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

Article

关键词: CARDIOVASCULAR RISK;    BARIATRIC SURGERY;    INSULIN-RESISTANCE;    HYPOCALORIC DIET;    OXIDATIVE STRESS;    GLP-1 ANALOG;    DYSFUNCTION;    RECEPTOR;    CELLS;    LIRAGLUTIDE;   

DOI  :  10.1161/CIRCULATIONAHA.114.011791

来源: SCIE

【 摘 要 】

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 (MTh) 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 shun-operated rats that were weight matched to those undergoing RYC1B. 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 CILP-1 receptor antagonist exendin9..39 (10 pg.kg-th-t). Furthermore, in patients and rats, RYCIB rapidly reversed 111X, 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 IMF-mediated cholesterol efflux capacity. To demonstrate the role of increased ClI,P-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 TIDE endothelium-protective properties, mimicking the effects of RYGB, Conclusions-RYC1B rapidly reverses obesity-induced endothelial dysfunction and restores the endothelium-protective properties of I IDE 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.

【 授权许可】

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