Leptin-induced lipolysis opposes the tonic inhibition of endogenous adenosine in white adipocytes

The aim of the present study was to gain insight into the signaling pathway used by leptin to stimulate lipolysis. The lipolytic rate of white adipocytes from sex- and age-matched lean (+/+) and fa/fa rats was determined in the absence or presence of leptin together with a number of agents acting at different levels of the signaling cascade. Leptin did not modify FSK-, dbcAMP-, and IBMX-stimulated lipolysis. Lipolysis can also be maximally stimulated by lowering media adenosine levels with adenosine deaminase (ADA), i.e., in the ligand-free state. Although ADA produced near maximal lipolysis in adipocytes of lean animals, only half of the maximal lipolytic rate (50.9+/-3.2%) was achieved in fat cells from fa/fa rats (P=0.0034). In adipocytes from lean animals preincubated with ADA, leptin caused a concentration-related stimulation of lipolysis (P=0.0001). However, leptin had no effect on the lipolytic activity of adipocytes in the ligand-free state from fa/fa rats. The adenosine A1 receptor agonist CPA effectively inhibited basal lipolysis in both lean and obese adipocytes (P=0.0001 and P=0.0090, respectively). Leptin had no effect on the lipolytic rate of adipocytes isolated from fa/fa rats and preincubated with CPA. When adipocytes were incubated with the A1 receptor antagonist DPCPX, a significant increase in glycerol release was observed in fa/fa fat cells (P=0.009), whereas cells isolated from lean rats showed no differences to ADA-stimulated lipolysis. After pretreatment with PTX, which inactivates receptor-mediated Gi function, adipocytes of obese rats became as responsive to the stimulatory actions of ISO as cells from lean rats (P=0.0090 vs. ISO in fa/fa rats; P=0.2416 vs. lean rats, respectively). PTX treatment of lean cells, however, did not alter their response to this lipolytic agent. It can be concluded that the lipolytic effect of leptin is located at the adenylate cyclase/Gi proteins level and that leptin-induced lipolysis opposes the tonic inhibition of endogenous adenosine in white adipocytes

Law defining the critical level of driver fatigue in terms of hours without sleep: Criminal justice professionals\u27 opinions and fatal accident data

The aims of the present study were to determine the support among criminal justice professionals for a law that defines the critical limit of driver fatigue in terms of 24 consecutive hours of wakefulness; and to determine how many drivers causing fatal accidents would be potentially covered by such a law. The data included an online questionnaire data collected from 325 criminal justice professionals (96 prosecutors, 129 traffic police officers, and 100 local police officers with experience in traffic surveillance and accident investigations) and the national database of fatal road accidents studied in depth (N = 1871; 2002-2008). The support for such a law was quite low among prosecutors while police officers were more in favor than against it. Only a handful of the (survived) drivers who caused a fatal accident were awake for more than 24 consecutive hours. We discuss several challenges and considerations associated with such a law