Effects of omega6/omega3 PUFAs ratio on adipocyte phenotype conversion from white to brite

White adipose tissue (WAT) and brown adipose tissue (BAT) are strongly involved in energetic homeostasis. The first stores energy under the form of triglycerides and releases it on supply, whereas the second dissipates energy in order to produce heat. Recently it was discovered a third type of adipocyte called beige or brite (for brown-in-white) adipocyte. These adipocytes are brown adipocytes located not in BAT but as islets in WAT. They are thermogenically functional and characterized by the expression of UCP1, an uncoupling protein able to dissipate proton gradient of respiratory chain in order to produce heat to the detriment of ATP synthesis. Increase of brite adipocytes in adults could represent a potential strategy to induce weight loss and hence to fight obesity and associated diseases. Recent studies demonstrate that dietary fat uptake, in particular polyunsaturated fatty acids (PUFAs), influences adipose tissue development and the conversion of white to brite adipocytes. This means that a wrong nutritional intake could lead to obesity. To be more specific, it was discovered that ω6-PUFAs prevent the ¿browning¿ process, instead ω3-PUFAs seem to reverse ω6 effects contributing to brite cell development. The present thesis is aimed at studying the effect of the ω6/ω3 PUFAs ratio (equal to 4 which is the recommended nutritional intake) during the conversion process from white to brite adipocytes in vitro using a specific human cellular model: hMADS cells (human Multipotent Adipose-Derived Stem cells) deriving from WAT of new-born. It has been used arachidonic acid (ARA) which is the main ω6 PUFA metabolized by mammals and deriving from linoleic acid (LA), whereas eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been used as ω3PUFAs deriving from α-linolenic acid (LNA). These PUFAs are metabolized in adipocytes in oxygenate derivatives crucial for cell function and signalling. The results confirmed the adverse effects of ARA in vitro already demonstrated in precedent studies and show that EPA alone has no impact on conversion process but it was able to reverse the adverse effects of ARA. Deeper analysis of prostaglandin synthesis and signalling pathways have demonstrated that EPA reverses ARA effect by competition at the level of cyclooxygenase enzymes. In conclusion, in vitro studies confirmed in vivo results, meaning that a ω6/ω3 PUFAs ratio equal to 4 has a positive effect on white to brite adipocytes conversion process and that it could be used to propose a correct and balanced diet to obese patients in order to increase their energy expenditure.