The recent epidemic of obesity in Western societies parallels the increase in the Metabolic Syndrome (MetS) and is associated with increased risk for type 2 diabetes and cardiovascular disease. The MetS is defined by a combination of abnormalities including abdominal obesity, increased fasting plasma glucose, increased plasma triglycerides, increased blood pressure and decreased plasma HDL-cholesterol. Since, by definition the MetS is a multifactorial disease, MetS patients will present with varying combinations and degrees of abnormalities. Moreover, a considerable fraction of obese individuals will not develop metabolic syndrome and patients with the metabolic syndrome will differ with respect to the pathology they develop (cardiovascular disease, type 2 diabetes or both).
To optimize interventions and ultimately develop prevention strategies, it is important to identify subgroups of patients based on traditional and novel disease parameters. Metabolomics of well defined patient sub-groups, but also specific animal models, may reveal important hints relevant for risk modulation, especially when combined with extensive (cardio)vascular genetic and genomics analyses (from population and disease based cohorts). The underlying hypothesis is that the homeostasis and interaction between glucose and fat metabolism within and between various organs (liver, muscle, adipose tissue) is disturbed and determines the pathophysiology of obesity and ultimately the metabolic syndrome, type 2 diabetes mellitus and cardiovascular disease.
The aim of this project is to use a metabolomics-driven systems biology approach to metabolic syndrome to address:
- What are the mechanisms causing tissue specific insulin resistance?
- What are the causes behind different phenotypes in obese people?
- Why do some obese develop diabetes, others not?
- Why do some obese people show inflammation characteristics, others do not?