Edwin Mariman - Academia.edu (original) (raw)

Papers by Edwin Mariman

Research paper thumbnail of Paternal Exposure to Environmental Chemical Stress Affects Male Offspring's Hepatic Mitochondria

Toxicological sciences : an official journal of the Society of Toxicology, 2018

Preconceptional paternal exposures may affect offspring's health, which cannot be explained b... more Preconceptional paternal exposures may affect offspring's health, which cannot be explained by mutations in germ cells, but by persistent changes in the regulation of gene expression. Therefore, we investigated whether pre-conceptional paternal exposure to benzo[a]pyrene (B[a]P) could alter the offspring's phenotype. Male C57BL/6 mice were exposed to B[a]P by gavage for 6 weeks, 3× per week, and were crossed with unexposed BALB-c females 6 weeks after the final exposure. The offspring was kept under normal feeding conditions and was sacrificed at 3 weeks of age. Analysis of the liver proteome by 2D-gel electrophoresis and mass spectrometry indicated that proteins involved in mitochondrial function were significantly downregulated in the offspring of exposed fathers. This down-regulation of mitochondrial proteins was paralleled by a reduction in mitochondrial DNA copy number and reduced activity of citrate synthase and β-hydroxyacyl-CoA dehydrogenase, but in male offspring on...

Research paper thumbnail of Combined Analysis of Stress- and ECM-Related Genes in Their Effect on Weight Regain

Obesity (Silver Spring, Md.), 2018

During weight loss, the volume of adipocytes decreases, leading to stress because of the misfit b... more During weight loss, the volume of adipocytes decreases, leading to stress because of the misfit between the cell contents and the surrounding extracellular matrix (ECM). This stress can be resolved by remodeling the ECM or the restorage of triglycerides within the adipocytes. The objective of this study was to investigate the existence of a connection between stress-related and ECM-related genes that is associated with weight regain. Thirty-one participants with overweight or obesity followed a 5-week very-low-calorie diet (500 kcal/d) with a subsequent 4-week weight-stable diet (WS), and then an uncontrolled 9-month follow-up. Adipose tissue biopsies were collected for microarray analysis. A correlation and interaction analysis was performed with the weight regain percentage (WR%) ([weight after follow-up - weight after WS] ÷ weight after WS × 100%) by using two gene sets that were previously defined as "stress-related" (n = 107) and "ECM-related" genes (n = 277...

Research paper thumbnail of A role for leukocyte integrins and extracellular matrix remodeling of adipose tissue in the risk of weight regain after weight loss

The American journal of clinical nutrition, 2017

Background: Weight loss (WL) is often followed by weight regain after an energy-restricted dietar... more Background: Weight loss (WL) is often followed by weight regain after an energy-restricted dietary intervention (DI). When people are following a diet, the volume of an adipocyte decreases by loss of triglycerides, which creates stress between the cell contents and the surrounding extracellular matrix (ECM). Previously, we observed that genetic variations in ECM genes are associated with an increased risk of weight regain.Objective: We investigated the relation between the expression of ECM genes during WL and a period of weight stabilization (WS) and the risk of weight regain.Design: In this randomized controlled trial, 61 healthy overweight or obese participants followed either a 5-wk very-low-calorie diet (VLCD; 500 kcal/d) or a 12-wk low-calorie diet (1250 kcal/d) (WL period) with a subsequent 4-wk WS period and a 9-mo follow-up. The WL and WS periods combined were considered the DI. Abdominal subcutaneous adipose tissue biopsy samples were collected for microarray analysis. Gen...

Research paper thumbnail of Adipose Tissue Meal-Derived Fatty Acid Uptake Before and After Diet-Induced Weight Loss in Adults with Overweight and Obesity

Obesity (Silver Spring, Md.), 2017

This study investigated whether diet-induced weight loss alters indices of in vivo postprandial f... more This study investigated whether diet-induced weight loss alters indices of in vivo postprandial fat uptake in adipose tissue (AT) and whether these changes are associated with weight regain in adults with overweight and obesity. In this randomized controlled trial, 16 (6 male) individuals (BMI: 28-35 kg/m(2) ) were randomized to either a low-calorie diet (1,250 kcal/d) for 12 weeks or a very-low-calorie diet (500 kcal/d) for 5 weeks (weight loss [WL] period) followed by a 4-week weight-stable (WS) period (together, the dietary intervention [DI] period) and a 9-month follow-up period. Arteriovenous difference measurements combined with stable isotope labeling ([U-(13) C] palmitate) of a mixed meal were used to determine postprandial fatty acid uptake in AT. Body weight was significantly reduced during the WL period (-8.2 ± 0.6 kg, P < 0.001), remained stable during the WS period (0.4 ± 0.3 kg, P = 0.150), and increased during follow-up (3.5 ± 0.8 kg, P = 0.001). Meal-derived in vi...

Research paper thumbnail of The cilium: a cellular antenna with an influence on obesity risk

The British journal of nutrition, Jan 20, 2016

Primary cilia are organelles that are present on many different cell types, either transiently or... more 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, wh...

Research paper thumbnail of Weight loss-induced stress in subcutaneous adipose tissue is related to weight regain

British Journal of Nutrition, 2016

Initial successful weight loss is often followed by weight regain after the dietary intervention.... more Initial successful weight loss is often followed by weight regain after the dietary intervention. Compared with lean people, cellular stress in adipose tissue is increased in obese subjects. However, the relation between cellular stress and the risk for weight regain after weight loss is unclear. Therefore, we determined the expression levels of stress proteins during weight loss and weight maintenance in relation to weight regain.In vivofindings were compared with results fromin vitrocultured human Simpson–Golabi–Behmel syndrome (SGBS) adipocytes. In total, eighteen healthy subjects underwent an 8-week diet programme with a 10-month follow-up. Participants were categorised as weight maintainers or weight regainers (WR) depending on their weight changes during the intervention. Abdominal subcutaneous adipose tissue biopsies were obtained before and after the diet and after the follow-up.In vitrodifferentiated SGBS adipocytes were starved for 96 h with low (0·55 mm) glucose. Levels o...

Research paper thumbnail of Variation in extracellular matrix genes is associated with weight regain after weight loss in a sex-specific manner

Genes & nutrition, 2015

The extracellular matrix (ECM) of adipocytes is important for body weight regulation. Here, we in... more The extracellular matrix (ECM) of adipocytes is important for body weight regulation. Here, we investigated whether genetic variation in ECM-related genes is associated with weight regain among participants of the European DiOGenes study. Overweight and obese subjects (n = 469, 310 females, 159 males) were on an 8-week low-calorie diet with a 6-month follow-up. Body weight was measured before and after the diet, and after follow-up. Weight maintenance scores (WMS, regained weight as percentage of lost weight) were calculated based on the weight data. Genotype data were retrieved for 2903 SNPs corresponding to 124 ECM-related genes. Regression analyses provided us with six significant SNPs associated with the WMS in males: 3 SNPs in the POSTN gene and a SNP in the LAMB1, COL23A1, and FBLN5 genes. For females, 1 SNP was found in the FN1 gene. The risk of weight regain was increased by: the C/C genotype for POSTN in a co-dominant model (OR 8.25, 95 % CI 2.85-23.88) and the T/C-C/C geno...

Research paper thumbnail of Extreme obesity is associated with variation in genes related to the circadian rhythm of food intake and hypothalamic signaling

Physiological genomics, Jan 24, 2015

The hypothalamus is important for regulation of energy intake. Mutations in genes involved in the... more The hypothalamus is important for regulation of energy intake. Mutations in genes involved in the function of the hypothalamus can lead to early-onset severe obesity. To look further into this, we have followed a strategy that allowed us to identify rare and common gene variants as candidates for the background of extreme obesity from a relatively small cohort. For that we focused on subjects with a well-selected phenotype and on a defined gene set, and used a rich source of genetic data with stringent cut-off values. A list of 166 genes functionally related to the hypothalamus was generated. In those genes complete exome sequence data from 30 extreme obese subjects (60 genomes) were screened for novel rare indel, nonsense and missense variants with a predicted negative impact on protein function. In addition, (moderately) common variants in those genes were analyzed for allelic association using the general population as reference (FDR<0.05). Six novel rare deleterious missense ...

Research paper thumbnail of An adipobiological model for weight regain after weight loss

Adipobiology, 2011

within one year, regain of a considerable amount of the weight lost by calorie restriction is a c... more within one year, regain of a considerable amount of the weight lost by calorie restriction is a common phenomenon for up to 80% of individuals. This has been mainly attributed to psychosocial and behavioral influences. However, our recent findings point to a potential involvement of adipocytes in the risk for weight regain. During weight loss adipocytes build up resistance against releasing more fat, which is demonstrated by the differential expression of markers for cellular stress. This stress may be based on mechanical forces that arise between the shrinking cell and the surrounding rigid basal lamina. For adipocytes the best way to alleviate this stress is by returning to their original volume, which can be achieved by re-storage of triglycerides. To ascertain a sufficient supply of glucose and fat for re-storage, adipocytes change their pattern of secreted adipokines altering the total body metabolism and promoting energy intake. As a consequence the host will regain weight. Further research is needed to prove this model. if the model receives further support, the existence of an adipocytes-based autonomous cause for weight regain may be taken as an excuse to abandon measures needed to maintain the reduced weight. Therefore, care must be taken in the presentation of this model to the public. On the other hand, the model will also provide novel ways for prevention of weight regain.

Research paper thumbnail of High frequency of rare variants with a moderate-to-high predicted biological effect in protocadherin genes of extremely obese

Genes & nutrition, 2014

Relatively rare variants with a moderate-to-high biological effect may contribute to the genetic ... more Relatively rare variants with a moderate-to-high biological effect may contribute to the genetic predisposition of common disorders. To investigate this for obesity, we performed exome sequencing for 30 young (mean age: 29.7 years) extremely obese Caucasian subjects (mean body mass index: 51.1 kg/m(2); m/f = 11/29). Rare variants with a moderate-to-high predicted biological effect were assembled and subjected to functional clustering analysis. It showed that the 55 clustered protocadherin genes on chromosome 5q31 have a significantly (P = 0.002) higher frequency of rare variants than a set of 325 reference genes. Since the protocadherin genes are expressed in the hypothalamus, we tested another 167 genes related to the function of the hypothalamus, but in those genes, the frequency of rare variants was not different from that of the reference genes. To verify the relation of variation in the protocadherin genes with extreme obesity, we analyzed data from more than 4,000 European Ame...

Research paper thumbnail of Blood profiling of proteins and steroids during weight maintenance with manipulation of dietary protein level and glycaemic index

British Journal of Nutrition, 2012

Weight regain after weight loss is common. In the Diogenes dietary intervention study, a high-pro... more Weight regain after weight loss is common. In the Diogenes dietary intervention study, a high-protein and low-glycaemic index (GI) diet improved weight maintenance. The objective of the present study was to identify (1) blood profiles associated with continued weight loss and weight regain (2) blood biomarkers of dietary protein and GI levels during the weight-maintenance phase. Blood samples were collected at baseline, after 8 weeks of low-energy diet-induced weight loss and after a 6-month dietary intervention period from female continued weight losers (n 48) and weight regainers (n 48), evenly selected from four dietary groups that varied in protein and GI levels. The blood concentrations of twenty-nine proteins and three steroid hormones were measured. The changes in analytes during weight maintenance largely correlated negatively with the changes during weight loss, with some differences between continued weight losers and weight regainers. Increases in leptin (LEP) and C-reactive protein (CRP) were significantly associated with weight regain (P,0•001 and P¼ 0•005, respectively), and these relationships were influenced by the diet. Consuming a high-protein and high-GI diet dissociated the positive relationship between the change in LEP concentration and weight regain. CRP increased during the weight-maintenance period only in weight regainers with a high-protein diet (P, 0•001). In addition, testosterone, luteinising hormone, angiotensinogen, plasminogen activator inhibitor-1, resistin, retinol-binding protein 4, insulin, glucagon, haptoglobin and growth hormone were also affected by the dietary intervention. The blood profile reflects not only the weight change during the maintenance period, but also the macronutrient composition of the dietary intervention, especially the protein level.

Research paper thumbnail of Plasma pigment epithelium-derived factor is positively associated with obesity in Caucasian subjects, in particular with the visceral fat depot

European Journal of …, 2008

Objective: Adipose tissue releases factors (adipokines) that influence local, peripheral as well ... more Objective: Adipose tissue releases factors (adipokines) that influence local, peripheral as well as central processes. In the present study, we determined the relationship between plasma concentration of a recently identified adipokine, pigment epithelium-derived factor (SERPINF1), and human obesity, particularly specific adipose tissue depots, and other features of the metabolic syndrome. Methods: We examined the plasma concentration of SERPINF1, anthropometric parameters, abdominal s.c. and visceral adipose tissue, lipid, glucose, insulin, and alanine aminotransferase level in a non-diabetic general Caucasian population (nZ59). Results: Plasma SERPINF1 level in males (6.2G2.1 mg/ml) was higher than in females (3.1G 1.4 mg/ml; P!0.001). Plasma SERPINF1 was positively correlated with age and all features of metabolic syndrome. However, in multiple linear regression analysis with adjustment for age and gender, only visceral fat thickness (bZ0.361, PZ0.010) and body mass index (bZ0.288, PZ0.008) were significant independent determinants of plasma SERPINF1 level, together with gender (bZK0.424, P!0.001). Conclusions: We conclude that the plasma SERPINF1 level is strongly associated with body adiposity, in particular with the visceral fat depot in the non-diabetic general population. This association may (partly) explain the relationship between SERPINF1 and metabolic syndrome in this population.

Research paper thumbnail of Comparative proteomic analysis of cell lines and scrapings of the human intestinal epithelium

BMC …, 2007

In vitro models are indispensable study objects in the fields of cell and molecular biology, with... more In vitro models are indispensable study objects in the fields of cell and molecular biology, with advantages such as accessibility, homogeneity of the cell population, reproducibility, and growth rate. The Caco-2 cell line, originating from a colon carcinoma, is a widely used in vitro ...

Research paper thumbnail of The circulating PBEF/NAMPT/visfatin level is associated with a beneficial blood lipid profile

… European Journal of …, 2007

Adipose tissue is an endocrine organ capable of secreting a number of adipokines with a role in t... more Adipose tissue is an endocrine organ capable of secreting a number of adipokines with a role in the regulation of adipose tissue and whole-body metabolism. We used twodimensional gel electrophoresis combined with mass spectrometry to profile the secreted proteins from (pre)adipocytes. The culture medium of 3T3-L1 cells during adipocyte differentiation was screened, and 41 proteins that responded to blocking of secretion by 20°C treatment and/or brefeldin A treatment were identified. Prohibitin, stress-70 protein, and adhesion-regulating molecule 1 are reported for the first time as secreted proteins. In addition, procollagen C-proteinase enhancer protein, galectin-1, cyclophilin A and C, and SF20/IL-25 are newly identified as adipocyte secreted factors. Secretion profiles indicated a dynamic environment including an actively remodeling extracellular matrix and several factors involved in growth regulation.

Research paper thumbnail of Postprandial responses in hunger and satiety are associated with the rs9939609 single nucleotide polymorphism in FTO

American Journal of Clinical Nutrition, 2009

Background: The common rs9939609 single nucleotide polymorphism (SNP) in the fat mass and obesity... more Background: The common rs9939609 single nucleotide polymorphism (SNP) in the fat mass and obesity-associated (FTO) gene is associated with adiposity, possibly by affecting satiety responsiveness. Objective: The objective was to determine whether postprandial responses in hunger and satiety are associated with rs9939609, taking interactions with other relevant candidate genes into account. Design: Sixty-two women and 41 men [age: 31 6 14 y; body mass index (in kg/m 2): 25.0 6 3.1] were genotyped for 5 SNPs in FTO, DNMT1, DNMT3B, LEP, and LEPR. Individuals received fixed meals provided in energy balance. Hunger and satiety were determined pre-and postprandially by using visual analog scales. Results: A general association test showed a significant association between postprandial responses in hunger and satiety with rs9939609 (P = 0.036 and P = 0.050, respectively). Individuals with low postprandial responses in hunger and satiety were overrepresented among TA/AA carriers in rs9939609 (FTO) compared with TT carriers (dominant and additive model: P = 0.013 and P = 0.020, respectively). Moreover, multifactor dimensionality reduction showed significant epistatic interactions for the postprandial decrease in hunger involving rs9939609 (FTO), rs992472 (DNMT3B), and rs1137101 (LEPR). Individuals with a low postprandial decrease in hunger were overrepresented among TA/AA (dominant), CC/CA (recessive), and AG/GG (dominant) carriers in rs9939609 (FTO), rs992472 (DNMT3B), and rs1137101 (LEPR), respectively (n = 39), compared with TT, AA, and/or AA carriers in these SNPs, respectively (P = 0.00001). Each SNP had an additional effect. Conclusions: Our results confirm a role for FTO in responsiveness to hunger and satiety cues in adults in an experimental setting. The epistatic interaction suggests that DNA methylation, an epigenetic process, affects appetite.

Research paper thumbnail of Expression of Genes Involved in Lipid Metabolism in Men with Impaired Glucose Tolerance: Impact of Insulin Stimulation and Weight Loss

Journal of Nutrigenetics and Nutrigenomics, 2010

Background:The impaired glucose tolerance (IGT) state is characterized by insulin resistance. Dis... more Background:The impaired glucose tolerance (IGT) state is characterized by insulin resistance. Disturbances in fatty acid (FA) metabolism may underlie this reduced insulin sensitivity. The aim of this study was to investigate whether the prediabetic state is accompanied by changes in the expression of genes involved in FA handling during fasting and in insulin-mediated conditions and to study the impact of

Research paper thumbnail of High fat diet-induced changes in mouse muscle mitochondrial phospholipids do not impair mitochondrial respiration despite insulin resistance

Background: Type 2 diabetes mellitus and muscle insulin resistance have been associated with redu... more Background: Type 2 diabetes mellitus and muscle insulin resistance have been associated with reduced capacity of skeletal muscle mitochondria, possibly as a result of increased intake of dietary fat. Here, we examined the hypothesis that a prolonged high-fat diet consumption (HFD) increases the saturation of muscle mitochondrial membrane phospholipids causing impaired mitochondrial oxidative capacity and possibly insulin resistance. Methodology: C57BL/6J mice were fed an 8-week or 20-week low fat diet (10 kcal%; LFD) or HFD (45 kcal%). Skeletal muscle mitochondria were isolated and fatty acid (FA) composition of skeletal muscle mitochondrial phospholipids was analyzed by thin-layer chromatography followed by GC. High-resolution respirometry was used to assess oxidation of pyruvate and fatty acids by mitochondria. Insulin sensitivity was estimated by HOMA-IR.

Research paper thumbnail of Genetic associations with acute stress-related changes in eating in the absence of hunger

Patient Education and Counseling, 2010

BackgroundAcute psychological stress is associated with eating in the absence of hunger.

Research paper thumbnail of Leptin-adiposity relationship changes, plus behavioral and parental factors, are involved in the development of body weight in a Dutch children cohort

Physiology & behavior, Jan 18, 2008

The development of body weight is determined by different factors, namely genetic, behavioral, pa... more The development of body weight is determined by different factors, namely genetic, behavioral, parental and physiological. To investigate whether genetic, behavioral, parental and physiological factors are involved and the extent of involvement in the development of body weight at ages 12 and 13 y in a Dutch children cohort. In a Dutch cohort of 94 children at ages 12 and 13 y, we determined anthropometric measurements, body composition, leptin concentrations, TFEQ scores, physical activity, as well as 3 polymorphisms, and in the parents we determined anthropometric measurements and TFEQ scores. 11% of the children in the cohort were classified as overweight. The genotype frequency distributions of the PPARy2, GRL and CNTF genes at ages 12 and 13 y were not significantly different for the overweight children compared to the lean children. Overweight children showed higher dietary restraint and disinhibition scores. Overweight children's parents had a higher BMI, dietary restrain...

Research paper thumbnail of The challenge for genetic epidemiologists: how to analyze large numbers of SNPs in relation to complex diseases

BMC genetics, 2006

Genetic epidemiologists have taken the challenge to identify genetic polymorphisms involved in th... more Genetic epidemiologists have taken the challenge to identify genetic polymorphisms involved in the development of diseases. Many have collected data on large numbers of genetic markers but are not familiar with available methods to assess their association with complex diseases. Statistical methods have been developed for analyzing the relation between large numbers of genetic and environmental predictors to disease or disease-related variables in genetic association studies. In this commentary we discuss logistic regression analysis, neural networks, including the parameter decreasing method (PDM) and genetic programming optimized neural networks (GPNN) and several non-parametric methods, which include the set association approach, combinatorial partitioning method (CPM), restricted partitioning method (RPM), multifactor dimensionality reduction (MDR) method and the random forests approach. The relative strengths and weaknesses of these methods are highlighted. Logistic regression ...

Research paper thumbnail of Paternal Exposure to Environmental Chemical Stress Affects Male Offspring's Hepatic Mitochondria

Toxicological sciences : an official journal of the Society of Toxicology, 2018

Preconceptional paternal exposures may affect offspring's health, which cannot be explained b... more Preconceptional paternal exposures may affect offspring's health, which cannot be explained by mutations in germ cells, but by persistent changes in the regulation of gene expression. Therefore, we investigated whether pre-conceptional paternal exposure to benzo[a]pyrene (B[a]P) could alter the offspring's phenotype. Male C57BL/6 mice were exposed to B[a]P by gavage for 6 weeks, 3× per week, and were crossed with unexposed BALB-c females 6 weeks after the final exposure. The offspring was kept under normal feeding conditions and was sacrificed at 3 weeks of age. Analysis of the liver proteome by 2D-gel electrophoresis and mass spectrometry indicated that proteins involved in mitochondrial function were significantly downregulated in the offspring of exposed fathers. This down-regulation of mitochondrial proteins was paralleled by a reduction in mitochondrial DNA copy number and reduced activity of citrate synthase and β-hydroxyacyl-CoA dehydrogenase, but in male offspring on...

Research paper thumbnail of Combined Analysis of Stress- and ECM-Related Genes in Their Effect on Weight Regain

Obesity (Silver Spring, Md.), 2018

During weight loss, the volume of adipocytes decreases, leading to stress because of the misfit b... more During weight loss, the volume of adipocytes decreases, leading to stress because of the misfit between the cell contents and the surrounding extracellular matrix (ECM). This stress can be resolved by remodeling the ECM or the restorage of triglycerides within the adipocytes. The objective of this study was to investigate the existence of a connection between stress-related and ECM-related genes that is associated with weight regain. Thirty-one participants with overweight or obesity followed a 5-week very-low-calorie diet (500 kcal/d) with a subsequent 4-week weight-stable diet (WS), and then an uncontrolled 9-month follow-up. Adipose tissue biopsies were collected for microarray analysis. A correlation and interaction analysis was performed with the weight regain percentage (WR%) ([weight after follow-up - weight after WS] ÷ weight after WS × 100%) by using two gene sets that were previously defined as "stress-related" (n = 107) and "ECM-related" genes (n = 277...

Research paper thumbnail of A role for leukocyte integrins and extracellular matrix remodeling of adipose tissue in the risk of weight regain after weight loss

The American journal of clinical nutrition, 2017

Background: Weight loss (WL) is often followed by weight regain after an energy-restricted dietar... more Background: Weight loss (WL) is often followed by weight regain after an energy-restricted dietary intervention (DI). When people are following a diet, the volume of an adipocyte decreases by loss of triglycerides, which creates stress between the cell contents and the surrounding extracellular matrix (ECM). Previously, we observed that genetic variations in ECM genes are associated with an increased risk of weight regain.Objective: We investigated the relation between the expression of ECM genes during WL and a period of weight stabilization (WS) and the risk of weight regain.Design: In this randomized controlled trial, 61 healthy overweight or obese participants followed either a 5-wk very-low-calorie diet (VLCD; 500 kcal/d) or a 12-wk low-calorie diet (1250 kcal/d) (WL period) with a subsequent 4-wk WS period and a 9-mo follow-up. The WL and WS periods combined were considered the DI. Abdominal subcutaneous adipose tissue biopsy samples were collected for microarray analysis. Gen...

Research paper thumbnail of Adipose Tissue Meal-Derived Fatty Acid Uptake Before and After Diet-Induced Weight Loss in Adults with Overweight and Obesity

Obesity (Silver Spring, Md.), 2017

This study investigated whether diet-induced weight loss alters indices of in vivo postprandial f... more This study investigated whether diet-induced weight loss alters indices of in vivo postprandial fat uptake in adipose tissue (AT) and whether these changes are associated with weight regain in adults with overweight and obesity. In this randomized controlled trial, 16 (6 male) individuals (BMI: 28-35 kg/m(2) ) were randomized to either a low-calorie diet (1,250 kcal/d) for 12 weeks or a very-low-calorie diet (500 kcal/d) for 5 weeks (weight loss [WL] period) followed by a 4-week weight-stable (WS) period (together, the dietary intervention [DI] period) and a 9-month follow-up period. Arteriovenous difference measurements combined with stable isotope labeling ([U-(13) C] palmitate) of a mixed meal were used to determine postprandial fatty acid uptake in AT. Body weight was significantly reduced during the WL period (-8.2 ± 0.6 kg, P < 0.001), remained stable during the WS period (0.4 ± 0.3 kg, P = 0.150), and increased during follow-up (3.5 ± 0.8 kg, P = 0.001). Meal-derived in vi...

Research paper thumbnail of The cilium: a cellular antenna with an influence on obesity risk

The British journal of nutrition, Jan 20, 2016

Primary cilia are organelles that are present on many different cell types, either transiently or... more 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, wh...

Research paper thumbnail of Weight loss-induced stress in subcutaneous adipose tissue is related to weight regain

British Journal of Nutrition, 2016

Initial successful weight loss is often followed by weight regain after the dietary intervention.... more Initial successful weight loss is often followed by weight regain after the dietary intervention. Compared with lean people, cellular stress in adipose tissue is increased in obese subjects. However, the relation between cellular stress and the risk for weight regain after weight loss is unclear. Therefore, we determined the expression levels of stress proteins during weight loss and weight maintenance in relation to weight regain.In vivofindings were compared with results fromin vitrocultured human Simpson–Golabi–Behmel syndrome (SGBS) adipocytes. In total, eighteen healthy subjects underwent an 8-week diet programme with a 10-month follow-up. Participants were categorised as weight maintainers or weight regainers (WR) depending on their weight changes during the intervention. Abdominal subcutaneous adipose tissue biopsies were obtained before and after the diet and after the follow-up.In vitrodifferentiated SGBS adipocytes were starved for 96 h with low (0·55 mm) glucose. Levels o...

Research paper thumbnail of Variation in extracellular matrix genes is associated with weight regain after weight loss in a sex-specific manner

Genes & nutrition, 2015

The extracellular matrix (ECM) of adipocytes is important for body weight regulation. Here, we in... more The extracellular matrix (ECM) of adipocytes is important for body weight regulation. Here, we investigated whether genetic variation in ECM-related genes is associated with weight regain among participants of the European DiOGenes study. Overweight and obese subjects (n = 469, 310 females, 159 males) were on an 8-week low-calorie diet with a 6-month follow-up. Body weight was measured before and after the diet, and after follow-up. Weight maintenance scores (WMS, regained weight as percentage of lost weight) were calculated based on the weight data. Genotype data were retrieved for 2903 SNPs corresponding to 124 ECM-related genes. Regression analyses provided us with six significant SNPs associated with the WMS in males: 3 SNPs in the POSTN gene and a SNP in the LAMB1, COL23A1, and FBLN5 genes. For females, 1 SNP was found in the FN1 gene. The risk of weight regain was increased by: the C/C genotype for POSTN in a co-dominant model (OR 8.25, 95 % CI 2.85-23.88) and the T/C-C/C geno...

Research paper thumbnail of Extreme obesity is associated with variation in genes related to the circadian rhythm of food intake and hypothalamic signaling

Physiological genomics, Jan 24, 2015

The hypothalamus is important for regulation of energy intake. Mutations in genes involved in the... more The hypothalamus is important for regulation of energy intake. Mutations in genes involved in the function of the hypothalamus can lead to early-onset severe obesity. To look further into this, we have followed a strategy that allowed us to identify rare and common gene variants as candidates for the background of extreme obesity from a relatively small cohort. For that we focused on subjects with a well-selected phenotype and on a defined gene set, and used a rich source of genetic data with stringent cut-off values. A list of 166 genes functionally related to the hypothalamus was generated. In those genes complete exome sequence data from 30 extreme obese subjects (60 genomes) were screened for novel rare indel, nonsense and missense variants with a predicted negative impact on protein function. In addition, (moderately) common variants in those genes were analyzed for allelic association using the general population as reference (FDR<0.05). Six novel rare deleterious missense ...

Research paper thumbnail of An adipobiological model for weight regain after weight loss

Adipobiology, 2011

within one year, regain of a considerable amount of the weight lost by calorie restriction is a c... more within one year, regain of a considerable amount of the weight lost by calorie restriction is a common phenomenon for up to 80% of individuals. This has been mainly attributed to psychosocial and behavioral influences. However, our recent findings point to a potential involvement of adipocytes in the risk for weight regain. During weight loss adipocytes build up resistance against releasing more fat, which is demonstrated by the differential expression of markers for cellular stress. This stress may be based on mechanical forces that arise between the shrinking cell and the surrounding rigid basal lamina. For adipocytes the best way to alleviate this stress is by returning to their original volume, which can be achieved by re-storage of triglycerides. To ascertain a sufficient supply of glucose and fat for re-storage, adipocytes change their pattern of secreted adipokines altering the total body metabolism and promoting energy intake. As a consequence the host will regain weight. Further research is needed to prove this model. if the model receives further support, the existence of an adipocytes-based autonomous cause for weight regain may be taken as an excuse to abandon measures needed to maintain the reduced weight. Therefore, care must be taken in the presentation of this model to the public. On the other hand, the model will also provide novel ways for prevention of weight regain.

Research paper thumbnail of High frequency of rare variants with a moderate-to-high predicted biological effect in protocadherin genes of extremely obese

Genes & nutrition, 2014

Relatively rare variants with a moderate-to-high biological effect may contribute to the genetic ... more Relatively rare variants with a moderate-to-high biological effect may contribute to the genetic predisposition of common disorders. To investigate this for obesity, we performed exome sequencing for 30 young (mean age: 29.7 years) extremely obese Caucasian subjects (mean body mass index: 51.1 kg/m(2); m/f = 11/29). Rare variants with a moderate-to-high predicted biological effect were assembled and subjected to functional clustering analysis. It showed that the 55 clustered protocadherin genes on chromosome 5q31 have a significantly (P = 0.002) higher frequency of rare variants than a set of 325 reference genes. Since the protocadherin genes are expressed in the hypothalamus, we tested another 167 genes related to the function of the hypothalamus, but in those genes, the frequency of rare variants was not different from that of the reference genes. To verify the relation of variation in the protocadherin genes with extreme obesity, we analyzed data from more than 4,000 European Ame...

Research paper thumbnail of Blood profiling of proteins and steroids during weight maintenance with manipulation of dietary protein level and glycaemic index

British Journal of Nutrition, 2012

Weight regain after weight loss is common. In the Diogenes dietary intervention study, a high-pro... more Weight regain after weight loss is common. In the Diogenes dietary intervention study, a high-protein and low-glycaemic index (GI) diet improved weight maintenance. The objective of the present study was to identify (1) blood profiles associated with continued weight loss and weight regain (2) blood biomarkers of dietary protein and GI levels during the weight-maintenance phase. Blood samples were collected at baseline, after 8 weeks of low-energy diet-induced weight loss and after a 6-month dietary intervention period from female continued weight losers (n 48) and weight regainers (n 48), evenly selected from four dietary groups that varied in protein and GI levels. The blood concentrations of twenty-nine proteins and three steroid hormones were measured. The changes in analytes during weight maintenance largely correlated negatively with the changes during weight loss, with some differences between continued weight losers and weight regainers. Increases in leptin (LEP) and C-reactive protein (CRP) were significantly associated with weight regain (P,0•001 and P¼ 0•005, respectively), and these relationships were influenced by the diet. Consuming a high-protein and high-GI diet dissociated the positive relationship between the change in LEP concentration and weight regain. CRP increased during the weight-maintenance period only in weight regainers with a high-protein diet (P, 0•001). In addition, testosterone, luteinising hormone, angiotensinogen, plasminogen activator inhibitor-1, resistin, retinol-binding protein 4, insulin, glucagon, haptoglobin and growth hormone were also affected by the dietary intervention. The blood profile reflects not only the weight change during the maintenance period, but also the macronutrient composition of the dietary intervention, especially the protein level.

Research paper thumbnail of Plasma pigment epithelium-derived factor is positively associated with obesity in Caucasian subjects, in particular with the visceral fat depot

European Journal of …, 2008

Objective: Adipose tissue releases factors (adipokines) that influence local, peripheral as well ... more Objective: Adipose tissue releases factors (adipokines) that influence local, peripheral as well as central processes. In the present study, we determined the relationship between plasma concentration of a recently identified adipokine, pigment epithelium-derived factor (SERPINF1), and human obesity, particularly specific adipose tissue depots, and other features of the metabolic syndrome. Methods: We examined the plasma concentration of SERPINF1, anthropometric parameters, abdominal s.c. and visceral adipose tissue, lipid, glucose, insulin, and alanine aminotransferase level in a non-diabetic general Caucasian population (nZ59). Results: Plasma SERPINF1 level in males (6.2G2.1 mg/ml) was higher than in females (3.1G 1.4 mg/ml; P!0.001). Plasma SERPINF1 was positively correlated with age and all features of metabolic syndrome. However, in multiple linear regression analysis with adjustment for age and gender, only visceral fat thickness (bZ0.361, PZ0.010) and body mass index (bZ0.288, PZ0.008) were significant independent determinants of plasma SERPINF1 level, together with gender (bZK0.424, P!0.001). Conclusions: We conclude that the plasma SERPINF1 level is strongly associated with body adiposity, in particular with the visceral fat depot in the non-diabetic general population. This association may (partly) explain the relationship between SERPINF1 and metabolic syndrome in this population.

Research paper thumbnail of Comparative proteomic analysis of cell lines and scrapings of the human intestinal epithelium

BMC …, 2007

In vitro models are indispensable study objects in the fields of cell and molecular biology, with... more In vitro models are indispensable study objects in the fields of cell and molecular biology, with advantages such as accessibility, homogeneity of the cell population, reproducibility, and growth rate. The Caco-2 cell line, originating from a colon carcinoma, is a widely used in vitro ...

Research paper thumbnail of The circulating PBEF/NAMPT/visfatin level is associated with a beneficial blood lipid profile

… European Journal of …, 2007

Adipose tissue is an endocrine organ capable of secreting a number of adipokines with a role in t... more Adipose tissue is an endocrine organ capable of secreting a number of adipokines with a role in the regulation of adipose tissue and whole-body metabolism. We used twodimensional gel electrophoresis combined with mass spectrometry to profile the secreted proteins from (pre)adipocytes. The culture medium of 3T3-L1 cells during adipocyte differentiation was screened, and 41 proteins that responded to blocking of secretion by 20°C treatment and/or brefeldin A treatment were identified. Prohibitin, stress-70 protein, and adhesion-regulating molecule 1 are reported for the first time as secreted proteins. In addition, procollagen C-proteinase enhancer protein, galectin-1, cyclophilin A and C, and SF20/IL-25 are newly identified as adipocyte secreted factors. Secretion profiles indicated a dynamic environment including an actively remodeling extracellular matrix and several factors involved in growth regulation.

Research paper thumbnail of Postprandial responses in hunger and satiety are associated with the rs9939609 single nucleotide polymorphism in FTO

American Journal of Clinical Nutrition, 2009

Background: The common rs9939609 single nucleotide polymorphism (SNP) in the fat mass and obesity... more Background: The common rs9939609 single nucleotide polymorphism (SNP) in the fat mass and obesity-associated (FTO) gene is associated with adiposity, possibly by affecting satiety responsiveness. Objective: The objective was to determine whether postprandial responses in hunger and satiety are associated with rs9939609, taking interactions with other relevant candidate genes into account. Design: Sixty-two women and 41 men [age: 31 6 14 y; body mass index (in kg/m 2): 25.0 6 3.1] were genotyped for 5 SNPs in FTO, DNMT1, DNMT3B, LEP, and LEPR. Individuals received fixed meals provided in energy balance. Hunger and satiety were determined pre-and postprandially by using visual analog scales. Results: A general association test showed a significant association between postprandial responses in hunger and satiety with rs9939609 (P = 0.036 and P = 0.050, respectively). Individuals with low postprandial responses in hunger and satiety were overrepresented among TA/AA carriers in rs9939609 (FTO) compared with TT carriers (dominant and additive model: P = 0.013 and P = 0.020, respectively). Moreover, multifactor dimensionality reduction showed significant epistatic interactions for the postprandial decrease in hunger involving rs9939609 (FTO), rs992472 (DNMT3B), and rs1137101 (LEPR). Individuals with a low postprandial decrease in hunger were overrepresented among TA/AA (dominant), CC/CA (recessive), and AG/GG (dominant) carriers in rs9939609 (FTO), rs992472 (DNMT3B), and rs1137101 (LEPR), respectively (n = 39), compared with TT, AA, and/or AA carriers in these SNPs, respectively (P = 0.00001). Each SNP had an additional effect. Conclusions: Our results confirm a role for FTO in responsiveness to hunger and satiety cues in adults in an experimental setting. The epistatic interaction suggests that DNA methylation, an epigenetic process, affects appetite.

Research paper thumbnail of Expression of Genes Involved in Lipid Metabolism in Men with Impaired Glucose Tolerance: Impact of Insulin Stimulation and Weight Loss

Journal of Nutrigenetics and Nutrigenomics, 2010

Background:The impaired glucose tolerance (IGT) state is characterized by insulin resistance. Dis... more Background:The impaired glucose tolerance (IGT) state is characterized by insulin resistance. Disturbances in fatty acid (FA) metabolism may underlie this reduced insulin sensitivity. The aim of this study was to investigate whether the prediabetic state is accompanied by changes in the expression of genes involved in FA handling during fasting and in insulin-mediated conditions and to study the impact of

Research paper thumbnail of High fat diet-induced changes in mouse muscle mitochondrial phospholipids do not impair mitochondrial respiration despite insulin resistance

Background: Type 2 diabetes mellitus and muscle insulin resistance have been associated with redu... more Background: Type 2 diabetes mellitus and muscle insulin resistance have been associated with reduced capacity of skeletal muscle mitochondria, possibly as a result of increased intake of dietary fat. Here, we examined the hypothesis that a prolonged high-fat diet consumption (HFD) increases the saturation of muscle mitochondrial membrane phospholipids causing impaired mitochondrial oxidative capacity and possibly insulin resistance. Methodology: C57BL/6J mice were fed an 8-week or 20-week low fat diet (10 kcal%; LFD) or HFD (45 kcal%). Skeletal muscle mitochondria were isolated and fatty acid (FA) composition of skeletal muscle mitochondrial phospholipids was analyzed by thin-layer chromatography followed by GC. High-resolution respirometry was used to assess oxidation of pyruvate and fatty acids by mitochondria. Insulin sensitivity was estimated by HOMA-IR.

Research paper thumbnail of Genetic associations with acute stress-related changes in eating in the absence of hunger

Patient Education and Counseling, 2010

BackgroundAcute psychological stress is associated with eating in the absence of hunger.

Research paper thumbnail of Leptin-adiposity relationship changes, plus behavioral and parental factors, are involved in the development of body weight in a Dutch children cohort

Physiology & behavior, Jan 18, 2008

The development of body weight is determined by different factors, namely genetic, behavioral, pa... more The development of body weight is determined by different factors, namely genetic, behavioral, parental and physiological. To investigate whether genetic, behavioral, parental and physiological factors are involved and the extent of involvement in the development of body weight at ages 12 and 13 y in a Dutch children cohort. In a Dutch cohort of 94 children at ages 12 and 13 y, we determined anthropometric measurements, body composition, leptin concentrations, TFEQ scores, physical activity, as well as 3 polymorphisms, and in the parents we determined anthropometric measurements and TFEQ scores. 11% of the children in the cohort were classified as overweight. The genotype frequency distributions of the PPARy2, GRL and CNTF genes at ages 12 and 13 y were not significantly different for the overweight children compared to the lean children. Overweight children showed higher dietary restraint and disinhibition scores. Overweight children's parents had a higher BMI, dietary restrain...

Research paper thumbnail of The challenge for genetic epidemiologists: how to analyze large numbers of SNPs in relation to complex diseases

BMC genetics, 2006

Genetic epidemiologists have taken the challenge to identify genetic polymorphisms involved in th... more Genetic epidemiologists have taken the challenge to identify genetic polymorphisms involved in the development of diseases. Many have collected data on large numbers of genetic markers but are not familiar with available methods to assess their association with complex diseases. Statistical methods have been developed for analyzing the relation between large numbers of genetic and environmental predictors to disease or disease-related variables in genetic association studies. In this commentary we discuss logistic regression analysis, neural networks, including the parameter decreasing method (PDM) and genetic programming optimized neural networks (GPNN) and several non-parametric methods, which include the set association approach, combinatorial partitioning method (CPM), restricted partitioning method (RPM), multifactor dimensionality reduction (MDR) method and the random forests approach. The relative strengths and weaknesses of these methods are highlighted. Logistic regression ...