Free fatty acid regulation of glucose-dependent intrinsic oscillatory lipolysis in perifused isolated rat adipocytes

Abstract

Free fatty acids (FFAs) and glycerol oscillate in plasma. This study examined intrinsic lipolytic oscillations within adipocytes. Rat adipocytes were perifused with Krebs-Ringer bicarbonate buffer: 1) +/- 2 mmol/l glucose; 2) +1 micromol/l isoproterenol +/- 2 mmol/l glucose; 3) + increasing oleate; and 4) + increasing percent BSA. At 2 mmol/l glucose, there were 9 +/- 1 glycerol, FFAs, and lactate pulses per hour with a pulse duration of 5 +/- 1 min. Lipolytic stimulation caused a 50-80% increase in the amplitude of lipolytic oscillations. Removal of glucose caused a 40-70% decrease in the amplitude of lipolytic oscillations and disturbed the pulsatility. Exogenous FFAs suppressed lipolysis and oscillatory amplitude, possibly because of increased cytosolic long-chain coenzyme A (LC-CoA). Increasing percent BSA increased stimulated lipolysis and oscillatory amplitude, possibly because of decreased intracellular LC-CoA. These data show, for the first time, intrinsic lipolytic oscillations, which are glucose dependent and modulated by FFAs. We hypothesize that lipolytic oscillations are driven by oscillatory glucose metabolism, which leads to oscillatory relief of LC-CoA inhibition of triglyceride lipase(s). The results contribute to the understanding of physiological and biochemical regulators of lipolysis, such as glucose and FFAs. Lipolytic oscillations may be beneficial in the delivery of FFAs to liver, pancreas, and other tissues.