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Publications
Publications (209)
Food systems in Europe are largely unjust and not sustainable. Despite substantial negative consequences for individual health, the environment and public sector health and care services, large multi-national corporations continue to benefit from the way food systems are designed—perpetuating “Lose–Lose–Lose–Win” food systems that see these large c...
Background:
Lifestyle intervention studies to treat type 2 diabetes (T2D) are on the rise. However, in-depth research is lacking into the dietary changes that participants make.
Methods:
The present study aimed to observe the dietary intake of participants following the group program 'Reverse Diabetes2 Now' (RD2N) over 12 months. The web-based 2...
Leefstijlinterventies bij diabetes type 2 (DM2) blijken op de korte termijn goed te werken. Of ze ook op de langere termijn in ‘real life’-omstandigheden effect hebben is echter nog niet zo duidelijk. De intensieve leefstijlbehandeling Keer Diabetes2 Om van Voeding Leeft blijkt een duurzame gedragsverandering teweeg te brengen. Na 24 maanden gebrui...
Background
Eating problems are highly prevalent in older patients with dementia and as a consequence, these patients are at greater risk of becoming malnourished. Fingerfoods, snacks that can be picked with thumb and forefinger, could be used to counteract malnutrition in patients with dementia. The aim of this feasibility study was to evaluate whe...
Introduction
A wealth of evidence supports short-term efficacy of lifestyle interventions in type 2 diabetes (T2D). However, little is known about long-term effects of lifestyle interventions in real-life settings.
Methods
This observational, single-arm study evaluated long-term impact of ‘Voeding Leeft: Reverse-Diabetes2-Now’, a 6-month multicomp...
Als voorbereiding op het VoedingNLcongres 'Koolhydraten en insulinegevoeligheid' (10 maart 2020) hebben we een expertsessie georganiseerd met professionals afkom stig uit wetenschap en praktijk. We hebben deze experts uitgenodigd om hun visie te geven op verschillende deelvragen omtrent koolhydraten en insulinegevoeligheid, en hen gevraagd om onder...
Objective:
Insulin signaling via phosphoinositide 3-kinase (PI3K) requires PIK3R1-encoded regulatory subunits. C-terminal PIK3R1 mutations cause SHORT syndrome, including lipodystrophy and insulin resistance (IR), surprisingly without fatty liver or metabolic dyslipidemia. We sought to investigate this discordance.
Methods:
The human pathogenic...
Background Eating problems are highly prevalent in older patients with dementia and as a consequence, these patients are at greater risk of becoming malnourished. Fingerfoods, snacks that can be picked with thumb and forefinger, could be used to counteract malnutrition in patients with dementia. The aim of this feasibility study was to evaluate whe...
Background Eating problems are highly prevalent in older patients with dementia and as a consequence, these patients are at greater risk of becoming malnourished. Fingerfoods, snacks that can be picked with thumb and forefinger, could be used to counteract malnutrition in patients with dementia. The aim of this feasibility study was to evaluate whe...
Background
Eating problems are highly prevalent in older patients with dementia and as a consequence, patients are at greater risk of becoming malnourished. Fingerfoods, snacks that can be picked with thumb and forefinger, could be used to counteract malnutrition in patients with dementia. The aim of this feasibility study was to evaluate whether p...
Background Eating problems are highly prevalent in older patients with dementia and as a consequence, these patients are at greater risk of becoming malnourished. Fingerfoods, snacks that can be picked with thumb and forefinger, could be used to counteract malnutrition in patients with dementia. The aim of this feasibility study was to evaluate whe...
Introduction
Prevalence of type 2 diabetes (T2D) is increasing rapidly and lifestyle interventions to reverse diabetes are seen as a possible solution to stop this trend. New practice-based evidence is needed to gain more insight in the actual, and above all scientific, basis for these claims.
Methods
This observational study with a pretest post-t...
Aims:
Intra-uterine growth restriction (IUGR) followed by accelerated postnatal growth is associated with an increased risk of obesity and type 2 diabetes. We aimed to determine central and peripheral insulin sensitivity in mice that underwent IUGR followed by postnatal catch-up growth and investigate potential molecular mechanisms underpinning th...
Vps34 PI3K is thought to be the main producer of phosphatidylinositol-3-monophosphate, a lipid that controls intracellular vesicular trafficking. The organismal impact of systemic inhibition of Vps34 kinase activity is not completely understood. Here we show that heterozygous Vps34 kinase-dead mice are healthy and display a robustly enhanced insuli...
Heterodimeric class IA phosphatidylinositol-3-kinases (PI3K) transduce signals from many receptor tyrosine kinases including the insulin receptor. PI3K recruitment to phosphotyrosines is mediated by Pik3r1 gene products including the most intensely studied PI3K regulatory subunit, p85α, which also binds and regulates the PIP3 phosphatase Pten, and...
All DNA polymerases misincorporate ribonu-cleotides despite their preference for deoxyribonu-cleotides, and analysis of cultured cells indicates that mammalian mitochondrial DNA (mtDNA) tolerates such replication errors. However, it is not clear to what extent misincorporation occurs in tissues, or whether this plays a role in human disease. Here,...
Thyroid hormones (THs) act in the brain to modulate energy balance. We show that central triiodothyronine (T3) regulates de novo lipogenesis in liver and lipid oxidation in brown adipose tissue (BAT) through the parasympathetic (PSNS) and sympathetic nervous system (SNS), respectively. Central T3 promotes hepatic lipogenesis with parallel stimulati...
Thyroid hormones (THs) act in the brain to modulate energy balance. We show that central triiodothyronine (T3) regulates de novo lipogenesis in liver and lipid oxidation in brown adipose tissue (BAT) through the parasympathetic (PSNS) and sympathetic nervous system (SNS), respectively. Central T3 promotes hepatic lipogenesis with parallel stimulati...
Key points
In the Western world, obesogenic diets containing high fat and high sugar (HFHS) are commonly consumed during pregnancy, although their effects on the metabolism of the mother, in relation to feto‐placental glucose utilization and growth, are unknown.
In the present study, the consumption of an obesogenic HFHS diet compromised maternal g...
We investigated the independent and interactive impact of the common APOE genotype and marine n-3 polyunsaturated fatty acids (PUFA) on the development of obesity and associated cardiometabolic dysfunction in a murine model. Human APOE3 and APOE4 targeted replacement mice were fed either a high-fat control diet (HFD) or a HFD supplemented with 3% n...
MPV17 is a mitochondrial inner membrane protein whose dysfunction causes mitochondrial DNA abnormalities and disease by an unknown mechanism. Perturbations of deoxynucleoside triphosphate (dNTP) pools are a recognized cause of mitochondrial genomic instability; therefore, we determined DNA copy number and dNTP levels in mitochondria of two models o...
MPV17 and other factors linked to mitochondrial depletion syndromes are upregulated in non-dividing cells.
(A-B) Steady state levels of R2, TK1, DGUOK, TK2 and p53R2 in proliferating or quiescent control fibroblasts. Proliferating and quiescent panels are directly comparable as they show cropped images from the same blots (samples run on the same g...
Additional references to the supplemental information.
(DOCX)
List of the patients and associated gene mutations analyzed in this study.
(DOCX)
Interpretation of the pattern of mtDNA replication intermediates in mouse liver.
(A) Bubble structures are replication intermediates that include the origin, Y–replication fork arc, SY arcs—supra-Ys. and further interpreted in panel (B); black lines represent DNA, red lines are RNA, black crosses are indicative of blocked restriction sites. The rep...
List of primers employed in the study.
(DOCX)
List of antibodies employed in the study.
(DOCX)
Deoxynucleoside supplementation prevents the mtDNA depletion in MPV17-deficient fibroblasts.
(A) Relative mtDNA copy number of quiescent control or MPV17 deficient fibroblasts supplemented with deoxynucleosides. Where indicated fibroblasts were supplemented with 50 μM of AdR, CdR and GdR or AdR, CdR, GdR and TdR. The amount of mtDNA is expressed re...
Mouse mtDNA samples sequence coverage.
The mitochondrial genome position (x-axis) versus sequence coverage divided by maximum coverage for each sample. The coverage was calculated using a 2 kilobase sliding window average. MtDNA of the WT and KO samples are indicated, respectively, in black and in red.
(TIF)
Increased dNTP pool symmetry in two models of MPV17 deficiency.
Mitochondrial dNTPs levels in mouse liver (left) and quiescent human fibroblasts (right). P values were obtained using Mann-Whitney test (***P<0.001, **P<0.01,*P<0.05, P>0.05—not significant (NS)). The charts are modified from those shown in Figs 2A and 4E.
(TIF)
The expression of several factors involved in nucleotide metabolism is unaffected in brain and kidney of the Mpv17 ablated mouse.
Steady state levels of (A) Ent1, Pnc1 and Pnc2, (B) Tk2, Ak2, Ak3 and Dguok in the brain and kidney of wild-type (WT) and knockout (KO) mice. (C) Representative immunoblot of Sucla2, Suclg1 and Suclg2 proteins (the three...
In late pregnancy, maternal insulin resistance occurs to support fetal growth but little is known about insulin-glucose dynamics close to delivery. This study measured insulin sensitivity in mice in late pregnancy, day (D) 16, and near term, D19, (term 20.5D). Non-pregnant (NP) and pregnant mice were assessed for metabolite and hormone concentratio...
Significance
The mass of white adipose tissue (WAT) in an organism is tightly controlled by the balance of triglyceride (TG) synthesis and catabolism. Here, we show that these opposing pathways communicate. TG catabolism by adipose triglyceride lipase (ATGL) activates peroxisome proliferator-activated receptor gamma (PPAR-γ), a crucial transcriptio...
Background:
Obesity is associated with a hypercoagulable state and increased risk for thrombotic cardiovascular events.
Objective:
Establish the onset and reversibility of the hypercoagulable state during the development and regression of nutritionally-induced obesity in mice, and its relation to transcriptional changes and clearance rates of co...
Hypothalamic ribosomal S6K1 has been suggested as a point of convergence for hormonal and nutrient signals in the regulation of feeding behavior, bodyweight, and glucose metabolism. However, the long-term effects of manipulating hypothalamic S6K1 signaling on energy homeostasis and the cellular mechanisms underlying these roles are unclear. We ther...
Here, we investigated how low density lipoprotein receptor deficiency (Ldlr(-/-)) modulates the effects of testosterone on obesity and related metabolic dysfunctions. Though sham operated Ldlr(-/-) mice fed western-type diet for 12 weeks became obese and showed disturbed plasma glucose metabolism and plasma cholesterol and triglyceride profiles, ca...
Dysregulated glucagon secretion accompanies islet inflammation in type 2 diabetes. We recently discovered that IL-6 stimulates glucagon secretion from human and rodent islets. IL-6 family cytokines require the gp130 receptor to signal. In this study we elucidated the effects of α cell gp130 receptor signaling on glycemic control in type 2 diabetes....
Platelets abundantly express the membrane receptor CD36 and store its ligand thrombospondin-1 (TSP1) in the α-granules. We investigated whether released TSP1 can support platelet adhesion and thrombus formation via interaction with CD36.
Mouse platelets deficient in CD36 showed reduced adhesion to TSP1 and subsequent phosphatidylserine expression....
Significance
Physical exercise causes profound changes in energy metabolism in humans. In this study we show that resting skeletal muscle has a crucial role in the metabolic response to acute exercise. During endurance exercise, selective induction of the protein angiopoietin-like 4 (ANGPTL4) in nonexercising muscle reduces local fatty acid uptake,...
Objective:
The scavenger receptor CD36 facilitates the cellular uptake of long-chain fatty acids. As CD36-deficiency attenuates the development of high fat diet (HFD)-induced obesity, the role of CD36-deficiency in preadipocyte recruitment and adipocyte function was set out to characterize.
Design and methods:
Fat cell size and number were deter...
Glycerol, a product of adipose tissue lipolysis, is an important substrate for hepatic glucose synthesis. However, little is known about the regulation of hepatic glycerol metabolism. Here we show that several genes involved in the hepatic metabolism of glycerol, i.e., cytosolic and mitochondrial glycerol 3-phosphate dehydrogenase (GPDH), glycerol...
Introduction: Congenital central hypothyroidism occurs either as isolated TSH deficiency or in conjunction with other pituitary hormone deficits. Undetected central hypothyroidism is associated with developmental delay in children and adverse cardiometabolic sequelae in adults. Hitherto, mutations in the TRH receptor (TRHR) or TSHβ subunit (TSHB) g...
Oxidative phosphorylation in mitochondria is responsible for 90% of ATP synthesis in most cells. This essential housekeeping function is mediated by nuclear and mitochondrial genes encoding subunits of complex I to V of the respiratory chain. Although complex IV is the best studied of these complexes, the exact function of the striated muscle-speci...
Cox6a2 is not expressed in thermogenic adipose tissues. (A–B) Left panels: Microarray hybridization signals from public data in BAT (A: GSE7623) and a comparison between mesenteric and SC WAT (B: E-MEXP-1636). Right panels: Correlation between Cox6a2 signals and signals for muscle markers and UCP1 in BAT (A) and SC WAT (B).
(TIF)
Accelerated body weight loss of fasted Cox6a2−/− mice. (A–B) Male (A) (n = 10) and female (B) (n = 3–7) mice were deprived of food at 7 am. Throughout the experiment, they had unlimited access to water. Body weight was measured for 36 h. Percentage body weight loss per hour of fasting (slope) is shown on the right. Note that two out of ten male Cox...
Plasma parameters in fed WT and
Cox6a2
−/− mice.
(PDF)
Gene Set Enrichment Analysis.
(PDF)
Gene expression of antioxidant enzymes in
Cox6a2
−/−
vs
WT mice.
(PDF)
Ucp1 and Ucp2 mRNA expression in WAT and gastrocnemius muscle of mice fed a HFD. (A–B) Quantitative RT-PCR was performed on cDNA from white adipose tissue (WAT), (C) and gastrocnemius muscle (gastroc), (D) (n = 5). Gene expression in wild-type mice on a regular diet was set at 1.0 for each individual gene (dashed line). Note that Ucp1 mRNA was not...
Total body composition, food intake and thyroid and pituitary hormones of WT versus Cox6a2−/− mice fed a regular diet. (A–B) % lean mass (A), and % fat mass (B) were assessed by NMR, (C) Food and water consumption measured in 12–16 weeks old mice (n = 4–5). Measurements were performed over a 3-day period, (D) Thyrotropin (TSH) bioactivity (left pan...
Primers and probes used for quantitative PCR.
(PDF)
Supportive Experimental procedures.
(DOCX)
Beta cells adapt to an increased insulin demand by enhancing insulin secretion via increased beta cell function and/or increased beta cell number. While morphological and functional heterogeneity between individual islets exists, it is unknown whether regional differences in beta cell adaptation occur. Therefore we investigated beta cell adaptation...
The spatial relation to adjacent organs was used to divide the pancreas into three parts: DR = duodenal region, GR = gastric region, SR = splenic region.
(TIF)
Congenital central hypothyroidism occurs either as isolated thyroid-stimulating hormone (TSH) deficiency or in conjunction with other pituitary hormone deficits. Undetected central hypothyroidism is associated with developmental delay in children and adverse cardiometabolic sequelae in adults. Hitherto, mutations in the thyrotropin-releasing hormon...
Most studies on TCF7L2 SNP variants in the pathogenesis of type 2 diabetes (T2D) focus on a role of the encoded transcription factor TCF4 in β cells. Here, a mouse genetics approach shows that removal of TCF4 from β cells does not affect their function, whereas manipulating TCF4 levels in the liver has major effects on metabolism. In Tcf7l2(-/-) mi...
Synucleins are a family of homologous proteins principally known for their involvement in neurodegeneration. γ-Synuclein is
highly expressed in human white adipose tissue and increased in obesity. Here we show that γ-synuclein is nutritionally regulated
in white adipose tissue whereas its loss partially protects mice from high-fat diet (HFD)–induce...
Congenital central hypothyroidism occurs either in isolation or in conjunction with other pituitary hormone deficits. Using exome and candidate gene sequencing, we identified 8 distinct mutations and 2 deletions in IGSF1 in males from 11 unrelated families with central hypothyroidism, testicular enlargement and variably low prolactin concentrations...
Objective:
We investigated whether a reduced iso-α acid derived from an extract of Humulus lupulus L., META060, had an effect on weight gain, body composition, and metabolism in a high-fat-diet (HFD) fed mouse model.
Methods:
Weight gain was monitored for up to 20 wk in mice receiving a low-fat diet, an HFD, or an HFD supplemented with META060 o...
In this study, we define a new role for lipocalin prostaglandin D synthase (L-PGDS) in the control of metabolic fuel utilization by brown adipose tissue (BAT). We demonstrate that L-PGDS expression in BAT is positively correlated with BAT activity, upregulated by peroxisome proliferator-activated receptor γ coactivator 1α or 1β and repressed by rec...
To assess the short- and long-term effects of addition of exercise to a very low calorie diet (VLCD) on low-grade inflammation in obese patients with type 2 diabetes mellitus (T2DM).
Twenty seven obese, insulin-dependent T2DM patients followed a 4-month VLCD with (n=13) or without (n=14) exercise and were followed up to 18 months. Anthropometric me...
