MODIFICATION OF ENERGY-REQUIRING PROCESSES DURING LIPOLYSIS

Abstract

Studies from this laboratory have shown that lipolytic agents produce an inhibition of K+ and α-aminoisobutyric acid (AIB) uptake in fat cells. Furthermore, these agents were also found, in separate experiments, to decrease intracellular ATP levels. It was hypothesized that an intermediate in both these effects was the level of intracellular fatty acids (CAFA). The present study was undertaken to substantiate this hypothesis. A method has been developed for measuring K+ or AIB uptake, ATP, fatty acid (FA) and glycerol release, CAFA levels on a single sample of incubated fat fells in order to establish the exact sequence of events, particularly the relationship between the fall in ATP and the inhibition of energy-dependent K+ and AIB transport. The following sequence in time was observed when cells were exposed to adrenaline: 1) within 1 min, glycerol was released and CAFA levels rose; FA release was not detected until 3 min; 2) CAFA levels then continued to rise slowly with time as lipolysis proceeded at linear rates. This pattern was observed until a critical extracellular ratio of FA released to albumin present of 3-4/1 was reached; 3) at that time the rate of CIFA increase became larger while glycerol and FA output slowed; 4) following this second phase of the CAFA increase, an ATP drop was observed which slightly preceeded or coincided with the first appearance of decreases in K+ and AIB uptake. The drop in ATP and the inhibition of K+ and AIB transport occured at a time when the FA to albumin ratio was 5-6. It is concluded that the observed sequence of events is compatible with the hypothesis that increased CAFA levels ultimately lead, by an as yet unknown mechanism, to a decrease in ATP levels and energy-requiring functions such as K+ and AIB transport. The possibility that such mechanisms represent a feedback system for control of lipolysis will be discussed.