Saturated fatty acids (SFA)(eg palmitate [16: 0]) are almost universally toxic to cells in culture, whereas the monounsaturated fatty acids (MUFA)(eg oleate [18: 1]) are either non-toxic or cytoprotective. The opposing effects of SFA and MUFA have been observed in multiple cell types including islet β-cells, 1 endothelial cells, 2 cardiomyocytes, 3 breast cancer cell lines, 4, 5 and in hepatocyte cell lines as shown by Ricchi et al. in this issue of the Journal. 6 Importantly, the addition of MUFA to cell cultures dosedependently inhibits SFA-induced cell death. Elevated glucose clearly increases the toxicity of palmitate in β-cells, a process called glucolipotoxicity. 1 The role of elevated glucose on lipotoxicity in other cell types has been under-investigated. An understanding of the mechanisms by which SFA are cytotoxic and MUFA are cytoprotective may give us clues to novel therapeutic approaches for relevant conditions, whether by diet or pharmacotherapeutic means. In most circumstances (eg steatohepatitis complicating non-alcoholic fatty liver disease [NAFLD]) the aim will be to inhibit cytotoxicity and/or promote cytoprotection. In some situations, however, inhibition of MUFA-induced cytoprotective mechanisms may have a role (eg in cancer therapy). So, why do the differing fatty acid types behave so differently with respect to cell survival?

Fatty acids and their metabolites have numerous biological functions. 7 Not only are lipids the major form by which energy is stored, they are also involved in cell structure, and participate in intracellular, extracellular and whole animal (endocrine) signaling processes. It should be no surprise, therefore, that the metabolism and behavior of the various types of fatty acids differs greatly. Considering this, it is probable that the mechanisms and/or pathways involved in SFA-induced cytotoxicity will be multiple and differ from those of MUFA-mediated cytoprotection.