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

Medientyp: E-Artikel
Titel: 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 : Role of Glucagon-Like Peptide-1
Beteiligte: 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.
Erschienen: Ovid Technologies (Wolters Kluwer Health), 2015
Erschienen in: Circulation
Sprache: Englisch
DOI: 10.1161/circulationaha.114.011791
ISSN: 0009-7322; 1524-4539
Schlagwörter: Physiology (medical) ; Cardiology and Cardiovascular Medicine
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Beschreibung: <jats:sec> <jats:title>Background—</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods and Results—</jats:title> <jats:p> 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 exendin <jats:sub>9-39</jats:sub> (10 μg·kg <jats:sup>−1</jats:sup> ·h <jats:sup>−1</jats:sup> ). 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. </jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions—</jats:title> <jats:p>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.</jats:p> </jats:sec>
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