Giuseppina Costabile

Differential alterations of the concentrations of endocannabinoids and related lipids in the subcutaneous adipose tissue of obese diabetic patients.

BackgroundThe endocannabinoids, anandamide and 2-AG, are produced by adipocytes, where they stimulate lipogenesis via cannabinoid CB1 receptors and are under the negative control of leptin and insulin. Endocannabinoid levels are elevated in the blood of obese individuals and nonobese type 2 diabetes patients. To date, no study has evaluated endocannabinoid levels in subcutaneous adipose tissue (SAT) of subjects with both obesity and type 2 diabetes (OBT2D), characterised by similar adiposity and whole body insulin resistance and lower plasma leptin levels as compared to non-diabetic obese subjects (OB).Design and MethodsThe levels of anandamide and 2-AG, and of the anandamide-related PPARα ligands, oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), in the SAT obtained by abdominal needle biopsy in 10 OBT2D, 11 OB, and 8 non-diabetic normal-weight (NW) subjects, were measured by liquid chromatography-mass spectrometry. All subjects underwent a hyperinsulinaemic euglycaemic clamp.ResultsAs compared to NW, anandamide, OEA and PEA levels in the SAT were 2-4.4-fold elevated (p < 0.05), and 2-AG levels 2.3-fold reduced (p < .05), in OBT2D but not in OB subjects. Anandamide, OEA and PEA correlated positively (p < .05) with SAT leptin mRNA and free fatty acid during hyperinsulinaemic clamp, and negatively with SAT LPL activity and plasma HDL-cholesterol, which were all specifically altered in OBT2D subjects.ConclusionsThe observed alterations emphasize, for the first time in humans, the potential different role and regulation of adipose tissue anandamide (and its congeners) and 2-AG in obesity and type 2 diabetes.

A whole-grain cereal-based diet lowers postprandial plasma insulin and triglyceride levels in individuals with metabolic syndrome.

BACKGROUND AND AIM Until recently, very few intervention studies have investigated the effects of whole-grain cereals on postprandial glucose, insulin and lipid metabolism, and the existing studies have provided mixed results. The objective of this study was to evaluate the effects of a 12-week intervention with either a whole-grain-based or a refined cereal-based diet on postprandial glucose, insulin and lipid metabolism in individuals with metabolic syndrome. METHODS AND RESULTS Sixty-one men and women age range 40-65 years, with the metabolic syndrome were recruited to participate in this study using a parallel group design. After a 4-week run-in period, participants were randomly assigned to a 12-week diet based on whole-grain products (whole-grain group) or refined cereal products (control group). Blood samples were taken at the beginning and end of the intervention, both fasting and 3 h after a lunch, to measure biochemical parameters. Generalized linear model (GLM) was used for between-group comparisons. Overall, 26 participants in the control group and 28 in the whole-grain group completed the dietary intervention. Drop-outs (five in the control and two in the whole-grain group) did not affect randomization. After 12 weeks, postprandial insulin and triglyceride responses (evaluated as average change 2 and 3 h after the meal, respectively) decreased by 29% and 43%, respectively, in the whole-grain group compared to the run-in period. Postprandial insulin and triglyceride responses were significantly lower at the end of the intervention in the whole-grain group compared to the control group (p = 0.04 and p = 0.05; respectively) whereas there was no change in postprandial response of glucose and other parameters evaluated. CONCLUSIONS A twelve week whole-grain cereal-based diet, compared to refined cereals, reduced postprandial insulin and triglycerides responses. This finding may have implications for type 2 diabetes risk and cardiovascular disease.

Effects of rye and whole wheat versus refined cereal foods on metabolic risk factors: A randomised controlled two-centre intervention study

BACKGROUND & AIMS Intervention studies investigating the effects of wholegrain intake on glucose and insulin metabolism have provided conflicting results. Aim of this study was the evaluation of glucose and insulin metabolism in response to long-term consumption of rye and whole wheat compared with a diet containing the same amount of refined cereal foods, in individuals with metabolic syndrome from two European locations (Kuopio-Finland/Naples-Italy). METHODS 146 individuals of both genders, age range 40-65 years with metabolic syndrome, were recruited to this study with parallel groups. After a 2-4 week run-in period, participants were assigned to a diet based on wholegrain (wholegrain group) or on refined cereal products (control group), each one for a duration of 12 weeks. Peripheral insulin sensitivity, assessed by FSIGT, lipids and inflammatory markers were measured before and at the end of intervention. RESULTS 61 participants in the control group and 62 in the wholegrain group completed the dietary intervention. Compliance to the two diets was good. At the end of the intervention, insulin sensitivity indices and secretion (SI, QUICKI, DI, dAIRG) and lipids and inflammatory markers did not change significantly in the wholegrain and control groups as compared with baseline and no differences between the two groups were observed. CONCLUSIONS Wholegrain cereal foods consumption compared with refined cereals for 12 weeks did not affect peripheral insulin sensitivity. The study was registered with ClinicalTrials.gov identifier NCT00945854.

Nutrition and oxidative stress: a systematic review of human studies

Oxidative stress (OS) – defined as the imbalance between free radical production and antioxidant defences – is a condition associated with chronic-degenerative disease, such as cancer, metabolic and disease cardiovascular diseases (CVDs). Several studies have shown that diet and some of its components could influence the intensity of OS damage. The aim of this review was to critically examine some pieces of evidence from observational and intervention study in human beings to assess whether diet and its components can really modify OS in vivo. Furthermore, we tried to find out the possible mechanism behind this association. We considered all studies in MEDLINE which fitted with the following criteria: (1) adult subjects who were healthy or affected by metabolic disease and CVDs; (2) no food supplements, pillows, powder but only common foods and beverages and (3) OS assessment with well-known and validated in vivo biomarkers.

Postprandial chylomicrons and adipose tissue lipoprotein lipase are altered in type 2 diabetes independently of obesity and whole-body insulin resistance

BACKGROUND AND AIMS Postprandial lipoprotein abnormalities in type 2 diabetes are associated with insulin resistance. The role of other diabetes-related factors is still not clear. The aim of this study is to differentiate the effects of whole-body insulin resistance, obesity, and type 2 diabetes on postprandial dyslipidaemia and lipoprotein lipase (LPL) in adipose tissue. METHODS AND RESULTS Ten subjects with obesity and diabetes (OD), 11 with obesity alone (O), and 11 normal-weight controls (C) - males, aged 26-59 years, with fasting normo-triglyceridaemia underwent measurements of cholesterol, triglycerides, apo B-48 and apo B-100 concentrations in plasma lipoproteins separated by density gradient ultracentrifugation before and after a fat-rich meal. Fasting and postprandial (6h) LPL activity was determined in abdominal subcutaneous adipose tissue biopsy samples. Insulin sensitivity was measured by hyperinsulinaemic euglycaemic clamp. OD and O subjects had similar degrees of adiposity (BMI, waist circumference, fat mass) and insulin resistance (insulin stimulated glucose disposal and M/I). They also showed a similarly higher postprandial increase in large VLDL lipids (triglyceride incremental AUC 188+/-28 and 135+/-22 mg/dl.6h) than C (87+/-13 mg/dl.6h, M+/-SEM, p<0.05). OD had an increased chylomicron response compared to O (triglyceride incremental AUC 132+/-23 vs. 75+/-14 mg/dl.6h, p<0.05). OD had significantly lower fasting and postprandial adipose tissue heparin-releasable LPL activity than O and C. CONCLUSIONS In insulin-resistant conditions of obesity, with and without diabetes, large VLDL are increased after a fat-rich meal. In addition, diabetic patients compared to obese subjects have an increased postprandial chylomicron response and a reduced adipose tissue LPL activity.

Effects of whole-grain cereal foods on plasma short chain fatty acid concentrations in individuals with the metabolic syndrome

OBJECTIVE Short chain fatty acids (SCFAs) derived from dietary fiber fermentation by gut microbiota have been identified as one of the mechanisms behind the association between habitual whole-grain intake and a lower risk of cardiometabolic diseases. The aims of the present work are: (1) to evaluate whether a whole-grain wheat-based diet may increase SCFAs concentration, and (2) to identify possible associations between SCFAs and metabolic changes observed after the nutritional intervention. METHODS Fifty-four subjects participated in the trial. They underwent a 12-wk dietary intervention based on whole-grain or refined cereal products. At baseline and after the intervention, glucose, insulin, triacylglycerol, inflammatory markers (hs-CRP, IL-1 ra, IL-6, and TNF-α), and SCFAs plasma concentrations were evaluated. RESULTS After the intervention, in the whole-grain group fasting plasma propionate concentrations were higher than at baseline, whereas a reduction was detected in the control group. The absolute changes (end of trial minus baseline) in fasting plasma propionate concentrations were significantly different between the two groups (P = 0.048). The absolute changes of fasting propionate correlated with cereal fiber intake (r = 0.358, P = 0.023), but no significant correlations with clinical outcomes were found. However, postprandial insulin was significantly decreased in the group having the absolute changes of fasting propionate concentration above the median value (P = 0.022 versus subjects with fasting propionate changes below the median value). CONCLUSIONS A 12-wk whole-grain wheat-based diet increases fasting plasma propionate. This increase correlates with the cereal fiber intake and is associated with lower postprandial insulin concentrations.

Fasting and post-prandial adipose tissue lipoprotein lipase and hormone-sensitive lipase in obesity and Type 2 diabetes

Background: Fasting and post-prandial abnormalities of adipose tissue (AT) lipoprotein lipase (LPL) and hormone-sensitive lipase (HSL) activities may have pathophysiological relevance in insulin-resistant conditions. Aim: The aim of this study was to evaluate activity and gene expression of AT LPL and HSL at fasting and 6 h after meal in two insulin-resistant groups — obese with Type 2 diabetes and obese without diabetes — and in non-diabetic normal-weight controls. Material/subjects and methods: Nine obese subjects with diabetes, 10 with obesity alone, and 9 controls underwent measurements of plasma levels of glucose, insulin, and triglycerides before and after a standard fat-rich meal. Fasting and post-prandial (6 h) LPL and HSL activities and gene expressions were determined in abdominal subcutaneous AT needle biopsies. Results: The diabetic obese subjects had significantly lower fasting and post-prandial AT heparin-releasable LPL activity than only obese and control subjects (p<0.05) as well as lower mRNA LPL levels. HSL activity was significantly reduced in the 2 groups of obese subjects compared to controls in both fasting condition and 6 h after the meal (p<0.05), while HSL mRNA levels were not different. There were no significant changes between fasting and 6 h after meal measurements in either LPL or HSL activities and gene expressions. Conclusions: Lipolytic activities in AT are differently altered in obesity and Type 2 diabetes being HSL alteration associated with both insulin-resistant conditions and LPL with diabetes per se. These abnormalities are similarly observed in the fasting condition and after a fat-rich meal.

How Well Can We Control Dyslipidemias Through Lifestyle Modifications

The role for lifestyle modifications to correct dyslipidemia(s) is reviewed. Dietary composition is crucial. Replacing saturated fat with MUFA or n-6 PUFA lowers plasma low-density lipoproteins (LDL) cholesterol and ameliorates the LDL/HDL ratio. Replacing saturated fat with carbohydrates has diverging effects due to the heterogeneity of carbohydrate foods. Diets rich in refined carbohydrates increase fasting and postprandial triglycerides, whereas the consumption of fiber-rich, low GI foods lowers LDL cholesterol with no detrimental effects on triglycerides. The role of polyphenols is debated: available evidence suggests a lowering effect of polyphenol-rich foods on postprandial triglycerides. As for functional foods, health claims on a cholesterol lowering effect of psyllium, beta-glucans and phytosterols are accepted by regulatory agencies. The importance of alcohol intake, weight reduction, and physical activity is discussed. In conclusion, there is evidence that lifestyle affects plasma lipid. A multifactorial approach including multiple changes with additive effects is the best option. This may also ensure feasibility and durability. The traditional Mediterranean way of life can represent a useful model.

Association between different dietary polyphenol subclasses and the improvement in cardiometabolic risk factors: evidence from a randomized controlled clinical trial

AbstractAims Due to their different chemical structures and metabolism, polyphenol subclasses may have specific impact on cardiometabolic risk factors. Our aim was to evaluate whether the intake of different polyphenol subclasses is associated with clinical outcomes beneficially improved by polyphenols in a nutritional trial performed by our group (postprandial lipid response, glucose homeostasis, early insulin secretion and oxidative stress).MethodsThe present study is a secondary analysis of a nutritional intervention study with a diet naturally rich in polyphenols. The data are derived from 78 participants at high cardiovascular risk who completed the ETHERPATH trial. The associations between variations in polyphenol subclasses (phenolic acids, anthocyanidins, flavones, flavan-3-ols, flavonols and flavanones) and clinical outcomes beneficially influenced by polyphenols were firstly explored by Spearman’s correlation. Thereafter, adjustment for gender, age and body mass index (BMI) was run. Linear regression analysis was used to assess the class of polyphenols that best predicted the outcome. ResultsFlavanone intake was inversely correlated with postprandial lipid response, whereas flavone intake was related to postchallenge glucose response. Anthocyanidins and flavan-3-ols associated positively with early insulin secretion. The decrease in urinary isoprostanes correlated with anthocyanidins, flavan-3-ols and flavonols. Correlations did not change after adjustment for gender, age, and BMI. Linear regression analysis showed an independent association between flavonols and urinary isoprostanes, whereas early insulin secretion was mainly associated with flavan-3-ols intake. ConclusionsThe results of this study show that a polyphenol-rich diet may have a pleiotropic effect on cardiometabolic risk factors thanks to the specific action of different polyphenol subclasses.

Bioavailability and pharmacokinetic profile of grape pomace phenolic compounds in humans.

Grape pomace, the major byproduct of the wine and juice industry, is a relevant source of bioactive phenolic compounds. However, polyphenol bioavailability in humans is not well understood, and the inter-individual variability in the production of phenolic metabolites has not been comprehensively assessed to date. The pharmacokinetic and excretive profiles of phenolic metabolites after the acute administration of a drink made from red grape pomace was here investigated in ten volunteers. A total of 35 and 28 phenolic metabolites were quantified in urine and plasma, respectively. The main circulating metabolites included phenyl-γ-valerolactones, hydroxybenzoic acids, simple phenols, hydroxyphenylpropionic acids, hydroxycinnamates, and (epi)catechin phase II conjugates. A high inter-individual variability was shown both in urine and plasma samples, and different patterns of circulating metabolites were unravelled by applying unsupervised multivariate analysis. Besides the huge variability in the production of microbial metabolites of colonic origin, an important variability was observed due to phase II conjugates. These results are of interest to further understand the potential health benefits of phenolic metabolites on individual basis.