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SHR Neuro Cancer Cardio Lipid Metab Microb

Osto, E; Doytcheva, P; Corteville, C; Bueter, M; Dörig, C; Stivala, S; Buhmann, H; Colin, S; Rohrer, L; Hasballa, R; Tailleux, A; Wolfrum, C; Tona, F; Manz, J; Vetter, D; Spliethoff, K; Vanhoutte, PM; Landmesser, U; Pattou, F; Staels, B; Matter, CM; Lutz, TA; Lüscher, TF.
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.
Circulation. 2015; 131(10):871-81 Doi: 10.1161/CIRCULATIONAHA.114.011791
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Leading authors Med Uni Graz

Osto Elena

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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.

Find related publications in this database (using NLM MeSH Indexing)

Adult - administration & dosage

Animals - administration & dosage

Antioxidants - physiology

Body Weight - physiology

Case-Control Studies - administration & dosage

Cells, Cultured - administration & dosage

Diet, High-Fat - adverse effects

Disease Models, Animal - administration & dosage

Endothelium, Vascular - pathology, physiology

Female - administration & dosage

Gastric Bypass - administration & dosage

Glucagon-Like Peptide 1 - physiology

Humans - administration & dosage

Lipoproteins, HDL - physiology

Male - administration & dosage

Nitric Oxide - physiology

Obesity - physiopathology, surgery

Oxidative Stress - physiology

Proto-Oncogene Proteins c-akt - physiology

Rats - administration & dosage

Rats, Wistar - administration & dosage

Signal Transduction - administration & dosage

Treatment Outcome - administration & dosage

Weight Loss - physiology

Find related publications in this database (Keywords)

bariatric surgery

endothelium

glucagon-like peptide-1

lipoproteins

nitric oxide

obesity

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