Fatty Acid Handling in Mammalian Cells

Abstract

Long-chain fatty acids are crucial for a number of functions in mammals. They are essential components in phospholipids that form biological membranes; they are a very important substrate for energy production in muscle, heart and liver. Fatty acids covalently modify diverse proteins, thereby regulating their interaction with membranes, activity and cellular localisation. Fatty acids function as signalling molecules in metabolic processes, and regulate immune responses through synthesis of eicosanoids and through toll-like receptors. Finally, fatty acids control the expression of a number of important genes. While fatty acids are essential for life, excess fatty acids are seen in obesity and are associated with lipotoxicity. Chronic elevated concentration of saturated fatty acids (palmitic acid, stearic acid) negatively affects metabolic functions in multiple tissues by enhancing production of pro-inflammatory cytokines and reactive oxygen species. On the other hand, n-3 polyunsaturated fatty acids prevent complications of lipotoxicity. Increased fatty acid synthesis in liver also has detrimental effects, including elevated serum triacylglycerol as well as intrahepatic triacylglycerol storage (steatosis) that can progress to steatohepatitis. Hepatic steatosis is strongly associated with insulin resistance. In contrast, augmented lipogenesis in adipose tissue is associated with enhanced insulin sensitivity. This chapter focuses on de novo fatty acid synthesis, uptake of exogenous fatty acid into cells and utilisation of fatty acids for various cellular purposes including regulation of ATP production (oxidation) in mitochondria, energy storage (triacylglycerol synthesis) and signalling.