1,2-Dicinnamoyl-sn-glycero-3-phosphocholine Improves Insulin Sensitivity and Upregulates mtDNA-Encoded Genes in Insulin-Resistant 3T3-L1 Adipocytes: A Preliminary Study

Background: Insulin resistance is a condition characterized by a reduced biological response to insulin. It is one of the most common metabolic diseases in modern civilization. Numerous natural substances have a positive effect on metabolism and energy homeostasis including restoring the proper sensitivity to insulin. There may be several possible mechanisms of action. In the present study, we elucidated two natural compounds with an impact on insulin signaling in IR adipocytes involving mitochondria. Methods: Mature 3T3-L1 adipocytes with artificially induced insulin resistance by palmitic acid (16:0) were used for the study. Cinnamic acid and 1,2-dicinnamoyl-sn-glycero-3-phosphocholin (1,2-diCA-PC) were tested at three concentrations: 25 μM, 50 μM, and 125 μM. The number of mitochondria and the expression of genes encoded by mtDNA were elucidated in control and experimental cells. Results: Experimental cells treated with 1,2-diCA-PC displayed increased insulin-stimulated glucose uptake in a dose-dependent manner, accompanied by an increase in mtDNA copy number. Moreover, in experimental cells treated with 1,2-diCA-PC at a concentration of 125 μM, a significant increase in the expression level of all analyzed genes encoded by mtDNA compared to control cells was observed. Our study showed a relationship between improved cellular sensitivity to insulin by 1,2-diCA-PC and an increase in the number of mitochondria and expression levels of genes encoded by mtDNA. Conclusions: To summarize, the results suggest the therapeutic potential of cinnamic acid derivative 1,2-diCA-PC to enhance the insulin sensitivity of adipocytes.