Use of Lipids as Energy Substrates

Abstract

Complex lipids and their fatty acid components have important biological activities and are involved in the regulation of many metabolic and physiological processes. Fatty acids are important energy sources and upon complete β-oxidation yield more energy per mole and per carbon atom than glucose. Fatty acid β-oxidation occurs mainly in the mitochondria, and there are specific mechanisms for transporting fatty acids from the cytosol to the mitochondrial matrix to enable their oxidation. Ensuring fatty acid availability for oxidation reduces the need for glucose provision. Fatty acids in foods and in formulas used for nutrition support are esterified into triacylglycerols. There are specific mechanisms for releasing fatty acids from triacylglycerols provided orally and for taking these up into enterocytes. These involve coordinated physical, chemical and enzymatic activities operating from the mouth to the small intestine. In healthy people these processes are very efficient, but they can be disrupted by injury, illness or disease, including critical illness, meaning that fatty acid availability can be decreased in these situations. The products of triacylglycerol digestion and absorption ultimately appear in the bloodstream as triacylglycerols in lipoproteins called chylomicrons. Fatty acids are removed from chylomicrons by the action of lipoprotein lipase, which is promoted by insulin, and can be stored in adipose tissue following their re-esterification into triacylglycerols. In stress states or times of limited glucose availability, fatty acids are released from stored triacylglycerols and appear in the bloodstream as non-esterified fatty acids. These are the substrates for β-oxidation and energy generation. Lipid emulsions used in intravenous nutrition support are metabolised similarly to chylomicrons, but they need to acquire proteins from native lipoproteins to enable this to happen. ESPEN guidelines recommend intravenous lipid infusion in critically ill patients where enteral feeding is not possible. However, excess rates of lipid infusion can lead to hypertriacylglycerolemia and can disrupt organ function, and therefore the rate of lipid infusion needs to be controlled and limited. The critically ill patient displays alterations in lipid metabolism and lipid utilisation that result from insulin resistance, the stress response, inflammation and nutrition support. Fatty acids are the preferred fuel in critical illness, and there is an increase in whole body fat oxidation. However, fatty acid availability may be in excess of needs, and fatty acids not oxidised may be incorporated into triacylglycerols in the liver resulting in hepatic steatosis and hypertriacylglycerolemia, which may be promoted by lipid infusion and by impaired triacylglycerol clearance. Whether these events happen or not is determined by the specific state of the individual critically ill patient. Because the fatty acid components of triacylglycerols are biologically active, the precise composition of lipid used in artificial nutrition support of critically ill patients may affect metabolic, physiological and clinical outcomes.