Abstract

The most striking and possibly the most important effect of the catecholamines on lipid metabolism lies in their ability to accelerate acutely the mobilization of FFA from adipose tissue. This effect is attributable to hormone-stimulated conversion of an inactive lipase in adipose tissue to its active form. A number of lines of evidence strongly implicate cyclic 3',5'-AMP in this activation, as described in more detail in subsequent papers of THIS SYMPOSIUM.

It has also been shown that lipase in adipose tissue is subject to inactivation, which can be demonstrated both in the intact tissue and in homogenates. Because the effective lipase activity is thus determined by the balance of a complex dynamic system for activation and inactivation, the mechanisms for effecting net changes in lipase activity can be quite different in different circumstances. Clarification of the mechanisms involved will be difficult until further progress has been made in isolating and characterizing the several enzyme systems involved.

Several metabolic consequences flow from the primary effect of catecholamines on FFA mobilization. The uptake and utilization of FFA is probably increased in all of the peripheral tissues. Recent studies using ascites tumor cells as a model system indicate that the relevant parameter governing FFA uptake is the molar ratio of FFA to albumin. These studies show that the subsequent rate of utilization of FFA for esterification and oxidation to CO₂ is a function of the steady state "load" of FFA on the cell, the latter in turn being a function of the molar ratio of FFA to albumin in the bathing fluid.

The consequences of accelerated uptake in the liver are several: 1) a tendency to deposition of triglycerides, of relevance in the development of fatty liver; 2) an increase in the rate of ketone body production, of relevance to the ketotic states in fasting and in diabetes; 3) a stimulation of the rate of output of lipoproteins into the plasma, of relevance in determining plasma levels of cholesterol, phospholipids and triglycerides. Since the adipose tissue can take up significant amounts of triglycerides carried in lipoproteins, a mechanism is available by which fatty acids mobilized in excess of current requirements can find their way back to the depot triglyceride stores, i.e., there is probably a physiologic fatty acid transport cycle.

The rate of turnover of this cycle is increased by the catecholamines, and the rates of the several metabolic processes flowing from accelerated FFA mobilization are simultaneously increased. Thus, many changes in lipid metabolism, the end results of catecholamine administration or of excessive autonomic nervous system activity, can be understood as secondary results of accelerated FFA mobilization.