Dietary lipids, sex and age in pathogenesis of metabolic syndrome

Metabolic syndrome refers to a combination of several metabolic risk factors including insulin resistance, central obesity, dyslipidaemia and hypertension. Dysfunction of lipid metabolism is a key component in the development of metabolic syndrome and the prevalence of metabolic syndrome is strongly associated with the severity of obesity. Therefore, dietary intervention could be important strategy for the prevention of metabolic syndrome and associated diseases. Obesity arises from a sustained positive energy balance which triggers a pro-inflammatory response. The enhanced secretion of pro-inflammatory peptides promotes penetration of inflammatory cells such as macrophages and lymphocytes resulting in alteration of microenvironment within adipose tissue. This causes law-grade chronic inflammation and lipid spill-over from the adipose to the liver, muscle and pancreas resulting in glucotoxicity and lipotoxicity. These disturbances culminate in impaired insulin signaling, dysregulated glucose homeostasis and consequent development of insulin resistance. Chronic inflammation and insulin resistance are now recognized as contributing factors to many modern diseases such as insulin non dependent diabetes mellitus, cardiovascular diseases, Alzheimer disease and cancer. To achieve project objectives we will investigate several interactions that take place in metabolic syndrome pathogenesis: A) Influence of dietary n3/n6 ratio and DHA as a preventive mechanism on the severity of metabolic syndrome with sex as additional variable, B) Influence of dietary n3/n6 ratio and DHA on therapy of induced metabolic syndrome with sex as additional variable, C) Parental transmission of predisposition to obesity-related disorders to their offspring and influence of offspring diet on severity of metabolic disorders before and after sexual maturity, D) Interaction between age and metabolic syndrome with sex and dietary energy (HFD vs. low calorie) as an additional variables and E) Cancer lipid metabolism and cancer markers of lipid origin as well as possible link between obesity, metabolic syndrome, low grade chronic inflammation and cancer. Finally, the integration of gained knowledge from all experiments will allow us to suggest new approaches to dietary prevention and therapy of metabolic syndrome and to better understand underlying link between obesity related chronic inflammation and cancer.