Submitted to: Biofactors
Publication Type: Peer reviewed journal
Publication Acceptance Date: 8/31/2012
Publication Date: 11/1/2012
Citation: Lirangi, M., Meydani, M., Zingg, J., Azzi, A. 2012. Alpha-tocopheryl-phosphate regulation of gene expression in pre-adipocytes and adipocytes. Biofactors. 38(6):450-457. Interpretive Summary: The biological function of vitamin E (alpha-tocopherol) has been investigated intensely in the last 50 years. Vitamin E’s role was initially understood as a fertility vitamin in rodents. Later, this function was attributed to its role as an antioxidant, a substance that removes potentially damaging agents in a living being. Further research is needed to clarify this role. Recently, a new form of vitamin E called alpha-tocopheryl phosphate was found in human blood and tissues, and human supplementation with alpha-tocopheryl phosphate increases its concentration in the blood. The present study was designed to understand the biological function of alpha-tocopheryl phosphate action as the active form of its parent vitamin form, alpha-tocopherol. In a number of experiments in cells studying this new form of vitamin E and its protection against inflammation and heart disease, alpha-tocopheryl phosphate was shown to be more effective than alpha-tocopherol. Our study showed that alpha-tocopheryl phosphate (but not alpha-tocopherol) in fat cells activates a set of genes that help prevent cell expansion and fat accumulation in them. These cell studies indicate the possibility that alpha-tocopheryl phosphate may regulate accumulation of fat in the body, which may have important outcomes for excessive overweight, heart disease and inflammation.
Technical Abstract: 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 alpha-tocopheryl phosphate (but not alpha-tocopherol) to NIH3T3-L1 pre-adipocytes transcriptionally activates a set of genes TRB3 (Tribbles Homolog 3), Sestrin-2, and Insulin Induced Gene 1 (INSIG)] potentially preventing fat accumulation in these cells. In contrast, in differentiated adipocytes, alpha-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 pre-adipocytes alpha-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.