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.

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.

3D simulation of the aqueous flow in the human eye.

Glaucoma results in an increase in the resistance of the aqueous humor outflow, which in turn leads to an increase of the intraocular pressure (IOP). Several treatments are proposed to reduce and stabilize the IOP that include medications, filtering surgery and glaucoma drainage devices (GDD). So far computational fluid dynamics (CFD) modeling of the eye drainage system has not yet been well studied. Therefore our goal was to provide a 3D CFD model of the eye based on the anatomy of a real human eye. Such a tool would serve for future evaluation of new glaucoma surgical techniques involving, for example, GDD. The model was based on stacks of microphotographs from human eye slides from which digital processing of the images of the eye structure and 3D reconstruction of the model were performed. Simulations of the distribution of pressure and flow velocity in the model of a healthy eye gave results comparable to physiology references. Mimicking glaucoma conditions led to an increase of the IOP from normal range, which went down to lower values after a filtering procedure. Further refinements in the boundary conditions for the filtering procedure shall improve the accuracy of this innovative tool for modeling glaucoma surgery.