Biomedical subjects

Ellen E Blaak

Publications and source records attributed to Ellen E Blaak.

13 recordsLinked to original sources

PubMed2007

Endocrine role of the renin-angiotensin system in human adipose tissue and muscle: effect of beta-adrenergic stimulation.

The renin-angiotensin system has been implicated in obesity-related hypertension and insulin resistance. We examined whether locally produced components of the renin-angiotensin system in adipose tissue and skeletal muscle play an endocrine role in vivo in humans. Furthermore, the effects of beta-adrenergic stimulation on plasma concentrations and tissue release of renin-angiotensin system components were investigated. Systemic renin-angiotensin system components and arteriovenous differences of angiotensin II (Ang II) and angiotensinogen (AGT) across abdominal subcutaneous adipose tissue and skeletal muscle were assessed in combination with measurements of tissue blood flow before and during systemic beta-adrenergic stimulation in 13 lean and 10 obese subjects. Basal plasma Ang II and AGT concentrations were not significantly different between lean and obese subjects. Ang II concentrations were increased in obese compared with lean subjects during beta-adrenergic stimulation (12.6+/-1.5 versus 8.1+/-1.0 pmol/L; P=0.04), whereas AGT concentrations remained unchanged. Plasma renin activity increased to a similar extent in lean and obese subjects during beta-adrenergic stimulation (both P<0.01). No net Ang II release across adipose tissue and skeletal muscle could be detected in both groups of subjects. However, AGT was released from adipose tissue and muscle during beta-adrenergic stimulation in obese subjects (both P<0.05). In conclusion, locally produced Ang II in adipose tissue and skeletal muscle exerts no endocrine role in lean and obese subjects. In contrast, AGT is released from adipose tissue and muscle in obese subjects during beta-adrenergic stimulation, which may contribute to the increased plasma Ang II concentrations during beta-adrenergic stimulation in obese subjects.

Abdomen↗

PubMed2007

Preferential uptake of dietary Fatty acids in adipose tissue and muscle in the postprandial period.

Despite consistent evidence that abnormalities of fatty acid delivery and storage underlie the metabolic defects of insulin resistance, physiological pathways by which fat is stored in adipose tissue and skeletal muscle are not clear. We used a combination of stable isotope labeling and arteriovenous difference measurements to elucidate pathways of postprandial fat deposition in adipose tissue and skeletal muscle in healthy humans. A test meal containing [U-(13)C]palmitate was combined with intravenous infusion of [(2)H(2)]palmitate to label plasma fatty acids and VLDL-triglyceride. Both dietary (chylomicron) and VLDL-triglyceride were cleared across adipose tissue and muscle, though with greater fractional extraction of the chylomicron-triglyceride. In adipose tissue there was significant uptake of plasma nonesterified fatty acids (NEFAs) in the postprandial but not the fasting state. However, this was minor in comparison with chylomicron-triglyceride fatty acids. We modeled the fate of fatty acids released by lipoprotein lipase (LPL). There was clear preferential uptake of these fatty acids compared with plasma NEFAs. In muscle, there was unexpected evidence for release of LPL-derived fatty acids into the plasma. With this integrative physiological approach, we have revealed hidden complexities in pathways of fatty acid uptake in adipose tissue and skeletal muscle.

Abdomen↗

PubMed2006

Genotype-by-nutrient interactions assessed in European obese women. A case-only study.

BACKGROUND: The development of obesity is influenced by both genetic and environmental risk factors. Whereas changes in the environment appear to be responsible for the increasing prevalence of obesity, genetic factors interacting with environmental factors would contribute to explain obesity onset and severity. AIM: To explore epidemiologic genotype-by-nutrient interactions in obesity. METHODS: A total of 42 polymorphisms of 26 candidate genes for obesity were genotyped in 549 adult obese women recruited from eight European centres in a case-only study. The nutritional variables assessed in this study were the dietary fibre intake (grams per day), the ratio of dietary polyunsaturated fat to saturated fat (P:S ratio) and the percentage of energy derived from fat in the diet as calculated from a weighed three-day food record (%E). Under the assumption of genotype-nutrient independence in the population, the odds ratio calculated in a sample of obese women would indicate the existence of genotype-by-nutrient interactions, measured as deviations from the multiplicative effects of the genetic and the nutrient factors separately. RESULTS: No new but confirmaty evidences for genotype-by-nutrient interactions in obesity were detected in this case-only study. The test of interaction between fibre intake and the -514 C > T polymorphism of the hepatic lipase gene (LIPC) yielded P-values of 0.01 across different statistical models. Likewise, the -11377G > C polymorphism of the adiponectin gene (ADIPOQ) and the -681 C > G polymorphism of the PPARG3 gene might interact with the percentage of energy derived from fat in the diet for the development of obesity (P-values in the range of 0.01-0.05 across different statistical models). The P-values were not adjusted for multiple testing, so these results should be considered with caution. CONCLUSIONS: Although the use of obese-only samples is theoretically a useful approach to detect interactions, few genotype-by-nutrient interactions have been suggested in obese European women after the analysis of candidate polymorphisms and the selected nutrient variables. The most remarkable multiplicative interaction found in this study refers to the combination of the hepatic lipase gene polymorphism -514 C > T and fibre intake.

Adiponectin↗

PubMed2006

Fat oxidation before and after a high fat load in the obese insulin-resistant state.

BACKGROUND: Obesity may be associated with a lowered use of fat as a fuel, which may contribute to the enlarged adipose tissue stores. AIM: The aim of the present study was to study fatty acid use in the fasting state and in response to a high fat load in a large cohort of obese subjects (n = 701) and a lean reference group (n = 113). METHODS: Subjects from eight European centers underwent a test meal challenge containing 95 en% fat [energy content 50% of estimated resting energy expenditure (EE)]. Fasting and postprandial fat oxidation and circulating metabolites and hormones were determined over a 3-h period. RESULTS: Postprandial fat oxidation (as percent of postprandial EE, adjusted for fat mass, age, gender, center, and energy content of the meal) decreased with increasing body mass index (BMI) category (P < 0.01), an effect present only in those obese subjects with a relatively low fasting fat oxidation (below median, interaction BMI category x fasting fat oxidation, P < 0.001). Fasting fat oxidation increased with increasing BMI category (P < 0.001), which was normalized after adjustment for fat-free mass and fat mass. Furthermore, insulin resistance was positively associated with postprandial fat oxidation (P < 0.05) and negatively associated with fasting fat oxidation (expressed as percent of EE), independent of body composition. CONCLUSIONS: The present data indicate an impaired capacity to regulate fat oxidation in the obese insulin-resistant state, which is hypothesized to play a role in the etiology of both obesity and insulin resistance.

Adult↗

PubMed2005

Reduced skeletal muscle uncoupling protein-3 content in prediabetic subjects and type 2 diabetic patients: restoration by rosiglitazone treatment.

CONTEXT: The mitochondrial uncoupling protein-3 (UCP3) has been implicated in the protection of the mitochondrial matrix against lipid-induced mitochondrial damage. Recent evidence points toward mitochondrial aberrations as a major contributor to the development of insulin resistance and diabetes, and UCP3 is reduced in diabetes. OBJECTIVE: We compared skeletal muscle UCP3 protein levels in prediabetic subjects [i.e. impaired glucose tolerance (IGT)], diabetic patients, and healthy controls and examined whether rosiglitazone treatment was able to restore UCP3. PATIENTS, DESIGN, INTERVENTION: Ten middle-aged obese men with type 2 diabetes mellitus [age, 61.4 +/- 3.1 yr; body mass index (BMI), 29.8 +/- 2.9 kg/m(2)], nine IGT subjects (age, 59.0 +/- 6.6 yr; BMI, 29.7 +/- 3.0 kg/m(2)), and 10 age- and BMI-matched healthy controls (age, 57.3 +/- 7.4 yr; BMI, 30.1 +/- 3.9 kg/m(2)) participated in this study. After baseline comparisons, diabetic patients received rosiglitazone (2 x 4 mg/d) for 8 wk. MAIN OUTCOME MEASURES: Muscle biopsies were sampled to determine UCP3 and mitochondrial protein (complex I-V) content. RESULTS: UCP3 protein content was significantly lower in prediabetic IGT subjects and in diabetic patients compared with healthy controls (39.0 +/- 28.5, 47.2 +/- 24.7, and 72.0 +/- 23.7 arbitrary units, respectively; P < 0.05), whereas the levels of the mitochondrial protein complex I-V were similar between groups. Rosiglitazone treatment for 8 wk significantly increased insulin sensitivity and muscle UCP3 content (from 53.2 +/- 29.9 to 66.3 +/- 30.9 arbitrary units; P < 0.05). CONCLUSION: We show that UCP3 protein content is reduced in prediabetic subjects and type 2 diabetic patients. Eight weeks of rosiglitazone treatment restores skeletal muscle UCP3 protein in diabetic patients.

Aged↗

PubMed2005

Postprandial interleukin-6 release from skeletal muscle in men with impaired glucose tolerance can be reduced by weight loss.

CONTEXT: Obesity and type 2 diabetes mellitus are associated with increased levels of IL-6, a marker of inflammation. OBJECTIVE: This study addressed the question of whether IL-6 was released from skeletal muscle after a high-fat meal in men with impaired glucose tolerance (IGT), a prediabetic state, and whether IL-6 release could be reduced by weight loss. DESIGN: Skeletal muscle metabolism was studied in men with IGT (n = 11) and compared with men with normal glucose tolerance (NGT, n = 9), matched for body mass index and age. IL-6 flux over skeletal muscle was measured with the forearm model. Eight IGT men were willing to participate in a 12-wk weight loss program and were tested again. RESULTS: IL-6, but not C-reactive protein or TNF-alpha receptor 1 and 2, was released by skeletal muscle. Muscle IL-6 release was higher in IGT than in NGT during fasting (IGT = 2.26 +/- 1.89 vs. NGT = 0.87 +/- 0.48 fmol x 100 ml tissue(-1) x min(-1), P = 0.04) and after a meal (mean area under the curve per minute: IGT = 3.48 +/- 2.63 vs. NGT = 1.37 +/- 0.75 fmol x 100 ml tissue(-1) x min(-1); P = 0.03). In the IGT men, body weight loss resulted in a decrease of postprandial IL-6 release from skeletal muscle (-52%; P = 0.04), reaching levels of the obese, NGT controls. CONCLUSION: The present data suggest that a high-fat meal can evoke IL-6 release from muscle and that the IL-6 release is a consequence rather than a cause of the obese, insulin-resistant, and/or IGT state.

Aged↗

PubMed2005

Metabolic fluxes in skeletal muscle in relation to obesity and insulin resistance.

The present article addresses the hypothesis that inefficient skeletal muscle lipid utilization may relate to the development of obesity and insulin resistance. In practice, there is evidence of impaired muscle fatty acid utilization in the obese state, and studies indicate that differences in muscle fatty acid oxidative capacity might play a role in the pathogenesis of obesity. The link between obesity and insulin resistance has been recognized for many years. There is accumulating evidence that a disturbed muscle fat oxidative capacity results in the accumulation of the lipid intermediates diacylglycerol and Fatty acid acyl coenzyme A (CoA), which may interfere with insulin signaling and result in an inhibition of insulin-mediated glucose uptake. Underlying mechanisms for disturbed fatty acid handling may relate to impaired adipose tissue lipolysis, abnormal muscle fatty acid uptake and a reduced ability to oxidize fat. Many of these abnormalities have been reported both in the obese and the type 2 diabetic state. The role of obesity per se in these disturbances is an important question that needs to be addressed.

Adipose Tissue↗

PubMed2005

Lifestyle intervention and fatty acid metabolism in glucose-intolerant subjects.

OBJECTIVE: Free fatty acid (FFA) oxidation is reduced in subjects with type 2 diabetes mellitus and impaired glucose tolerance (IGT). Weight reduction does not improve these impairments. Because exercise training is known to increase fatty acid (FA) oxidation, we investigated whether a combined diet and physical activity intervention program can improve FA oxidation in subjects with IGT. RESEARCH METHODS AND PROCEDURES: Sixteen subjects with IGT were studied before and after 1 year of a lifestyle intervention program [nine intervention (INT) subjects, seven controls (CON)]. INT subjects received regular (i.e., every 3 months) dietary advice and were stimulated to increase their level of physical activity. Glucose tolerance, anthropometric characteristics, and substrate use at rest and during exercise were evaluated before and after 1 year. Substrate oxidation was measured at rest and during moderate intensity exercise using indirect calorimetry in combination with stable isotope infusion ([U-(13)C]palmitate and [6,6-(2)H(2)-]glucose). RESULTS: After 1 year, no differences were seen in substrate use at rest. During exercise, total fat and plasma FFA oxidation were slightly increased in the INT group and decreased in the CON group, with the change being significantly different (change after 1 year: INT, +2.0 +/- 1.4 and +1.9 +/- 0.9 micromol/kg per minute; CON, -3.5 +/- 1.6 and -1.8 +/- 0.5 micromol/kg per minute for total and plasma FFA, respectively; p < 0.05). DISCUSSION: A combined diet and physical activity intervention program can prevent further deterioration of impaired FA oxidation during exercise in subjects with IGT.

Diabetes Mellitus, Type 2↗

PubMed2004

Validation of capillary glucose measurements to detect glucose intolerance or type 2 diabetes mellitus in the general population.

BACKGROUND: The use of an oral glucose tolerance test (OGTT) has been recommended to diagnose type 2 diabetes, but an OGTT with venous blood sampling may not be feasible in the screening phase preceding large epidemiological studies. We have conducted a population-based screening in 2715 men and women and evaluated the diagnostic validity of capillary plasma glucose concentration measurements versus venous plasma glucose concentration measurements in a subset of 350 subjects. METHODS: During a single OGTT, glucose concentrations were measured in venous plasma as well as in capillary plasma. RESULTS: Based on the 1999 WHO criteria for venous glucose concentrations, the study population (n=350) yielded 97 subjects with type 2 diabetes mellitus, 77 subjects with impaired glucose tolerance and 176 subjects with normal glucose tolerance. Sensitivity and specificity to diagnose type 2 diabetes mellitus by capillary plasma were 84% and 98%, respectively. Consistent classification by either venous or capillary plasma glucose measurements was 78% (kappa=0.65, p<0.001). CONCLUSION: Capillary glucose measurements are suitable for use in epidemiological studies to diagnose and detect type 2 diabetes and normal glucose tolerance. Use of capillary measurements can result in cost-effective inclusion schemes in epidemiological studies.

Aged↗

PubMed2003

Study on lifestyle-intervention and impaired glucose tolerance Maastricht (SLIM): design and screening results.

The study on lifestyle-intervention and impaired glucose tolerance Maastricht (SLIM) is a 3 years randomised clinical trial designed to evaluate the effect of a combined diet and physical activity intervention program on glucose tolerance in a Dutch population at increased risk for developing type 2 diabetes. Here the design of the lifestyle-intervention study is described and results are presented from the preliminary population screening, conducted between March 1999 and June 2000. In total, 2,820 subjects with an increased risk of having disturbances in glucose homeostasis (i.e. age >40 years and BMI>25 kg/m(2) or a family history of diabetes) underwent a first oral glucose tolerance test (OGTT). Abnormal glucose homeostasis was detected in 826 subjects (30.4%): 226 type 2 diabetes (type 2DM, 8.3%), 215 impaired fasting glucose (IFG, 7.9%) and 385 impaired glucose tolerance (IGT, 14.2%). Both increasing age and BMI were strongly related to the prevalence of IGT and diabetes. After a second OGTT, 114 subjects with glucose intolerance and in otherwise good health were eligible for participation in the intervention study (SLIM). The high prevalence of disturbances in glucose homeostasis observed in the preliminary screening underscore the importance of early (lifestyle) interventions in those at risk for developing diabetes. SLIM will address this topic in the Dutch population.

Blood Glucose↗

PubMed2003

Lifestyle intervention according to general recommendations improves glucose tolerance.

OBJECTIVE: Changing dietary and physical activity habits has the potential to postpone or prevent the development of type 2 diabetes. However, it needs to be assessed whether moderate interventions, in agreement with current guidelines for the general population, are effective. We evaluated the impact of a 2-year combined diet and physical activity intervention program on glucose tolerance in Dutch subjects at increased risk for developing diabetes. RESEARCH METHODS AND PROCEDURES: Subjects with glucose intolerance were randomly assigned to either the lifestyle intervention group (INT) or control group (CON). The INT received regular dietary advice and was stimulated to increase their physical activity. The CON received a brief leaflet about healthy diet and increased physical activity. Primary outcome measure was the change in glucose tolerance. RESULTS: In total, 88 subjects completed 2 years of intervention (40 subjects in the INT, 48 subjects in the CON, mean BMI 29.4 kg/m2). Subjects in the INT reduced their body weight, waist circumference, and (saturated) fat intake and improved their aerobic capacity. Two-hour plasma glucose concentration declined from 8.7 to 8.0 mM in the INT and rose from 8.6 to 9.4 mM in the CON (p < 0.01). Subjects adherent to both the diet and exercise intervention showed the largest reduction in 2-hour glucose levels. DISCUSSION: Our results showed that a lifestyle intervention program according to general recommendations improves glucose tolerance, even in a less obese and more physical active population. Furthermore, our results underscore the importance of combining diet and physical activity to improve glucose tolerance and insulin resistance.

Behavior Therapy↗

PubMed2002

Substrate oxidation, obesity and exercise training.

Regular physical exercise is of the utmost importance in the treatment of obesity because exercise is one of the factors determining long-term weight maintenance in weight reduction programmes and because exercise has been associated with a reduced risk for developing type 2 diabetes mellitus and cardiovascular disease. Obesity is associated with an impaired utilization of fat as a fuel during post-absorptive conditions, during beta-adrenergic stimulation and possibly during exercise, although the latter data are controversial. One of the underlying mechanisms for the positive effect of exercise training in obesity may be related to its effects on fat utilization because exercise training has been shown to increase basal fat oxidation and exercise fat oxidation in lean volunteers. Data on the effect of aerobic exercise training on exercise fat oxidation are controversial, whereas the available data indicate that exercise training may not be able to increase resting fat oxidation or 24-hour fat oxidation in obese subjects. Because disturbed muscle fat oxidation may be a primary event in the aetiology of obesity it is of the utmost importance to obtain more information on how and whether exercise training may be able to compensate for these impairments.

Adipose Tissue↗

PubMed2002

The fate of [U-(13)C]palmitate extracted by skeletal muscle in subjects with type 2 diabetes and control subjects.

The current study investigated the fate of a [U-(13)C]palmitate tracer extracted by forearm muscle in type 2 diabetic and control subjects. We studied seven healthy lean male subjects and seven obese male subjects with type 2 diabetes using the forearm muscle balance technique with continuous intravenous infusion of the stable isotope tracer [U-(13)C]palmitate under baseline conditions and during intravenous infusion of the nonselective beta-agonist isoprenaline (ISO; 20 ng *kg(-1) lean body mass* min(-1)). In skeletal muscle of control subjects, there was a significant release of (13)C-labeled oxidation products in the form of (13)CO(2) (15% of (13)C uptake from labeled palmitate) and a significant release of (13)C-labeled glutamine (release of (13)C-labeled atoms from glutamine was 6% of (13)C uptake from labeled palmitate), whereas in type 2 diabetic subjects there was no detectable release of (13)CO(2) and (13)C-glutamine, despite a significant uptake of [U-(13)C]palmitate (60% of control value). There was net uptake of arterial (13)C-labeled glutamate by forearm muscle in both groups. Also, the ISO-induced increase in arterial glutamine enrichment and arterial concentration of (13)C-glutamine was more pronounced in the diabetic group relative to control subjects. In view of the diminished ISO-induced release of (13)C-glutamine from type 2 diabetic muscle, the latter data indicate that more [U-(13)C]palmitate entered the liver in the diabetic group and was incorporated into newly synthesized glutamine and glutamate molecules. Thus, the lack of release of (13)C-labeled oxidation products by type 2 diabetic muscle during beta-adrenergic stimulation, despite significant [U-(13)C]palmitate uptake, indicates differences in the handling of fatty acids between type 2 diabetic subjects and healthy control subjects.

Adrenergic beta-Agonists↗