, Claudia; Stivala, Simona; Buhmann, Helena; Colin, Sophie; Rohrer, Lucia; Hasballa, Reda; Tailleux, Anne; Wolfrum, Christian; Tona, Francesco; Manz, Jasmin; Vetter, Diana; Spliethoff, Kerstin; Vanhoutte, Paul M; Landmesser, Ulf; Pattou, Francois; Staels, Bart; Matter, Christian M; Lutz, Thomas A; Lüscher, Thomas F.
Afiliação
  • Osto E; From Centre for Molecular Cardiology, University of Zurich and University Heart Center, Cardiology, University Hospital Zurich, Switzerland (E.O., P.D., S.S., J.M., U.L., C.M.M., T.F.L.); Institute of Veterinary Physiology, University of Zurich, Switzerland (P.D., C.C., C.D., H.B., K.S., T.A.L.); De
  • Doytcheva P; From Centre for Molecular Cardiology, University of Zurich and University Heart Center, Cardiology, University Hospital Zurich, Switzerland (E.O., P.D., S.S., J.M., U.L., C.M.M., T.F.L.); Institute of Veterinary Physiology, University of Zurich, Switzerland (P.D., C.C., C.D., H.B., K.S., T.A.L.); De
  • Corteville C; From Centre for Molecular Cardiology, University of Zurich and University Heart Center, Cardiology, University Hospital Zurich, Switzerland (E.O., P.D., S.S., J.M., U.L., C.M.M., T.F.L.); Institute of Veterinary Physiology, University of Zurich, Switzerland (P.D., C.C., C.D., H.B., K.S., T.A.L.); De
  • Bueter M; From Centre for Molecular Cardiology, University of Zurich and University Heart Center, Cardiology, University Hospital Zurich, Switzerland (E.O., P.D., S.S., J.M., U.L., C.M.M., T.F.L.); Institute of Veterinary Physiology, University of Zurich, Switzerland (P.D., C.C., C.D., H.B., K.S., T.A.L.); De
  • Dörig C; From Centre for Molecular Cardiology, University of Zurich and University Heart Center, Cardiology, University Hospital Zurich, Switzerland (E.O., P.D., S.S., J.M., U.L., C.M.M., T.F.L.); Institute of Veterinary Physiology, University of Zurich, Switzerland (P.D., C.C., C.D., H.B., K.S., T.A.L.); De
  • Stivala S; From Centre for Molecular Cardiology, University of Zurich and University Heart Center, Cardiology, University Hospital Zurich, Switzerland (E.O., P.D., S.S., J.M., U.L., C.M.M., T.F.L.); Institute of Veterinary Physiology, University of Zurich, Switzerland (P.D., C.C., C.D., H.B., K.S., T.A.L.); De
  • Buhmann H; From Centre for Molecular Cardiology, University of Zurich and University Heart Center, Cardiology, University Hospital Zurich, Switzerland (E.O., P.D., S.S., J.M., U.L., C.M.M., T.F.L.); Institute of Veterinary Physiology, University of Zurich, Switzerland (P.D., C.C., C.D., H.B., K.S., T.A.L.); De
  • Colin S; From Centre for Molecular Cardiology, University of Zurich and University Heart Center, Cardiology, University Hospital Zurich, Switzerland (E.O., P.D., S.S., J.M., U.L., C.M.M., T.F.L.); Institute of Veterinary Physiology, University of Zurich, Switzerland (P.D., C.C., C.D., H.B., K.S., T.A.L.); De
  • Rohrer L; From Centre for Molecular Cardiology, University of Zurich and University Heart Center, Cardiology, University Hospital Zurich, Switzerland (E.O., P.D., S.S., J.M., U.L., C.M.M., T.F.L.); Institute of Veterinary Physiology, University of Zurich, Switzerland (P.D., C.C., C.D., H.B., K.S., T.A.L.); De
  • Hasballa R; From Centre for Molecular Cardiology, University of Zurich and University Heart Center, Cardiology, University Hospital Zurich, Switzerland (E.O., P.D., S.S., J.M., U.L., C.M.M., T.F.L.); Institute of Veterinary Physiology, University of Zurich, Switzerland (P.D., C.C., C.D., H.B., K.S., T.A.L.); De
  • Tailleux A; From Centre for Molecular Cardiology, University of Zurich and University Heart Center, Cardiology, University Hospital Zurich, Switzerland (E.O., P.D., S.S., J.M., U.L., C.M.M., T.F.L.); Institute of Veterinary Physiology, University of Zurich, Switzerland (P.D., C.C., C.D., H.B., K.S., T.A.L.); De
  • Wolfrum C; From Centre for Molecular Cardiology, University of Zurich and University Heart Center, Cardiology, University Hospital Zurich, Switzerland (E.O., P.D., S.S., J.M., U.L., C.M.M., T.F.L.); Institute of Veterinary Physiology, University of Zurich, Switzerland (P.D., C.C., C.D., H.B., K.S., T.A.L.); De
  • Tona F; From Centre for Molecular Cardiology, University of Zurich and University Heart Center, Cardiology, University Hospital Zurich, Switzerland (E.O., P.D., S.S., J.M., U.L., C.M.M., T.F.L.); Institute of Veterinary Physiology, University of Zurich, Switzerland (P.D., C.C., C.D., H.B., K.S., T.A.L.); De
  • Manz J; From Centre for Molecular Cardiology, University of Zurich and University Heart Center, Cardiology, University Hospital Zurich, Switzerland (E.O., P.D., S.S., J.M., U.L., C.M.M., T.F.L.); Institute of Veterinary Physiology, University of Zurich, Switzerland (P.D., C.C., C.D., H.B., K.S., T.A.L.); De
  • Vetter D; From Centre for Molecular Cardiology, University of Zurich and University Heart Center, Cardiology, University Hospital Zurich, Switzerland (E.O., P.D., S.S., J.M., U.L., C.M.M., T.F.L.); Institute of Veterinary Physiology, University of Zurich, Switzerland (P.D., C.C., C.D., H.B., K.S., T.A.L.); De
  • Spliethoff K; From Centre for Molecular Cardiology, University of Zurich and University Heart Center, Cardiology, University Hospital Zurich, Switzerland (E.O., P.D., S.S., J.M., U.L., C.M.M., T.F.L.); Institute of Veterinary Physiology, University of Zurich, Switzerland (P.D., C.C., C.D., H.B., K.S., T.A.L.); De
  • Vanhoutte PM; From Centre for Molecular Cardiology, University of Zurich and University Heart Center, Cardiology, University Hospital Zurich, Switzerland (E.O., P.D., S.S., J.M., U.L., C.M.M., T.F.L.); Institute of Veterinary Physiology, University of Zurich, Switzerland (P.D., C.C., C.D., H.B., K.S., T.A.L.); De
  • Landmesser U; From Centre for Molecular Cardiology, University of Zurich and University Heart Center, Cardiology, University Hospital Zurich, Switzerland (E.O., P.D., S.S., J.M., U.L., C.M.M., T.F.L.); Institute of Veterinary Physiology, University of Zurich, Switzerland (P.D., C.C., C.D., H.B., K.S., T.A.L.); De
  • Pattou F; From Centre for Molecular Cardiology, University of Zurich and University Heart Center, Cardiology, University Hospital Zurich, Switzerland (E.O., P.D., S.S., J.M., U.L., C.M.M., T.F.L.); Institute of Veterinary Physiology, University of Zurich, Switzerland (P.D., C.C., C.D., H.B., K.S., T.A.L.); De
  • Staels B; From Centre for Molecular Cardiology, University of Zurich and University Heart Center, Cardiology, University Hospital Zurich, Switzerland (E.O., P.D., S.S., J.M., U.L., C.M.M., T.F.L.); Institute of Veterinary Physiology, University of Zurich, Switzerland (P.D., C.C., C.D., H.B., K.S., T.A.L.); De
  • Matter CM; From Centre for Molecular Cardiology, University of Zurich and University Heart Center, Cardiology, University Hospital Zurich, Switzerland (E.O., P.D., S.S., J.M., U.L., C.M.M., T.F.L.); Institute of Veterinary Physiology, University of Zurich, Switzerland (P.D., C.C., C.D., H.B., K.S., T.A.L.); De
  • Lutz TA; From Centre for Molecular Cardiology, University of Zurich and University Heart Center, Cardiology, University Hospital Zurich, Switzerland (E.O., P.D., S.S., J.M., U.L., C.M.M., T.F.L.); Institute of Veterinary Physiology, University of Zurich, Switzerland (P.D., C.C., C.D., H.B., K.S., T.A.L.); De
  • Lüscher TF; From Centre for Molecular Cardiology, University of Zurich and University Heart Center, Cardiology, University Hospital Zurich, Switzerland (E.O., P.D., S.S., J.M., U.L., C.M.M., T.F.L.); Institute of Veterinary Physiology, University of Zurich, Switzerland (P.D., C.C., C.D., H.B., K.S., T.A.L.); De
Circulation ; 131(10): 871-81, 2015 Mar 10.
Article em En | MEDLINE | ID: mdl-25673670
ABSTRACT

BACKGROUND:

Roux-en-Y gastric bypass (RYGB) reduces body weight and cardiovascular mortality in morbidly obese patients. Glucagon-like peptide-1 (GLP-1) seems to mediate the metabolic benefits of RYGB partly in a weight loss-independent manner. The present study investigated in rats and patients whether obesity-induced endothelial and high-density lipoprotein (HDL) dysfunction is rapidly improved after RYGB via a GLP-1-dependent mechanism. METHODS AND

RESULTS:

Eight days after RYGB in diet-induced obese rats, higher plasma levels of bile acids and GLP-1 were associated with improved endothelium-dependent relaxation compared with sham-operated controls fed ad libitum and sham-operated rats that were weight matched to those undergoing RYGB. Compared with the sham-operated rats, RYGB improved nitric oxide (NO) bioavailability resulting from higher endothelial Akt/NO synthase activation, reduced c-Jun amino terminal kinase phosphorylation, and decreased oxidative stress. The protective effects of RYGB were prevented by the GLP-1 receptor antagonist exendin9-39 (10 µg·kg(-1)·h(-1)). Furthermore, in patients and rats, RYGB rapidly reversed HDL dysfunction and restored the endothelium-protective properties of the lipoprotein, including endothelial NO synthase activation, NO production, and anti-inflammatory, antiapoptotic, and antioxidant effects. Finally, RYGB restored HDL-mediated cholesterol efflux capacity. To demonstrate the role of increased GLP-1 signaling, sham-operated control rats were treated for 8 days with the GLP-1 analog liraglutide (0.2 mg/kg twice daily), which restored NO bioavailability and improved endothelium-dependent relaxations and HDL endothelium-protective properties, mimicking the effects of RYGB.

CONCLUSIONS:

RYGB rapidly reverses obesity-induced endothelial dysfunction and restores the endothelium-protective properties of HDL via a GLP-1-mediated mechanism. The present translational findings in rats and patients unmask novel, weight-independent mechanisms of cardiovascular protection in morbid obesity.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Peso Corporal / Endotélio Vascular / Redução de Peso / Peptídeo 1 Semelhante ao Glucagon / Lipoproteínas HDL / Obesidade Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Animals / Female / Humans / Male Idioma: En Revista: Circulation Ano de publicação: 2015 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Peso Corporal / Endotélio Vascular / Redução de Peso / Peptídeo 1 Semelhante ao Glucagon / Lipoproteínas HDL / Obesidade Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Animals / Female / Humans / Male Idioma: En Revista: Circulation Ano de publicação: 2015 Tipo de documento: Article