Depression and cardiovascular disease (CVD) are among the most prevalent health problems worldwide, with a significant burden of disease. Both conditions are associated and thought to be mediated... Show moreDepression and cardiovascular disease (CVD) are among the most prevalent health problems worldwide, with a significant burden of disease. Both conditions are associated and thought to be mediated by the metabolic syndrome (MetSyn), a cluster of cardiovascular risk factors (waist circumference, blood sugar, cholesterol, triglycerides, blood pressure) and related parameters (BMI, waist-hip-ratio and LDL-cholesterol). Better insights in this association are important in order to better prevent and treat both conditions. This thesis focuses on the association between depression and metabolic disturbances. The results show that there is a significant and longitudinal and bidirectional association between depression and obesity, which is most pronounced among those with a clinical diagnosis depression. When subjects are approached not based on the presence or absence of the diagnosis, but based on the most prevalent symptoms, results show that only __Somatic Arousal__ symptoms (palpitations, dizziness, tension, shortness of breath) are associated with most MetSyn components. Comparing depressed inpatients to depressed outpatients, inpatients show more adverse metabolic disturbances in the lipid-spectrum, while blood pressure is more favorable. Further, inpatients show higher cortisol levels, which are considered to be a measure of the HPA-axis, an important stress-system in the onset and natural course of depression. Show less
Gast, K.B.; Heijer, M. den; Smit, J.W.A.; Widya, R.L.; Lamb, H.J.; Roos, A. de; ... ; NEO Study Grp 2015
In this thesis, we evaluated the acute and more long-term effects of different weight loss strategies; pure calorie restriction by very low calorie diet and gastric banding, versus the drastic... Show moreIn this thesis, we evaluated the acute and more long-term effects of different weight loss strategies; pure calorie restriction by very low calorie diet and gastric banding, versus the drastic surgical procedure Roux-en-Y gastric bypass. Moreover, we found differences between NGT and T2DM subjects at baseline, which enable us to better be able to dissect the subsequent effects of the procedures. To our surprise, and in contrast to previous studies, we observed no additional effect of the RYGB as compared to calorie restriction, on our main outcome parameters: postprandial glucose, insulin and the gut peptide levels three weeks after surgery. Furthermore, both restrictive and RYGB induced weight loss resulted in comparable effects on the lipidome, circulating thyroid hormone levels and the autonomic nervous system. For these outcome parameters, it seems that calorie restriction is the common denominator of the effect of the different weight loss strategies on the short term. Clearly distinct effects of RYGB, however, were seen on bile salt, FGF21 and glucagon levels in response to food intake. Although neither the exact mechanisms, nor the eventual metabolic effect are as yet clear, the gut-liver-pancreas axis may be an important mediator of the effect of the RYGB Show less
This thesis investigates the role of adipose tissue inflammation in joint diseases such as osteoarthritis (OA) and rheumatoid arthritis (RA) . In the first part, we show that baseline levels of... Show moreThis thesis investigates the role of adipose tissue inflammation in joint diseases such as osteoarthritis (OA) and rheumatoid arthritis (RA) . In the first part, we show that baseline levels of circulating adiponectin can predict radiographic progression in patients with early RA. In contrast, in patients with hand OA, this association appears protective. Therefore, to obtain insight into the mechanisms underlying these associations, we investigated the high-molecular-weight isoform of adiponectin (hmwAPN), which is one of the most biologically active isoforms of adiponectin. We show that the associations of total adiponectin with radiographic progression are not mediated by hmwAPN, in either RA or HOA. In the second part, we present the immunological characterization of the infrapatellar fat pad (IFP), a joint associated adipose tissue, in patients with advanced knee OA. We observed profound differences in secreted inflammatory factors and immune cell composition between the IFP and paired subcutaneous adipose tissue samples. Interestingly, we observed obesity-related changes in the IFP phenotype, and in macrophages and adipocytes, Therefore, we investigated the modulatory effects of adipocytes on the phenotype of human macrophages in vitro and we observed that adipocyte-derived lipids can mediate the obesity-related changes in the phenotype of adipose tissue macrophages in humans Show less
This thesis describes the pathophysiology of insulin resistance in the South Asian population and comprises studies on pharmacological and weight loss interventions in insulin resistant patients.... Show moreThis thesis describes the pathophysiology of insulin resistance in the South Asian population and comprises studies on pharmacological and weight loss interventions in insulin resistant patients. Because of the increasing number of patients with obesity and T2DM, more research is needed to identify patients at risk of developing T2DM and to elucidate specific therapeutic targets to improve insulin resistance. For now, the prevention of overweight and obesity is the most essential step in the fight against the worldwide obesity and T2DM epidemic Show less
The first aim of this study was to provide norms for the Eating Disorder Examination Questionnaire (EDE-Q) in a diverse and large clinical sample of individuals with an eating disorder (ED), and a... Show moreThe first aim of this study was to provide norms for the Eating Disorder Examination Questionnaire (EDE-Q) in a diverse and large clinical sample of individuals with an eating disorder (ED), and a general population sample without an ED. Norms for individuals with obesity without an ED were also provided, as a more relevant comparison group for individuals with binge eating disorder. The second aim was to investigate the discriminative validity of the EDE-Q. A sample of females with an ED (N=935), women from the general population without an ED (N=235), and obese females without an ED (N=321) completed the EDE-Q Explorative factor analyses did not support the theorized four subscales of the EDE-Q. Norms for EDE-Q global scores were provided for each of the three samples. Within the ED sample, norms were provided separately for patients with different ED diagnoses. Receiver operating characteristic analyses showed the EDE-Q global score to be highly accurate in discriminating individuals with an ED from those without, and moderately accurate in discriminating individuals with binge eating disorder from those with obesity. The presented norms contribute to a more accurate interpretation of EDE-Q scores, providing an index of the severity level of ED psychopathology. Furthermore, these norms can be used to assess clinical significant change during treatment. In addition, this study demonstrates that the EDE-Q when using its global score, is a valid instrument to assess levels of ED psychopathology. (C) 2012 Elsevier Ltd. All rights reserved. Show less
The introduction of systems biology in combination with the profiling of numerous biochemical components (e.g. lipid metabolites, herbal products) enables the study of living systems from a... Show moreThe introduction of systems biology in combination with the profiling of numerous biochemical components (e.g. lipid metabolites, herbal products) enables the study of living systems from a holistic perspective. In this thesis we explored systems biology-based platforms to investigate the therapeutic effects of chemical drugs and herbal medicines on animal models with high-fat diet-induced obesity and genetic manipulated diabetes. The aim of the work was to better understand the working mechanisms of both treatments on metabolic syndrome from a holistic point of view and to evaluate the potentials of __omics__ technologies to this effort. Our results showed that lipidomics approach with appropriate bioinformatics tools are essential to describe the global, dynamic metabolic response of living systems, e.g. from homeostasis via sub-optimal health and ultimately to dysfunction. These studies pointed hints to disco ver lipid biomarkers in relation to health promotion and disease prevention and facilitated the understanding of the complex regulatory mechanisms in humans or animals. Particularly, the introduction of the systems biology view will not only provide in-depth insights into the multi-target synergetic effects (which have hardly been used in modern drug discovery) but also can bridge Chinese Medicine (multi-target therapy) and Western Medicine (molecular pharmacology). Show less
Overgewicht en obesitas kunnen leiden tot insulineresistentie (type 2 diabetes mellitus) en hyperlipidemie, een risicofactor voor atherosclerose (aderverkalking). Obesitas gaat ook gepaard met de... Show moreOvergewicht en obesitas kunnen leiden tot insulineresistentie (type 2 diabetes mellitus) en hyperlipidemie, een risicofactor voor atherosclerose (aderverkalking). Obesitas gaat ook gepaard met de ontwikkeling van een chronische ontsteking in vetweefsel en lever. Met dit promotieonderzoek laten we met behulp van onderzoek in muizen zien dat ontsteking een belangrijke rol speelt in het metabolisme en transport van vetten. We bekijken ook welk effect dit heeft op de ontwikkeling van atherosclerose en type 2 diabetes. In het eerste deel van dit promotieonderzoek laten we zien dat ontsteking een belangrijke rol speelt in vetmetabolisme en atherosclerose. De ontstekingsremmer aspirine zorgde voor een verlaging van de hoeveelheid vet in het bloed. Activatie van een onsteking in de lever leidde juist tot een verhoging van vet in het bloed, wat de ontwikkeling van atherosclerose in de vaatwand verergerde. In het tweede deel van dit promotieonderzoek bestuderen we het belang van het inflammasoom/caspase-1 complex (betrokken bij ontstekingsprocessen) in obesitas, insulineresistentie en vetmetabolisme. We laten zien dat muizen die een deel van dit eiwit-complex missen, beschermt zijn tegen de ontwikkeling van obesitas en insulineresistentie. Het inflammasoom/caspase-1 complex lijkt daarmee een potentieel target voor de behandeling van obesitas, insulineresistentie en type 2 diabetes. Show less
