Influence of Interesterification of a Stearic Acid-Rich Spreadable Fat on Acute Metabolic Risk Factors

Chemical and enzymatic interesterification are used to create spreadable fats. However, a comparison between the two processes in terms of their acute metabolic effects has not yet been investigated. A randomised crossover study in obese (plasma TAG > 1.69 mmol/L, and BMI > 30 (BMI = kg/m²) or waist circumference > 102 cm, n = 11, age = 59.3 ± 1.8 years) and non-obese (plasma triacylglycerol (TAG) < 1.69 mmol/L, and BMI < 30  or waist circumference < 102 cm, n = 10, age = 55.8 ± 2.2 years) men was undertaken to compare the effects of chemical versus enzymatic interesterification on postprandial risk factors for type 2 diabetes (T2D) and cardiovascular disease (CVD). TAG, cholesterol, glucose, insulin and free fatty acid concentrations were measured for 6 h following consumption of 1 g fat/kg body mass of non-interesterified (NIE), chemically interesterified (CIE), enzymatically interesterified (EIE) stearic acid-rich fat spread or no fat, each with 50 g available carbohydrate from white bread. Interesterification did not affect postprandial glucose, insulin, free fatty acids or cholesterol (P > 0.05). Following ingestion of NIE, increases in serum oleic acid were observed, whereas both oleic and stearic acids were increased with CIE and EIE (P < 0.05). While postprandial TAG concentrations in non-obese subjects were not affected by fat treatment (P > 0.05), obese subjects had an 85% increase in TAGs with CIE versus NIE (P < 0.05). The differences in TAG response between non-obese and obese subjects suggest that interesterification may affect healthy individuals differently compared to those already at risk for T2D and/or CVD.     

Grape skin extract inhibits mammalian intestinal α-glucosidase activity and suppresses postprandial glycemic response in streptozocin-treated mice

Intestinal α-glucosidases are the key enzymes responsible for starch digestion and absorption and their inhibition has been proven effective in both preventing and treating diabetes through improvement of postprandial hyperglycaemia. This study, for the first time, identified that a Norton grape skin extract (GSE) significantly inhibited mammalian intestinal α-glucosidases but not other digestive enzymes including structurally relevant pancreatic α-amylase. Norton GSE inhibited rat intestinal α-glucosidases through a competitive mode with an IC₅₀ of 0.384 mg/ml. Further animal study revealed that the oral intake of Norton GSE (400 mg/kg) significantly reduced postprandial blood glucose by 30.9% in the streptozocin-treated male C57BL/6 J mice following starch challenge. These findings suggest that Norton GSE may have a unique property of suppressing postprandial blood glucose through a mechanism involving the inhibition of α-glucosidases, thereby providing a novel dietary opportunity for diabetes management.     

Effect of Dietary Cholesterol and Fat on Cell Cholesterol Transfer to Postprandial Plasma in Hyperlipidemic Men

Postprandial chylomicrons are potent ultimate acceptors of cell membrane cholesterol and are believed to accelerate reverse cholesterol transport (RCT). We compared the effects of meals rich in polyunsaturated fat (PUFA) and either high (605 mg) or low (151 mg) in cholesterol and a meal rich in dairy fat (DF) in the form of cream on net in vitro transport of red blood cell (RBC) membrane cholesterol to 4 and 6 h postprandial plasma in eight normotriglyceridemic (NTG-H) and eight hypertriglyceridemic (HTG-H) men with mild to moderate hypercholesterolemia. In HTG-H men, cell cholesterol accumulation in 6-h postprandial plasma was significantly (P = 0.02) less after the PUFA-HC meal compared with the other meals. The significant (P < 0.001) increase in cell plus endogenous cholesterol accumulation in the triglyceride-rich lipoprotein (TRL) fraction of 4 h postprandial plasma incubated with RBC was significantly (P = 0.007) higher after the PUFA-HC meal compared with DF meal in HTG-H men. In NTG-H men, cholesterol accumulation in plasma and plasma lipoproteins in the presence and absence of RBC was not significantly affected by the type of meal ingested. These data suggest that addition of large amounts of cholesterol to a PUFA meal may impair diffusion-mediated transport of cell membrane cholesterol to postprandial plasma and that replacing DF with PUFA in a meal increases postprandial lipemia and may potentially increase cholesterol accumulation in atherogenic postprandial TRL in HTG-H men.     

The L513S polymorphism in medium-chain acyl-CoA synthetase 2 (MACS2) is associated with risk factors of the metabolic syndrome in a Caucasian study population

Enzymes of the medium-chain acyl-CoA synthetase (MACS) family catalyze the ligation of medium chain fatty acids with CoA to produce medium-chain-acyl-CoA. At least four members of the MACS gene family are clustered on human chromosome 16p12. Association studies in the Japanese Suita cohort of MACS polymorphisms and various phenotypes revealed the contribution of the Leu513Ser polymorphism in MACS2 to multiple risk factors of the metabolic syndrome. Here, we investigated the association between this polymorphism and different risk factors in the Caucasian Metabolic Intervention Cohort Kiel. Seven hundred and sixteen male subjects aged 45-65 years were recruited for a standard oral glucose tolerance test and the postprandial assessment of metabolic parameters after an oral metabolic tolerance test (oMTT; 1017 kcal, 51.6% fat, 29.6% carbohydrates, 11.9% protein). The MACS2 Leu513Ser polymorphism was determined by TaqMan-Assay in 705 subjects. Postprandial triglyceride levels following oMTT [area under the curve (AUC)] were significantly higher in subjects carrying the Ser allele compared to subjects homozygous for the Leu allele (1690 +/- 100 mg x h/dL versus 1514 +/- 39 mg x h/dL, p = 0.04). Significant differences between genotype groups were also found for fasting (108 +/- 1.9 mg/dL versus 104 +/- 0.66 mg/dL, p = 0.04) and postprandial (AUC 535 +/- 11 versus 512 +/- 4.0, p = 0.02) glucose levels as well as for high-density-lipoprotein, body mass index, waist circumference, systolic and diastolic blood pressure. Carriers of the Ser allele also show an increased risk of impaired glucose metabolism (OR: 1.48, 95% confidence interval: 0.98-2.27, p = 0.07), adiposity (1.8, 1.16-2.81, p = 0.01) and hypertension (1.5, 0.99-2.17, p = 0.06). In conclusion, our results suggest an involvement of the MACS2 Leu513Ser polymorphism in the development of the metabolic syndrome in Caucasian population. Additionally, the higher triglyceride and glucose levels after an oMTT support a possible functional impact of the polymorphism in vivo.     

Antihyperglycemic activity of polyphenolic components of black/bitter cumin <Emphasis Type="Italic">Centratherum anthelminticum</Emphasis> (L.) Kuntze seeds

The effect of black/bitter cumin seeds Centratherum anthelminticum (L.) Kuntze extract (CA) containing mixture of polyphenolic compounds was tested on rat intestinal α-glucosidases, human salivary α-amylase activity and postprandial hyperglycemia in rats. Polyphenolic components of C. anthelminticum seeds (CA) dose dependently inhibited rat intestinal disaccharidases. IC₅₀ values were found to be 34.1 ± 3.8, 62.2 ± 4.5 and 500.5 ± 11.9 μg of CA for rat intestinal sucrase, maltase and p-nitrophenyl α-d-glucopyranoside (PNP-glycoside), respectively. CA also inhibited human salivary α-amylase activity with IC₅₀ value of 185.5 ± 4.9 μg. The inhibitory effect of CA was found to be 8–32 fold more potent than dl-catechin but less effective than acarbose on rat intestinal disaccharidases and salivary α-amylase. The enzyme kinetic studies showed a non-competitive type of inhibition with a low K _i value of 30.24 μg, 76.67 μg and 341.60 μg of CA for maltase, sucrase and PNP-glycoside hydrolysis activities, respectively. The in vitro inhibition of glucosidases was further confirmed by in vivo maltose tolerance test in rats. Feeding of CA at 50–200 mg/kg body weight (b.wt) to maltose (2.0 g/kg b.wt), loaded rats significantly reduced the postprandial plasma glucose levels compared with acarbose. The inhibitory components of CA were identified as a mixture of polyphenolic compounds viz., gallic acid, protocatechuic acid, caffeic acid, ellagic acid, ferulic acid, quercetin and kaempferol. This study demonstrated that CA exerts antihyperglycemic effect by decreasing postprandial glucose in rats by modulating α- amylase and glucosidases (sucrase and maltase) activity and thus may be useful for the management of diabetes mellitus.     

An Oral Mixed Fat Load Is Followed by a Modest Anti-inflammatory Adipocytokine Response in Overweight Patients with Metabolic Syndrome

We investigated the postprandial changes in plasma levels of adipocytokines in overweight patients with metabolic syndrome after an oral fat load. After an oral fat load and during a prolonged fast, blood was drawn at 0, 2, 3, 4 and 8 h for measurement of adiponectin, adipsin, cathepsin S, chemerin, hepatic growth factor, interferon‐γ‐inducible protein‐10, leptin, macrophage chemoattractant protein‐1, macrophage migration inhibitory factor, nerve growth factor, retinol binding protein‐4, resistin, serum amyloid A1, tissue inhibitor of metalloproteinase‐1 and thrombopoietin using a microbead‐based Luminex assay. Area under the curves (AUC) were calculated and compared. Plasma adiponectin levels were higher after an oral fat load compared to fasting at t = 2 h (950 ± 513 vs. ?1,881 ± 713 ng/ml) while the plasma levels for adipsin (?9 ± 5 vs. 16 ± 5 ng/ml), chemerin (?122 ± 35 vs. 13 ± 21 ng/ml), SAA‐1 (?391 ± 213 vs. 522 ± 173 ng/ml) and TPO (?335 ± 144 vs. 622 ± 216 ng/ml) were lower after an oral fat load compared to fasting. The baseline corrected AUC for IP‐10 was higher after fat load compared to fasting (median ?116 pg h/ml; IQR ?270 to 10 vs. ?21 pg h/ml; IQR ?136 to 418 (p = 0.047). In conclusion, in overweight male subjects with the metabolic syndrome, an oral fat load is accompanied with a modest anti‐inflammatory response of adipose tissue‐derived adipocytokines.