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 mol/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 ؎ A bnormal fat metabolism plays an important role in the pathogenesis of obesity-related type 2 diabetes (1-4), and elevated plasma free fatty acid (FFA) concentrations are associated with peripheral and hepatic insulin resistance (5-7). Adipose tissue is a dynamic organ that is vital to the regulation of glucose homeostasis, whole-body energy fuel regulation, feeding behavior, and body composition. It has previously been shown by Getty et al. (8), in dogs, that in the basal fasted state, FFA and glycerol oscillate in plasma with an average of nine pulses per hour and an average pulse duration of 5 min. It has also been shown that there is oscillatory lipolysis from the omentum with an average of 10 pulses per hour and an average pulse length of 6 min.Because lipolysis is primarily regulated by adrenergic modulation and insulin concentration, it is possible that either could be driving the plasma FFA oscillation. With the plasma insulin oscillation removed by the insulin clamp, FFAs still showed an oscillation in plasma, suggesting that insulin does not drive the FFA oscillation (8). The study also looked at the effect of ␤-adrenergic blockade. In three of the nine dogs studied, propranolol infusion seemed to suppress the FFA oscillation. In dogs where the FFA oscillation remained, propranolol infusion significantly disrupted the regularity of the plasma FFA oscillation (9,10). Further investigation of the role of the central nervous system in the regulation of in vivo lipolytic oscillations by Hucking et al. (11) suggested that lipolysis in the fasting state consisted of an oscillatory component dependent upon sympathetic innervation and a nonoscillatory component. In both above-mentioned studies, it is possible that lipolysis was still oscillating on the level of individual fat pads or even individual adipocytes and that these oscillations became unsynchronized and thus were lost, dampened, or below detection when sympathetic input was blocked.Thus, the present study determined whether the plasma FFA oscillation originates within the adipocyte from an internal pacemaker similar to that seen in the ␤-cell of the pancreas (12)(13)(14). The basal profiles of FFA, glycerol, and lactate release from isolated perifused adipocytes were determined in the basal state (Ϯ glucose), during stimulation of lipolysis with 1 mol/l isoproterenol (Ϯ glucose), during perifusion with increasing concentrations of oleate, and during perifusion with increasing percent BSA (ϩ isoproterenol). The results demonstrated that there were intrinsic lipolytic oscillations in adipocytes that were dependent on glucos...

Glucose-dependent insulinotropic polypeptide induces cytokine expression, lipolysis, and insulin resistance in human adipocytes

“…While the induction of glycerol release upon GIP was in line with previous reports (22,38), the low lipolytic response upon forskolin in our cell system was most probably related to our experimental design lacking albumin supplementation (2,21). Performing our experiments in the presence of albumin revealed a higher prolipolytic response upon forskolin and GIP.…”

Short-term effects of palmitate and 2-bromopalmitate on the lipolytic activity of rat adipocytes

“…The lipolytic response of fat cells was found to be attenuated at low albumin compared with results observed at higher protein content (Angel et al, 1971a;Cuchman et al, 1973;Vallano et al, 1983;Getty-Kaushik et al, 2005). In the presence of low albumin concentrations in the incubation medium, intracellular accumulation of fatty acids generated during lipolysis is higher, which leads to reduced lipolysis.…”

“…In the presence of low albumin concentrations in the incubation medium, intracellular accumulation of fatty acids generated during lipolysis is higher, which leads to reduced lipolysis. Conversely, at higher albumin concentrations, more fatty acids outs of the cell and the inhibitory action of endogenous fatty acids on lipolysis is decreased (Getty-Kaushik et al, 2005). Importantly, the effects of exogenous fatty acids on adipocytes are attenuated by high concentrations of albumin due to the binding of fatty acids to this protein (Cammisotto et al, 2003).…”

“…Fatty acids were also demonstrated to affect lipolysis. Interestingly, the presence of the lipolytic oscillations in adipose cells was discovered and the pivotal role in the regulation of these oscillations is ascribed to fatty acids (Getty-Kaushik et al, 2005). However, the regulatory role of fatty acids in lipolysis is not fully elucidated.…”

Regulation of lipolytic activity by long-chain acyl-coenzyme A in islets and adipocytes

“…Inhibition of FFA oxidation by malonyl-CoA may also contribute. Recent data support a major role for cytosolic LC-CoA in explaining the regulation of oscillatory lipolysis (13). The increased LC-CoA together with insulin inhibit adipocyte lipolysis.…”