Lipid fuel metabolism in health and disease.

Rates of adipose tissue lipolysis are increased in critically ill patients, thus increasing the systemic supply of free fatty acids. This increase in the availability of free fatty acids is probably mediated by various factors including increases in counterregulatory hormones and tumor necrosis factor alpha. The cytokines tumor necrosis factor and interleukin-1 also promote de novo lipogenesis in the liver and may be responsible for impaired triglyceride removal in peripheral tissues; these effects together contribute to the hypertriglyceridemia often seen in septic states. This hypertriglyceridemia may have a teleologic basis, because triglyceride-rich lipoproteins have been shown to bind and inactivate endotoxin. When present in excess, free fatty acids may be responsible for tissue injury in the cold-stored liver allograft, in ischemic-reperfusion cardiac injury, and in ischemic brain injury. Hypoketonemia commonly occurs in septic states and may be due to the combination of a defect in hepatic ketogenesis and accelerated ketone body uptake by peripheral tissues. Both tumor necrosis factor and interleukin-1 have a hypoketonemic effect in animals. Whether ketone bodies have significant protein-sparing properties remains controversial.