Getty-Kaushik Lisa, Richard Ann-Marie T, Corkey Barbara E
Obesity Research Center, Department of Molecular Medicine, Boston Medical Center, EBRC 840, 650 Albany St., Boston, MA 02118, USA.
Diabetes. 2005 Mar;54(3):629-37. doi: 10.2337/diabetes.54.3.629.
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.
游离脂肪酸（FFAs）和甘油在血浆中呈振荡变化。本研究检测了脂肪细胞内源性脂解振荡情况。用 Krebs-Ringer 碳酸氢盐缓冲液对大鼠脂肪细胞进行灌流：1）±2 mmol/L 葡萄糖；2）+1 μmol/L 异丙肾上腺素±2 mmol/L 葡萄糖；3）+ 逐渐增加的油酸；4）+ 逐渐增加的牛血清白蛋白（BSA）百分比。在 2 mmol/L 葡萄糖浓度下，每小时有 9±1 次甘油、游离脂肪酸和乳酸脉冲，脉冲持续时间为 5±1 分钟。脂解刺激导致脂解振荡幅度增加 50 - 80%。去除葡萄糖导致脂解振荡幅度降低 40 - 70%，并扰乱了搏动性。外源性游离脂肪酸抑制脂解和振荡幅度，可能是由于胞质长链辅酶 A（LC-CoA）增加所致。增加牛血清白蛋白百分比可增加刺激后的脂解和振荡幅度，可能是由于细胞内 LC-CoA 减少所致。这些数据首次表明了内源性脂解振荡，其依赖于葡萄糖并受游离脂肪酸调节。我们推测脂解振荡由振荡性葡萄糖代谢驱动，这导致 LC-CoA 对甘油三酯脂肪酶抑制作用的振荡性缓解。这些结果有助于理解脂解的生理和生化调节因子，如葡萄糖和游离脂肪酸。脂解振荡可能有利于将游离脂肪酸输送到肝脏、胰腺和其他组织。
