Brandt Karsten, Arnold Myrtha, Geary Nori, Langhans Wolfgang, Leonhardt Monika
Institute of Animal Sciences, ETH Zurich, Schorenstrasse 16, 8603 Schwerzenbach, Switzerland.
Pharmacol Biochem Behav. 2006 Dec;85(4):722-7. doi: 10.1016/j.pbb.2006.11.002. Epub 2006 Dec 15.
This study investigated the effect of intraperitoneal (IP) injections of the fatty acid oxidation (FAO) inhibitor mercaptoacetate (MA, 45.6 mg/kg) on feeding in food-deprived rats. As previously, MA significantly stimulated feeding in ad libitum-fed rats. MA, however, reduced feeding in 18 and 36 h-fasted rats despite apparently antagonizing the fasting-induced increase in hepatic FAO. To test whether this anorectic effect involves beta-adrenergic stimulation, 36 h-fasted rats were IP injected with the nonspecific beta-adrenergic receptor antagonist propranolol (PROP, 0.5 mg/kg) just before MA injection. PROP attenuated MA's feeding-inhibitory effect, suggesting that MA anorexia is at least partially mediated by beta-adrenergic stimulation. Finally, we evaluated the role of subdiaphragmatic vagal afferent fibers in MA's feeding-inhibitory effect by testing the ability of MA to inhibit food intake in fasted rats after subdiaphragmatic vagal deafferentation (SDA). MA inhibited feeding similarly in SDA rats and sham-operated rats. These data demonstrate that subdiaphragmatic vagal afferents are not necessary for the feeding-inhibitory effect of peripheral MA. These results suggest that the FAO inhibitor MA elicits a feeding-inhibitory effect in fasted rats that is mediated by a different mechanism than its feeding-stimulatory effect.
本研究调查了腹腔注射脂肪酸氧化(FAO)抑制剂巯基乙酸盐(MA,45.6毫克/千克)对饥饿大鼠进食的影响。如前所述,MA显著刺激自由进食大鼠的进食。然而,MA却减少了禁食18小时和36小时大鼠的进食,尽管它明显拮抗了禁食诱导的肝脏FAO增加。为了测试这种厌食作用是否涉及β-肾上腺素能刺激,在注射MA之前,给禁食36小时的大鼠腹腔注射非特异性β-肾上腺素能受体拮抗剂普萘洛尔(PROP,0.5毫克/千克)。PROP减弱了MA的进食抑制作用,表明MA引起的厌食至少部分是由β-肾上腺素能刺激介导的。最后,我们通过测试MA抑制膈下迷走神经去传入(SDA)后禁食大鼠食物摄入的能力,评估膈下迷走神经传入纤维在MA进食抑制作用中的作用。MA对SDA大鼠和假手术大鼠的进食抑制作用相似。这些数据表明,膈下迷走神经传入对于外周MA的进食抑制作用并非必需。这些结果表明,FAO抑制剂MA在禁食大鼠中引发进食抑制作用,其介导机制与其进食刺激作用不同。