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Metabolic syndrome (MetS) represents a group of abnormalities that enhances the risk for cardiovascular disease, diabetes and stroke. The Mediterranean diet seems to be an important dietary pattern, which reduces the incidence of MetS. Hydroxytyrosol (HT) - a simple phenol found in olive oil - has received increased attention for its antioxidant activity. Recently, the European Foods Safety Authority (EFSA) claimed that dietary consumption of HT exhibits a protective role against cardiovascular disease. In this study, an experimental protocol has been setup, including isolated HT administration in a diet induced model of MetS in young Wistar rats, in order to find out whether HT has a protective effect against MetS. Rats were randomly divided into two groups nurtured by high-carbohydrate high-fat (H) (MetS inducing diet) and high-carbohydrate high-fat + HT (HHT). HT (20mg/kg/d oral gavage, water vehicle) was administered for 8 weeks on the basal diet. Previous pharmacological evaluation of HT showed that hepatic steatosis was reduced and the inflammatory cells into the liver were infiltrated. These indicate that HT shows bioactivity against metabolic syndrome. Therefore, the metabolomics evaluation of liver extracts would indicate the putative biochemical mechanisms of HT activity. Thus, the extracts of liver tissues were analyzed using Ultra Performance Liquid Chromatography - High Resolution Mass Spectrometry (UPLC-HRMS, Orbitrap Discovery) and Nuclear Magnetic Resonance (NMR) spectroscopy (Bruker Avance III 600MHz). Multivariate analysis was performed in order to gain insight on the metabolic effects of HT administration on the liver metabolome. Normalization employing multiple internal standards and Quality Control-based Robust LOESS (LOcally Estimated Scatterplot Smoothing) Signal Correction algorithm (QC-RLSC) was added in the processing pipeline to enhance the reliability of metabolomic analysis by reducing unwanted information. Experimentally, HHT rats were clearly distinguished from H in PLS-DA, showing differences in the liver metabolome between the groups and specific biomarkers were determined supporting the pharmacological findings. More specifically, HT has shown to be effective towards the mobilization of lipids as various lipid classes being differentially regulated between the H and HHT groups. Interestingly branched fatty acid esters of hydroxy oleic acids (OAHSA) lipids have been shown to be up regulated to the HHT group, denoting the alleviation of the MetS to the animals administered with HT., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Metabolic syndrome is a clustering of interrelated risk factors for cardiovascular disease and diabetes. The Mediterranean diet has been proposed as an important dietary pattern to confer cardioprotection by attenuating risk factors of metabolic syndrome. Hydroxytyrosol (HT) is present in olive fruit and oil, which are basic constituents of the Mediterranean diet. In this study, we have shown that treatment with HT (20mg/kg/d for 8 weeks) decreased adiposity, improved impaired glucose and insulin tolerance, improved endothelial function with lower systolic blood pressure, decreased left ventricular fibrosis and resultant diastolic stiffness and reduced markers of liver damage in a diet-induced rat model of metabolic syndrome. These results were accompanied by reduced infiltration of monocytes/macrophages into the heart with reduced biomarkers of oxidative stress. Furthermore, in an HRMS-based metabolism study of HT, we have identified 24 HT phase I and II metabolites, six of them being over-produced in high-starch, low-fat diet fed rats treated with HT compared to obese rats on high-carbohydrate, high-fat diet. These results provide direct evidence for cardioprotective effects of hydroxytyrosol by attenuation of metabolic risk factors. The implications of altered metabolism of HT in high-carbohydrate, high-fat diet fed obese rats warrant further investigation., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Black pepper is used worldwide to enhance food flavor. We investigated dietary supplementation with piperine, the active principle of black pepper, to high carbohydrate, high fat (HCHF) diet-fed rats as a model of human metabolic syndrome. Rats were fed with either HCHF diet (carbohydrate, 52%; fat, 24%; 25% fructose in drinking water) or cornstarch (CS) diet for a total of 16 weeks. Diets of the treatment groups (CS + piperine and HCHF + piperine) were supplemented with piperine for the last 8 weeks of this protocol. After 16 weeks, rats fed with HCHF diet developed hypertension, elevated oxidative stress and inflammation-induced cardiac changes (infiltration of inflammatory cells in heart, increase in count and degranulation of mast cells in heart, cardiac fibrosis and increase in ventricular stiffness), reduced responsiveness of aortic rings, impaired glucose tolerance, abdominal obesity together with liver fibrosis, fat deposition and increased plasma liver enzymes. Supplementation with piperine (375 mg/kg food; approximately 30 mg/kg/day) in HCHF-fed rats normalized blood pressure, improved glucose tolerance and reactivity of aortic rings, reduced plasma parameters of oxidative stress and inflammation, attenuated cardiac and hepatic inflammatory cell infiltration and fibrosis and improved liver function. These changes clearly suggest that piperine reduces symptoms of human metabolic syndrome in HCHF-fed rats by reducing inflammation and oxidative stress.

Tocotrienols have been reported to improve lipid profiles, reduce atherosclerotic lesions, decrease blood glucose and glycated haemoglobin concentrations, normalise blood pressure in vivo and inhibit adipogenesis in vitro, yet their role in the metabolic syndrome has not been investigated. In this study, we investigated the effects of palm tocotrienol-rich fraction (TRF) on high carbohydrate, high fat diet-induced metabolic, cardiovascular and liver dysfunction in rats. Rats fed a high carbohydrate, high fat diet for 16 weeks developed abdominal obesity, hypertension, impaired glucose and insulin tolerance with increased ventricular stiffness, lower systolic function and reduced liver function. TRF treatment improved ventricular function, attenuated cardiac stiffness and hypertension, and improved glucose and insulin tolerance, with reduced left ventricular collagen deposition and inflammatory cell infiltration. TRF improved liver structure and function with reduced plasma liver enzymes, inflammatory cell infiltration, fat vacuoles and balloon hepatocytes. TRF reduced plasma free fatty acid and triglyceride concentrations but only omental fat deposition was decreased in the abdomen. These results suggest that tocotrienols protect the heart and liver, and improve plasma glucose and lipid profiles with minimal changes in abdominal obesity in this model of human metabolic syndrome.

Age-related physiological changes develop at the same time as the increase in metabolic syndrome in humans after young adulthood. There is a paucity of data in models mimicking chronic diet-induced changes in human middle age and interventions to reverse these changes. This study measured the changes during chronic consumption of a high-carbohydrate (as cornstarch), low-fat (C) diet and a high-carbohydrate (as fructose and sucrose), high-fat (H) diet in rats for 32 wk. C diet feeding induced changes without metabolic syndrome, such as disproportionate increases in total body lean and fat mass, reduced bone mineral content, cardiovascular remodeling with increased systolic blood pressure, left ventricular and arterial stiffness, and increased plasma markers of liver injury. H diet feeding induced visceral adiposity with reduced lean mass, increased lipid infiltration in the skeletal muscle, impaired glucose and insulin tolerance, cardiovascular remodeling, hepatic steatosis, and increased infiltration of inflammatory cells in the heart and the liver. Chia seed supplementation for 24 wk attenuated most structural and functional modifications induced by age or H diet, including increased whole body lean mass and lipid redistribution from the abdominal area, and normalized the chronic low-grade inflammation induced by H diet feeding; these effects may be mediated by increased metabolism of anti-inflammatory n-3 fatty acids from chia seed. These results suggest that chronic H diet feeding for 32 wk mimics the diet-induced cardiovascular and metabolic changes in middle age and that chia seed may serve as an alternative dietary strategy in the management of these changes.

Chia seeds contain the essential fatty acid, α-linolenic acid (ALA). This study has assessed whether chia seeds attenuated the metabolic, cardiovascular and hepatic signs of a high-carbohydrate, high-fat (H) diet [carbohydrates, 52% (wt/wt); fat, 24% (wt/wt) with 25% (wt/vol) fructose in drinking water] in rats. Diets of the treatment groups were supplemented with 5% chia seeds after 8 weeks on H diet for a further 8 weeks. Compared with the H rats, chia seed-supplemented rats had improved insulin sensitivity and glucose tolerance, reduced visceral adiposity, decreased hepatic steatosis and reduced cardiac and hepatic inflammation and fibrosis without changes in plasma lipids or blood pressure. Chia seeds induced lipid redistribution with lipid trafficking away from the visceral fat and liver with an increased accumulation in the heart. The stearoyl-CoA desaturase-1 products were depleted in the heart, liver and the adipose tissue of chia seed-supplemented rats together with an increase in the substrate concentrations. The C18:1trans-7 was preferentially stored in the adipose tissue; the relatively inert C18:1n-9 was stored in sensitive organs such as liver and heart and C18:2n-6, the parent fatty acid of the n-6 pathway, was preferentially metabolized. Thus, chia seeds as a source of ALA induce lipid redistribution associated with cardioprotection and hepatoprotection., (Copyright © 2012 Elsevier Inc. All rights reserved.)