👤 Edwin C M Mariman

Energy restriction induces adaptations in resting energy expenditure (REE) and physical activity; inter-individual variability could be ascribed to genetic predisposition.The aim was to examine if changes in REE and physical activity as a result of weight loss were affected by candidate single nucleotide polymorphisms (SNPs). 148 subjects (39 men, 109 women), mean ± SD age: 41 ± 9 year; body mass index (BMI): 31.9 ± 3.0 kg/m The heterozygotic genotype of Carrying the minor Show less

Energy restriction induces adaptations in resting energy expenditure (REE) and physical activity; inter-individual variability could be ascribed to genetic predisposition. The aim was to examine if changes in REE and physical activity as a result of weight loss were affected by candidate single nucleotide polymorphisms (SNPs). 148 subjects (39 men, 109 women), mean ± SD age: 41 ± 9 year; body mass index (BMI): 31.9 ± 3.0 kg/m The heterozygotic genotype of FTO was associated with a higher amount of physical activity (1.71 Mcounts/d; CI 1.62-1.81) compared to the homozygotic major genotype (1.50 Mcounts/d; CI 1.40-1.59) (P < 0.001) while the homozygotic risk allele genotype was not different (1.56 Mcounts/d; CI 1.39-1.74) at baseline; moreover, a similar pattern was observed after energy restriction. Carrying the homozygotic minor genotype of ADRB2 was associated with a larger decrease in REE (P < 0.05) and greater adaptive thermogenesis (P < 0.05) after weight loss. Carrying the minor ADRB2 allele homozygous was associated with a larger diet induced metabolic adaptation in energy expenditure and suggest a central role for reduced lipid mobilization. Carrying the risk allele of FTO homozygous was not associated with lower physical activity at baseline or after weight loss. Heterozygous carriers of one FTO risk allele showed greater physical activity before and after weight loss which might protect them in part from the higher obesity risk associated with FTO. Show less

Angiopoietin-like protein 4 (ANGPTL4) plays a role in lipid partitioning by inhibiting lipoprotein lipase (LPL)-dependent plasma clearance of triacylglycerol in adipose tissue. We investigated the effects of diet-induced weight loss on plasma ANGPTL4 concentrations in relation to in vivo adipose tissue LPL activity and lipolysis and adipose tissue ANGPTL4 release in overweight/obese participants. Sixteen individuals (BMI: 28-35 kg/m Show less

Primary cilia are organelles that are present on many different cell types, either transiently or permanently. They play a crucial role in receiving signals from the environment and passing these signals to other parts of the cell. In that way, they are involved in diverse processes such as adipocyte differentiation and olfactory sensation. Mutations in genes coding for ciliary proteins often have pleiotropic effects and lead to clinical conditions, ciliopathies, with multiple symptoms. In this study, we reviewed observations from ciliopathies with obesity as one of the symptoms. It shows that variation in cilia-related genes is itself not a major cause of obesity in the population but may be a part of the multifactorial aetiology of this complex condition. Both common polymorphisms and rare deleterious variants may contribute to the obesity risk. Genotype-phenotype relationships have been noticed. Among the ciliary genes, obesity differs with regard to severity and age of onset, which may relate to the influence of each gene on the balance between pro- and anti-adipogenic processes. Analysis of the function and location of the proteins encoded by these ciliary genes suggests that obesity is more linked to activities at the basal area of the cilium, including initiation of the intraflagellar transport, but less to the intraflagellar transport itself. Regarding the role of cilia, three possible mechanistic processes underlying obesity are described: adipogenesis, neuronal food intake regulation and food odour perception. Show less

Proteomic technologies applied for profiling human biofluids and blood cells are considered to reveal new biomarkers of exposure or provide insights into novel mechanisms of adaptation. Both a non-targeted (classical 2D-electrophoresis combined with mass spectrometry) as well as a targeted proteomic approach (multiplex immunoassay) were applied to investigate how fasting for 36 h, as compared to 12 h, affects the proteome of platelets, peripheral blood mononuclear cells (PBMC), plasma, urine and saliva collected from ten healthy volunteers. Between-subject variability was highest in the plasma proteome and lowest in the PBMC proteome. Random Forests analysis performed on the entire dataset revealed that changes in the level of the RhoGDI2 protein in PBMC and plasma ApoA4 levels were the two most obvious biomarkers of an extended fasting. Random Forests (RF) analysis of the multiplex immunoassay data revealed leptin and MMP-3 as biomarkers for extended fasting. However, high between-subject variability may have masked the extended fasting effects in the proteome of the biofluids and blood cells. Identification of significantly changed proteins in biofluids and blood cells using a non-targeted approach, together with the outcome of targeted analysis revealed both known and novel markers for a 36 h fasting period, including the cellular proteins RhoGDI2 and CLIC1, and plasma proteins ApoA4, leptin and MMP-3. The PBMC proteome exhibited the lowest between-subject variability and therefore these cells appear to represent the best biosamples for biomarker discovery in human nutrigenomics. Show less

Nonparametric approaches have been developed that are able to analyze large numbers of single nucleotide polymorphisms (SNPs) in modest sample sizes. These approaches have different selection features and may not provide similar results when applied to the same dataset. Therefore, we compared the results of three approaches (set association, random forests and multifactor dimensionality reduction [MDR]) to select from a total of 93 candidate SNPs a subset of SNPs that are important in determining high-density lipoprotein (HDL)-cholesterol levels. The study population consisted of a random sample from a Dutch monitoring project for cardiovascular disease risk factors and was dichotomized into cases (low HDL-cholesterol, n = 533) and non-cases (high HDL-cholesterol, n = 545) based on gender-specific median values for HDL cholesterol. Clearly, all three approaches prioritized three SNPs as important (CETP Taq1B, CETP-629 C/A and LPL Ser447X). Two SNPs with weaker main effects were additionally prioritized by random forests (APOC3 3175 G/C and CCR2 Val62Ile), whereas MTHFR 677 C/T was selected in combination with CETP Taq1B as best model by MDR. Obtained p-values for the selected models were significant for the set association approach (p =.0019), random forests (p<.01) and MDR (p<.02). In conclusion, the application of a combination of multi-locus methods is a useful approach in genetic association studies to select a well-defined set of important SNPs for further statistical and epidemiological interpretation, providing increased confidence and more information compared with the application of only one method. Show less