Grape pomace extract induced beige cells in white adipose tissue from rats and in 3T3-L1 adipocytes.

This study investigated the effects of a grape pomace extract (GPE) rich in phenolic compounds on brown-like adipocyte induction and adiposity in spontaneously hypertensive (SHR) and control normotensive Wistar-Kyoto (WKY) rats fed a high-fat diet (HFD). HFD consumption for 10 weeks significantly increased epididymal white adipose tissue (eWAT) in WKY but not in SHR rats. Supplementation with GPE (300 mg/kg body weight/day) reduced adipocyte diameter and increased levels of proteins that participate in adipogenesis and angiogenesis, i.e., peroxisome-proliferator activated receptor gamma (PPARγ), vascular endothelial grow factor-A (VEGF-A) and its receptor 2 (VEGF-R2), and partially increased the uncoupling protein 1 (UCP-1) in WKY. In both strains, GPE attenuated adipose inflammation. In eWAT from SHR, GPE increased the expression of proteins involved in adipose tissue "browning," i.e., PPARγ-coactivator-1α (PGC-1α), PPARγ, PR domain containing 16 (PRDM16) and UCP-1. In primary cultures of SHR adipocytes, GPE-induced UCP-1 up-regulation was dependent on p38 and ERK activation. Accordingly, in 3T3-L1 adipocytes treated with palmitate, the addition of GPE (30 µM) activated the ß-adrenergic signaling cascade (PKA, AMPK, p38, ERK). This led to the associated up-regulation of proteins involved in mitochondrial biogenesis (PGC-1α, PPARγ, PRDM16 and UCP-1) and fatty acid oxidation (ATGL). These effects were similar to those exerted by (-)-epicatechin and quercetin, major phenolic compounds in GPE. Overall, in HFD-fed rats, supplementation with GPE promoted brown-like cell formation in eWAT and diminished adipose dysfunction. Thus, winemaking residues, rich in bioactive compounds, could be useful to mitigate the adverse effects of HFD-induced adipose dysfunction.

Grape pomace and grape pomace extract improve insulin signaling in high-fat-fructose fed rat-induced metabolic syndrome.

In this study the effect of diet supplementation with grape pomace (GP) and grape pomace extract (GPE) on insulin sensitive tissues (adipose, liver and muscle) was evaluated in an experimental model of metabolic syndrome (MetS). MetS was developed by giving a high-fat-fructose (HFF) diet to Wistar rats. Six weeks of HFF diet induced weight gain, which was partially attenuated by GP (1 g per kg per day) and GPE (300 mg per kg per day) supplementation. HFF diet increased systolic blood pressure, triglycerides, insulin resistance (HOMA:IR) and inflammation (c-reactive protein (CRP)). Supplementation with GP prevented SBP, triglycerides and CRP increased and partially attenuated insulin resistance. On the other hand, GPE partially reduced SBP and triglycerides and significantly prevented insulin resistance and inflammation. Also, HFF diet induced higher triglycerides content and enhanced NADPH oxidase activity in the liver. Also, HFF diet increased the epididymal adipose tissue weight, enlarged adipocyte size, and c-jun N-terminal kinase (JNK) activation, probably contributing to a pro-inflammatory cytokine pattern (higher resistin) and lower adiponectin protein expression. These alterations may result in an impairment of insulin signaling cascade observed in adipose, liver and muscle tissue (IRS1, Akt, and extracellular signal-regulated kinases (ERK1/2)) from HFF rats. Supplementation with GP and to a greater extent GPE attenuated liver triglyceride content and adiposity and restored adipose, liver and muscle response to insulin. These findings show that supplementation with GP and GPE to a greater extent can counteract adiposity, inflammation, liver damage and impaired insulin signaling associated to MetS, supporting the utilization of winemaking residues in food industry/human health due to their high amount of bioactive compounds.

Garlic and onion attenuates vascular inflammation and oxidative stress in fructose-fed rats.

This study evaluates the antioxidant and the anti-inflammatory properties of garlic (G) and onion (O) in fructose-fed rats (FFR). Thirty-day-old male Wistar rats were assigned to control (C), F (10% fructose in drinking water), F+T (tempol 1 mM as control antioxidant), F+G, and F+O. Aqueous G and O extracts were administered orally in doses of 150 and 400 mg/kg/d respectively, and along with tempol, were given during the last 8 weeks of a 14-week period. At the end of the study, FFR had developed insulin resistance, aortic NADPH oxidase activity, increased SBP, plasma TBARS and vascular cell adhesion molecule-1 (VCAM-1) expression in mesenteric arteries, and a decrease in heart endothelial nitric oxide synthase (eNOS). Garlic and onion administration to F rats reduced oxidative stress, increased eNOS activity, and also attenuated VCAM-1 expression. These results provide new evidence showing the anti-inflammatory and antioxidant effect of these vegetables.

Aqueous garlic extracts prevent oxidative stress and vascular remodeling in an experimental model of metabolic syndrome.

The organosulfur profile and the effect on oxidative stress and vascular remodeling in fructose-fed rats (FFR) were evaluated in Fuego INTA and Morado INTA garlic cultivars. Wistar rats were fed either normal rat chow (control) or the same diet plus 10% fructose in drinking water. During the last 6 weeks of a 12 week period of the corresponding diet, a subgroup of control and FFR received an aqueous extract of Fuego INTA and Morado INTA. Fuego INTA showed higher levels of total thiosulfinates, allicin, and pungency than Morado INTA. FFR showed an increase of systolic blood pressure, aortic NAD(P)H oxidase activity, plasma thiobarbituric acid reactive substances, and vascular remodeling that was significantly reduced after both garlic administrations. The beneficial effect was slightly higher when Fuego INTA was administered. Both aqueous garlic extracts prevent oxidative stress and vascular remodeling in rats with metabolic syndrome, suggesting the existence of slight differences among cultivars.

Dealcoholized red wine reverse vascular remodeling in an experimental model of metabolic syndrome: role of NAD(P)H oxidase and eNOS activity.

The present study examines the effect of chronic administration of dealcoholized red wine Malbec (DRW) on vascular remodeling and NAD(P)H oxidase and endothelial nitric oxide synthase activity (eNOS) in an experimental model of metabolic syndrome induced by fructose administration. Thirty-day old male Wistar rats were fed a normal rat diet (control) or the same diet plus 10% fructose in drinking water (FFR). During the last 4 weeks of a 10-week period of the corresponding diet, a subgroup of control and FFR (n=8 each) received DRW in their drinking water. Systolic blood pressure (SBP), a homeostasis model assessment of insulin resistance (HOMA-IR), aortic NAD(P)H oxidase and eNOS activity in the heart and vascular tissue were evaluated. Vascular remodeling was evaluated in the left carotid artery (CA) and interlobar, arcuate and interlobular renal arteries (RA) through lumen to media (L/M) ratio determination. At the end of the study FFR increased the SBP (p < 0.001), HOMA-IR (p < 0.001), and aortic NAD(P)H oxidase activity (p < 0,05) but reduced cardiac and vascular eNOS activity (p < 0.01), L/M ratio in CA (p < 0.001) and RA (p < 0.01) compared with the C group. DRW reduced SBP (p < 0.05), aortic NAD(P)H oxidase (p < 0.05), and recovered eNOS activity (p < 0.001) and L/M in CA (p < 0.001) and RA (p < 0.001) compared with FFR. This study provides new data about the beneficial effect of DRW on oxidative stress and vascular remodeling in the experimental model of metabolic syndrome. Data suggest the participation of mechanisms involving oxidative stress in FFR alterations and the usefulness of natural antioxidant substances present in red wine in the reversion of these changes.