Effects of a diet naturally rich in polyphenols on lipid composition of postprandial lipoproteins in high cardiometabolic risk individuals: an ancillary analysis of a randomized controlled trial.

BACKGROUND/OBJECTIVES: Plasma lipoprotein composition, especially in the postprandial state, could be relevant for cardiovascular risk and could be influenced by eating habits. This study evaluated the effects of a polyphenol-rich diet on postprandial lipoprotein composition in individuals at high cardiometabolic risk. SUBJECTS/METHODS: Seventy-eight individuals with high waist circumference and at least another component of the metabolic syndrome were randomized to either a high-polyphenol (HighP) or low-polyphenol (LowP) diet. Before and after the 8-week intervention, chylomicrons, VLDL1, VLDL2, IDL, LDL, HDL particles, and their lipid concentrations were determined over a 6-h high-fat test meal with high or low-polyphenol content, according to the diet assigned. RESULTS: VLDL1 postprandial areas under the curve (AUCs) were lower for cholesterol (Chol) (1.48 ± 0.98 vs. 1.91 ± 1.13 mmol/L × 6 h, M ± SD, p = 0.014) and triglycerides (Tg) (4.70 ± 2.70 vs. 6.02 ± 3.07 mmol/L × 6 h, p = 0.005) after the HighP than after the LowP diet, with no changes in Chol/Tg ratio. IDL Chol AUCs were higher after the HighP than after the LowP diet (1.29 ± 0.77 vs. 1.01 ± 0.51 mmol/L × 6 h, p = 0.037). LDL Tg AUCs were higher after the HighP than after the LowP diet (1.15 ± 0.33 vs. 1.02 ± 0.35 mmol/L × 6 h, p < 0.001), with a lower Chol/Tg ratio (14.6 ± 4.0 vs. 16.0 ± 3.8, p = 0.007). HDL Tg AUCs were lower after the HighP than after the LowP diet (1.20 ± 0.41 vs. 1.34 ± 0.37 mmol/L × 6 h, p = 0.013). CONCLUSIONS: A high-polyphenol diet reduces the postprandial lipid content of large VLDL and increases IDL cholesterol; it modifies the composition of LDL particles-which become richer in triglycerides, and of HDL-which become instead triglyceride poor. The overall changes in atherogenicity by these effects warrant further investigation on clinical cardiovascular outcomes.

Isoenergetic diets differing in their n-3 fatty acid and polyphenol content reflect different plasma and HDL-fraction lipidomic profiles in subjects at high cardiovascular risk.

SCOPE: Dysregulation of lipid homeostasis is related to multiple major healthcare problems. The aim of this study was to investigate the effects of n-3 fatty acid (FA) and polyphenol rich diets on plasma and HDL fraction lipidomic profiles in subjects at high cardiovascular risk. METHODS AND RESULTS: Ultra performance LC coupled to quadrupole TOF/MS mass spectrometry global lipidomic profiling was applied to plasma and HDL fraction from an 8 wk randomized intervention with four isoenergetic diets, differing in their natural n-3 FA and polyphenols content, in 78 subjects with a high BMI, abdominal obesity, and at least one other feature of the metabolic syndrome. Dependency network analysis showed a different pattern of associations between lipidomics, dietary, and clinical variables after the dietary interventions. The most remarkable associations between variables were observed after the diet high in n-3 FA and polyphenols, as the inverse association between gallic acid intake and LDL cholesterol levels, which was indirectly associated with a HDL cluster exclusively comprised lysophospholipids. CONCLUSION: This is the first human randomized controlled trial showing direct and indirect associations with lipid molecular species and clinical variables of interest in the evaluation of the metabolic syndrome after diets naturally rich in polyphenols.

Fasting apolipoprotein B48 is associated with asymptomatic peripheral arterial disease in type 2 diabetic subjects: a case-control study.

OBJECTIVE: To test whether there is an association between fasting ApoB48 level, a marker of the residual presence of intestinally derived TRLs lipoproteins, thought to be highly atherogenic, and peripheral artery disease (PAD) in type 2 diabetic patients independent of fasting plasma lipids. METHODS: We studied 87 patients with type 2 diabetes: 34 with asymptomatic PAD (ankle/brachial index < 0.9) and 53 without PAD matched on age (±2 years), gender and BMI (±2 kg/m(2)). The plasma fasting ApoB48 was measured by ELISA. RESULTS: Patients with PAD had significantly higher ApoB48 levels (1.529 ± 1.253 vs 1.095 ± 0.667 µg/ml p = 0.04) than those without PAD independent of major confounders, such as duration of diabetes, smoking status, HbA1c, systolic blood pressure and fasting plasma lipids. CONCLUSIONS: Fasting ApoB48 was independently associated with asymptomatic PAD in patients with type 2 diabetes.

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

BACKGROUND: The 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 METHODS: The levels of anandamide and 2-AG, and of the anandamide-related PPARalpha 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. RESULTS: As 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. CONCLUSIONS: The 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.

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.