α-Tocopheryl-phosphate regulation of gene expression in preadipocytes and adipocytes

A correct function of adipocytes in connection with cellular fatty acid loading and release is a vital aspect of energy homeostasis; dysregulation of these reactions can result in obesity and type 2 diabetes mellitus. In addition, adipocytes have been proposed to play a major role in preventing lipotoxicity by removing excess fatty acids from the circulation and converting them into triglycerides and thus decreasing the exposure of other cells to their potentially harmful effects. We report here that the addition of α-tocopheryl phosphate (but not α-tocopherol) to NIH3T3-L1 preadipocytes transcriptionally activates a set of genes TRB3 (Tribbles Homolog 3), Sestrin-2 (SESN2), and Insulin-Induced Gene 1 (INSIG1)] potentially preventing fat accumulation in these cells. In contrast, in differentiated adipocytes, α-tocopheryl phosphate is responsible for the transcriptional inhibition of the same genes, possibly facilitating fat uptake and storage. In conclusion, it appears that in proliferating preadipocytes α-tocopheryl phosphate foils fat accumulation, whereas in adipocytes it enhances it. These processes may be relevant in the regulation of excess fat accumulation and in prevention of lipotoxicity.