Rapid socio-economic growth accelerates urbanization in Indonesia, which changes many aspect of human lives, and potentially affect disease prevalence and outcome. This thesis aims to investigate... Show moreRapid socio-economic growth accelerates urbanization in Indonesia, which changes many aspect of human lives, and potentially affect disease prevalence and outcome. This thesis aims to investigate the impacts of urbanization on human health, especially metabolic health and allergic disease, by incorporating many aspects of scientific investigation. Our cluster-randomized-controlled trial showed that, helminth infection, a characteristic feature of rural areas, and anthelmintic treatment, could significantly affect metabolic profiles and hormones. Thus, the ongoing deworming program in Indonesia require in parallel, monitoring of the metabolic health. Additionally, based on our prospective cohort study and analysis on a large scale nationally representative data, although Indonesian rural populations have relatively better metabolic profiles compared to urban, lifelong residence in rural areas does not protect their community members from adverse metabolic changes due to urbanization. Next, we observed that majority of individuals with diabetes in Indonesia were undiagnosed and untreated, especially in rural populations, which warrants extensive action plan from all related stakeholders. Lastly, high-dimensional data analyses on the systemic and nasal mucosal immune profiles revealed a stronger inflammatory immune responses in the nasal mucosal of Indonesian urban young adults with allergic rhinitis compared to their rural counterparts. Show less
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 was to combine metabolomics and Chinese medicine (CM) diagnosis to search for biomakers or metabolic profiles to subtype of type 2 diabetes (T2DM). An explorative study of 50 males with... Show moreThis thesis was to combine metabolomics and Chinese medicine (CM) diagnosis to search for biomakers or metabolic profiles to subtype of type 2 diabetes (T2DM). An explorative study of 50 males with pre-diabetes was designed and two subtypes (A and B) could be identified by urine metabolomics. More metabolic disturbances were indicated in subtype B. The effects of rimonabant and a multi-component preparation (SUB885C), both with reported effects of regulating weight and the improvement on metabolic risks, were assessed by lipidomics on ApoE*3Leiden.CETP Mice. A 4-week rimonabant intervention brought a significant weight reduction, but moderate effects on lipid profile. SUB885C was able to produce multiple anti-atherogenic changes in lipids of the mice to improve metabolic parameters. A combined approach of lipidomics, biochemistry and herbal component profiling was used to evaluate the effects of the ginseng roots of 3__6 years on the regulation of dyslipidemia in diabetic Goto-Kakizaki rats. The more than 4 year ginseng proved to be valuable for drug development to regulate lipids. To conclude, the early metabolomics investigations performed in this thesis converged analytical bioscience, clinical approach and the diagnostic perspectives in other health system to provide the systems biology view on the pre-stage of T2DM. 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
