Diet-induced metabolic dysfunction
Though the link between obesity and the development of metabolic and (cardio) vascular disorder like type 2 diabetes, atherosclerosis and chronic kidney disease is unrefuted, the etiology of these pathologies remains largely elusive. The studies presented in this thesis focused on how dietary fat and cholesterol contribute to the development of metabolic dysfunction in the adipose and hepatic tissues, how this is linked to elevated inflammatory and lipid factors in the bloodstream and how consequently these factors contribute to pathologies of the small and large vessels. We provide evidence that inflammation in the adipose tissue has a greater contribution to systemic inflammation and the development of type 2 diabetes compared to the liver. These findings suggest that anti-inflammatory strategies should best focus on the adipose tissue. One way of accomplishing this is by chronic consumption of anti-inflammatory substances parallel to the nutrients that trigger metabolic dysfunction. Polyphenol compounds found at high concentrations in certain fruits and vegetables, and other natural products like tea leafs, have shown promising results in this perspective. Here, in contrary to other groups, we could not show their long-lasting anti-inflammatory effects at either the organ level (adipose tissue) or the bloodstream. This discrepancy might be explained by the relative low dosage applied or the organ assessed. But their effect may also depend on the dietary trigger applied: we show that the same polyphenols do have a beneficial effect if not dietary fat but cholesterol is the trigger for metabolic dysfunction. This thesis stresses the importance of an integrative, systemic view on diet-induced metabolic dysfunction and its associated pathologies.