High fat diet and obesity are associated with intramuscular lipids accumulation that leads to e.g. insulin resistance (IRES) and type 2 diabetes. The mechanism of the state is unknown. Currenly, research focuses on bioactive lipids: long-chain acyl-CoA, diacylglycerols and ceramides. It’s not clear which lipids play the crucial role induction of IRES. Therefore, I propose a study with in vivo gene silencing of enzymes involved in the lipids synthesis to elucidate the role of the particular lipids on insulin pathway. To measure synthesis rate of the lipids I plan to use a stable isotope labelled FA infusion. Furthermore, in parallel to targeted analyses of mRNA and proteins involved in lipid metabolism and in insulin pathway, we will perform high throughput analyses: transcriptome, proteome and metabolome. The proposed research is related to basic science with a potential of breakthrough discovery that can provide a necessary knowledge for inventing new therapy for IRES or diabetes.