Minor dietary components with proven biological effects play an important role in the complex treatment strategy of obesity-related diseases, however our knowledge regarding the mechanisms of their action is relatively limited. The aim of this project is to identify novel mechanisms behind the beneficial effects of omega-3 in patients with type 2 diabetes mellitus (DM), i.e. the only dietary component with clearly demonstrated beneficial effects on dyslipidemia and cardiovascular mortality and morbidity in the diabetic patients.
Based on our results in a mouse model of metabolic syndrome (Kuda et al. 2009. Diabetologia; Horakova et al. 2012. PLoS One; Kus et al. 2011. PLoS One), and by taking advantage of available clinical data and biological materials (plasma, adipose and muscle tissue) collected during the previous randomized, placebo-controlled, intervention study in DM patients treated with metformin (6-month-long intervention; groups, n=15: placebo, omega-3, placebo+pioglitazone, omega-3+pioglitazone), we focus on:
- novel regulatory mechanisms (adipokines/cytokines, lipid mediators, endocannabinoids), through which omega-3 affect lipid metabolism and mitigate low-grade chronic inflammation and accumulation of adipose tissue
- mechanisms, which differentiate the effects of omega-3 and pioglitazone on insulin sensitivity in patients; and possible improvements of glucose homeostasis in response to a modulation of incretin system by omega-3
- identification of novel markers of sensitivity to treatment, based on targeted metabolomic analysis in plasma of patients.
Project will help to understand the mechanisms, by which omega-3 normalize lipid metabolism and mitigate low-grade inflammation in patients with DM, specifically in those treated with metformin (or metformin + pioglitazone). The results will help to
- rationalize the use of omega-3 in the treatment of DM patients and in the prevention of cardiovascular diseases in these patients
- establish a personalized treatment of the patients.
Supported by the Ministry of Health of the Czech Republic (NT13763-4; 2012-2015; PI: Jan Kopecký, MD, DSc; collaborator: prof. Terezie Pelikánová, MD, DSc, Diabetes Centre, IKEM, Prague).
