Metabolic fitness in relation to genetic variation and leukocyte DNA methylation.

Metabolic syndrome (MetS) is a highly prevalent condition causing increased risk of several life-threatening diseases. MetS has a pronounced hereditary basis but is also influenced by environmental factors, partly through epigenetic mechanisms. In this study, the five phenotypes underlying MetS were incorporated into a continuous score for metabolic fitness (MF), and associations with both genotypic variation and leukocyte DNA methylation were investigated. Baseline MF phenotypes (waist circumference, blood pressure, blood glucose, serum triglycerides, and high-density lipoproteins) of 710 healthy Flemish adults were measured. After a 10 yr period, follow-up measures were derived from 618 of these subjects. Genotyping was performed for 65 preselected MF-related genetic variants. Next, full genetic predisposition scores (GPSs) were calculated, combining genotype scores of multiple genetic variants. Additionally, stepwise GPSs were constructed, including only the most predictive genetic variants for the different MF phenotypes. For a subset of 68 middle-aged men, global and gene-specific DNA methylation was investigated, and a biological pathway analysis was performed. The full GPSs were predictive for some baseline MF phenotypes, but not for changes over time. Only a limited number of genetic variants were significantly predictive individually. On the contrary, global and gene-specific DNA methylation was associated with changes in the MF phenotypes rather than with the baseline measures, indicating that effects of DNA methylation on MF are somewhat delayed. Furthermore, several biological pathways were associated with the MF phenotypes through gene promoter methylation. For CETP, G6PC2, MC4R, and TFAP2B both a genetic and epigenetic relationship was found with MF.

Relation between sugar-sweetened beverage consumption and micronutrient intake in a prospective study.

Micronutrient dilution following sugar-sweetened beverage (SSB) consumption can lead to a qualitative impoverishment of a dietary pattern. The aim of this prospective study was to investigate the relation between SSB consumption and micronutrients. A total 562 adults were tested in 2002 and 2012 for the same anthropometric, lifestyle and nutritional intake activity parameters. Calcium, iron and magnesium intake decreased with increasing baseline SSB intake, and with increasing SSB consumption during the 10 years. A 100 ml increase in SSB consumption was associated with a 22 mg lower intake of calcium, 0.4 mg of iron and 9 mg of magnesium. There was no relation between vitamins and SSB consumption. In conclusion, there was limited evidence in our study, which suggests SSB have minimal dilutional effect on dietary micronutrient consumption. A major limitation of the present study is that of the original 1569 participants in 2002, 36% returned for participation in 2012.

Stability of physical activity, fitness components and diet quality indices.

BACKGROUND: Regular physical activity (PA), a high level of fitness and a high diet quality are positively associated with health. However, information about stability of fitness components and diet quality indices is limited. This study aimed to evaluate stability of those parameters. METHODS: This study includes 652 adults (men=57.56 (10.28) years; women=55.90 (8.34) years at follow-up) who participated in 2002-2004 and returned for follow-up at the Policy Research Centre Leuven in 2012-2014. Minutes sport per day and Physical activity level (PAL) were calculated from the Flemish Physical Activity Computerized Questionnaire. Cardiorespiratory fitness (CRF), morphological fitness (MORF; body mass index and waist circumference) and metabolic fitness (METF) (blood cholesterol and triglycerides) were used as fitness components. Diet quality indices (Healthy Eating Index-2010 (HEI), Diet Quality Index (DQI), Mediterranean Diet Score (MDS)) were calculated from a diet record. Tracking coefficients were calculated using Pearson/Spearman correlation coefficients (rPearson) and intra-class correlation coefficients (rICC). RESULTS: In both men (rPearson&ICC=0.51) and women (rPearson=0.62 and rICC=0.60) PAL showed good stability, while minutes sport remained stable in women (rPearson&ICC=0.57) but less in men (rPearson&ICC=0.45). Most fitness components remained stable (r⩾0.50) except some METF components in women. In general the diet quality indices and their components were unstable (r<0.50). CONCLUSIONS: PAL and the majority of the fitness components remained stable, while diet quality was unstable over 10 years. For unstable parameters such as diet quality measurements are needed at both time points in prospective research.

Nature of the antiadrenergic properties of an indolizine.

Inhibition by 2-ethyl-3-(4-y-di-n-butylaminopropoxybenzoyl)-indolizine hydrochloride (L 9394) and by propranolol of the positive chronotropic effect of isoproterenol on spontaneously beating rabbit right atria has been studied in vitro. Propranolol behaved like a typical competitive beta 1-adrenoceptor antagonist with a pA2 value of 8.33. L 9394 acted as a non-competitive inhibitor with a pD'2 value of about 4.98. Inhibition by L 9394 and phentolamine of the norepinephrine-induced contractions of isolated rat aortic strips has been studied likewise. Phentolamine inhibited the adrenergic alpha-adrenoceptor competitively with a pA2 value of 8.69 while L 9394 behaved like a dual inhibitor, with a competitive component (pA2 value of 6.35) and a non-competitive component (pD'2 value of about 4.72).

Amiodarone-like haemodynamic and non-competitive antiadrenergic properties of a benzoyl-indolizine.

1. 2-Ethyl-3-(4-gamma-di-n-butylaminopropoxy-benzoyl)-indolizine hydrochloride (L 9394) induced in the ananesthetized dog a marked and long-lasting decrease in heart rate together with a transient reduction in blood pressure. 2. L 9394 decreased Robinson's index, an effect which suggests that the substance reduces the oxygen requirements of the heart. 3. L 9394 markedly increased coronary arterial blood flow. 4. L 9394 is endowed with non-competitive antiadrenergic properties. 5. L 9394 did not impair cardiac function since cardiac output and stroke volume increased appreciably during the initial phase of action and did not fall below the control values at any time thereafter. 6. The overall haemodynamic properties of L 9394, which were similar to those of amiodarone, are considered to be potentially valuable for the long-term treatment of angina pectoris.

Nature of the inhibition by amiodarone of isoproterenol-induced tachycardia in the dog.

Inhibition of in vivo isoproterenol-induced tachycardia by i.v. amiodarone was studied in anesthetized dogs. Significant dose-response curves to isoproterenol could not be obtained in single animals because of the time-dependent lowering of the inhibitory effect of the drug. Single isoproterenol injections after amiodarone in 105 dogs allowed dose-response curves to be obtained. The slope of these curves decreased with increasing doses of amiodarone, and the maximal rate stimulation diminished also in a dose-dependent manner. These features are consistent with a non-competitive inhibition pattern. A mechanism of the beta-adrenergic antagonism developed by amiodarone is suggested.

A potentially antianginal benzo [b]thiophene with an amiodarone-like haemodynamic profile.

L 9146 or 2-methyl-3(3,5 dimethyl-4-gamma-di-n-butylaminopropoxy-benzoyl)-benzo [b] thiophene is a substance belonging to the amiodarone series which induces in the anaesthetized dog a decrease of myocardial oxygen consumption which is mainly due to slowing of the heart rate and reduction in systemic blood pressure. L 9146 also enhances coronary blood flow. L 9146 has also antiadrenergic properties since catecholamine-induced hypertension, tachycardia and increase of myocardial oxygen consumption are markedly antagonized; these antiacrenergic effects are not due to a competitive blockade of the beta-adrenoceptors. L 9146 does not decrease cardiac output, but increases it appreciably in the initial phase of its action. Several findings indicate that when the intensity of certain properties is considered, l9146 is more active than aniodarone since only half the dose used with aniodarone is required to achieve a given level of action. The overall haemodynamic properties of L 9146, which are similar to those of amiodarone, are considered to be potentially valuable for the long-term treatment of angina pectoris.