Verónica Irribarra

A high-fat diet induces and red wine counteracts endothelial dysfunction in human volunteers

Endothelial dysfunction is associated with atherogenesis and oxidative stress in humans. In rat and rabbit blood vessels, wine polyphenol antioxidants induce vascular relaxationin vitro through the NO-cGMP pathway. To assess the effect of a regular high-fat diet (HFD) and moderate red wine consumption on endothelial function (EF), a study was performed in healthy male volunteers. EF was measured as flow-mediated dilatation of the brachial artery, employing high-resolution ultrasound after an overnight fast. Other clinical and biochemical parameters related to EF were also measured. Six volunteers received a control diet, rich in fruits and vegetables (27% calories as fat) and five volunteers received an HFD (39.5% calories as fat). Measurements were done twice on each volunteer: after a period of 30 d with diet plus 240 mL of red wine/d, and after a period of 30 d with diet, without wine. In the absence of wine, there is a reduction of EF with HFD when compared to the control diet (P=0.014). This loss of EF is not seen when both diets are supplemented with wine for 30 d (P=0.001). Plasma levels ofn−3 fatty acids (R2=0.232,P=0.023) and lycopene (R2=0.223,P=0.020) show a positive correlation with individual EF measurements, but they do not account for the significant differences observed among dietary groups or after wine supplementation. These results help elucidate the deleterious effect of a high-fat diet and the protective role of wine, n−3 fatty acids and dietary antioxidants in cardiovascular disease.

Medical and Surgical Treatments for Obesity Have Opposite Effects on Peptide YY and Appetite: A Prospective Study Controlled for Weight Loss

CONTEXT The effects of medical and surgical treatments for obesity on peptide YY (PYY) levels, in patients with similar weight loss, remain unclear. OBJECTIVE The objective of the study was to assess PYY and appetite before and after Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), and medical treatment (MED). DESIGN This was a prospective, controlled, nonrandomized study. SETTING The study was conducted at the Departments of Nutrition and Digestive Surgery at a university hospital. PARTICIPANTS PARTICIPANTS included three groups of eight patients with similar body mass indexes (RYGB 37.8 +/- 0.8, SG 35.3 +/- 0.7, and MED 39.1 +/- 1.7 kg/m(2), P = NS) and eight lean controls (body mass index 21.7 +/- 0.7 kg/m(2)). MAIN OUTCOME MEASURES Total plasma PYY, hunger, and satiety visual analog scales in fasting and after ingestion of a standard test meal were measured. RESULTS At baseline there were no differences in the area under the curve (AUC) of PYY, hunger, or satiety in obese groups. Two months after the interventions, RYGB, SG, and MED groups achieved similar weight loss (17.7 +/- 3, 14.9 +/- 2.4, 16.6 +/- 4%, respectively, P = NS). PYY AUC increased in RYGB (P < 0.001) and SG (P < 0.05) and did not change in MED. PYY levels decreased at fasting, 30 min, and 180 min after a standard test meal in MED (P < 0.05). Hunger AUC decreased in RYGB (P < 0.05). Satiety AUC increased in RYGB (P < 0.05) and SG (P < 0.05). Appetite did not change in MED. PYY AUC correlated with satiety AUC (r = 0.35, P < 0.05). CONCLUSION RYGB and SG increased PYY and reduced appetite. MED failed to produce changes. Different effects occur despite similar weight loss. This suggests that the weight-loss effects of these procedures are enhanced by an increase in PYY and satiety.

Bile acids synthesis decreases after laparoscopic sleeve gastrectomy

BACKGROUND Bariatric surgery is the most effective treatment alternative in morbid obesity. The mechanisms contributing to these benefits remain poorly understood. Bile acids (BAs) are mediators of different regulatory functions in glucose and cholesterol homeostasis and energy expenditure. Recent evidence suggests that BAs are critically important for the beneficial effects of sleeve gastrectomy (SG). OBJECTIVES The aim of this study was to evaluate the effect of SG on BA synthesis. SETTING University Hospital. Santiago, Chile. METHODS Obese patients were evaluated before and after SG (1, 3, 6, and 12 months). BA synthesis was evaluated through the serum marker, 7 α-hydroxy-4-cholesten-3-one (C4). Primary and secondary BA and C4 were determined by high performance liquid chromatography coupled with tandem mass spectrometry detection (HPLC-MS/MS). RESULTS From June 2013 to January 2014, 19 patients (age 37.6±7.8 years; BMI 35.8±3.5 kg/m(2); 79% female) were included in this study. Mean weight loss at 1, 3, 6, and 12 months was 11.3, 17.5, 23.6, and 25.4 kg, respectively, equivalent to 11.8, 18.6, 24.8, and 26.9 of total body water percentage (%TBW) (P<.0001), respectively and 43.2, 68.2, 91, and 98.8 of percentage of excess weight loss (%EWL), respectively (P<.001). Serum C4 levels at baseline, 1, 3, 6, and 12 months were 23.4±21.1, 4.9±8.2, 8.7±12.1, 13.8±12.9, and 18.8±16.8 ng/mL (P<.0001), respectively. Fibroblast growth factor 19 (FGF19) levels at baseline, 1, 3, 6, and 12 months were 71±33.3, 130.5±66.2, 117.8±57.2, 134.6±91.7, and 124.3±85.9 pg/mL (P = .019), respectively. CONCLUSION Serum levels of C4 decrease after SG, indicating a reduction in the synthesis of BA. FGF19 may play a role in decreasing BA synthesis. Further studies are necessary to characterize the effect of bariatric surgery on BA homeostasis.

Fisiopatología de la retinopatía y nefropatía diabéticas

Despite the availability of multiple therapeutic approaches, diabetes mellitus with chronic hyperglycemia remains as the main cause of new cases of blindness and chronic renal failure in the western hemisphere. We herein review the molecular mechanisms by which chronic hyperglycemia causes retinopathy and nephropathy in type I and type 2 diabetic patients. Diabetic retinopathy develops silently along years or decades, producing symptoms only in its very late stages. Its slow development starts with the activation of aldose reductase, shortly followed by the destruction of the retinal pericyte cells, and ends in sudden blindness when vitreous hemorrhage ensues. Nephropathy, on the other hand, centers its pathophysiology in the mesangial cell, that starts as a modified smooth-muscle cell, and turns itself into a myo-fibroblast, produces such amounts of cytoplasm and extracellular protein that strangulates the glomerular capillaries and causes renal failure. After a detailed review of the molecular mechanisms of the aforementioned complications, we conclude that, apart from directing our attention to the emerging medications that are being developed to block these molecular pathways, we should never abandon the struggle for improving the glycemic control of our diabetic patients.

589 Duodenojejunal Bypass Liner Increases Fasting and Postprandial Serum Levels of Bile Acids in Patients With Severe Obesity

information on anti-inflammatory or metabolic role of GPR120 at the level of intestinal epithelium is very limited. Further, GPR120 has been shown to be expressed in the intestine, however, its levels along the length of the intestine in various species have not been studied in detail. Aims: Our current studies, therefore, assessed the expression of GPR120 along the length of human, mouse and rat intestine. Further, we examined the anti-inflammatory effects and/or altered levels of the key aneroxigenic gut hormone glucagon-like peptide 1 (GLP1) in (i) model human intestinal epithelial Caco-2 and (ii) model mouse intestinal epithelial endocrine cell line STC-1 following GPR120 activation by synthetic (GW9508) or natural (ω-3 FA) agonists. Results: Both GPR120 mRNA and protein levels varied along the length of mouse and rat intestine in the order of proximal colon>cecum>distal colon>ileum>jejunum. Mucosal scrapings of different regions of organ donor human intestine also showed highest GPR120 protein level in the proximal colon. Cell-surface biotinylation and co-immunoprecipitation in Caco-2 cells, respectively, showed that GPR120 was internalized and bound to β-arrestin-2, a downstream signaling component of NF-κB activation, in response to 30 min exposure to GW9508 (50 μM) or eicosapentaenoic acid (EPA) (100 μM). These treatments also inhibited NF-κB reporter activity presumably via GPR120 binding to and sequestration of β-arrestin-2, inhibiting downstream signaling events. On the other hand, treatment of STC-1 cells with EPA or 10-trans,12-cis conjugated linoleic acid (100 μM, 6 hr) induced GLP1 intensity, as measured by immunofluorescence. However, in STC1 cells, GW9508/EPA treatments did not induce receptor internalization or sequestration of β-arrestin-2. Conclusion: Our studies for the first time demonstrate that agonist-stimulation of GPR120 in different cell types of the intestinal epithelium induces distinct signaling pathways to exert anti-inflammatory effects and modulate enteroendocrine function. Therefore, GPR120 appears to regulate diverse physiological processes at the level of intestinal epithelium to impact inflammatory and/or metabolic disorders. (Supported by NIH-NIDDK/ Bill & Melinda Gates Foundation).