Zalatan F, Krause J A, Blask D E
Laboratory of Experimental Neuroendocrinology/Oncology, Bassett Research Institute, Cooperstown, New York 13326, USA.
Endocrinology. 2001 Sep;142(9):3783-90. doi: 10.1210/endo.142.9.8378.
Because the pineal hormone melatonin has been implicated in affecting adiposity in rats and fatty acid transport in certain rat tumor models, we tested whether melatonin regulates lipolysis in a normal cell system in vitro. Adipocytes were isolated from the inguinal fat pads (i.e. sc fat) of Sprague Dawley male rats during mid-light phase. Lipolysis was stimulated with isoproterenol (3 microM), and cells were incubated for 4 h in the presence or absence of a physiological circulating concentration of melatonin (1 nM). Lipolysis was measured by determining the amount of glycerol present in the incubation buffer, expressed as nmol glycerol/mg cellular fatty acid. We observed a 20- to 30-fold stimulation of basal lipolysis by isoproterenol, and this stimulation was inhibited 50--70% by melatonin. Melatonin exhibited this effect over a wide range of concentrations tested (100 pM-1 microM) with an IC(50) of approximately 500 pM. The effect by melatonin (1 nM) was completely blocked by pertussis toxin (50 ng/ml), by 8-bromo-cAMP (10 nM), and by the melatonin receptor antagonist S-20928 (1 nM). These results suggest that the antilipolytic effect occurs through one of the G(i) protein-coupled melatonin receptors because we have shown that both the mt(1) (Mel 1a) and MT(2) (Mel 1b) melatonin receptors are expressed in inguinal adipocytes. Melatonin inhibition of lipolysis was not observed in adipocytes isolated from rat epididymal fat pads (i.e. visceral fat), even though these cells also express both the mt(1) and MT(2) receptors. The results indicate that physiological circulating concentrations of melatonin inhibit isoproterenol-induced lipolysis in rat adipocytes via a G protein-coupled melatonin receptor-mediated signal transduction pathway in a site-specific manner.
由于松果体激素褪黑素被认为与影响大鼠肥胖及某些大鼠肿瘤模型中的脂肪酸转运有关，我们测试了褪黑素在体外正常细胞系统中是否调节脂肪分解。在光照中期从Sprague Dawley雄性大鼠的腹股沟脂肪垫（即皮下脂肪）分离脂肪细胞。用异丙肾上腺素（3μM）刺激脂肪分解，细胞在有或无生理循环浓度褪黑素（1 nM）的情况下孵育4小时。通过测定孵育缓冲液中甘油的含量来测量脂肪分解，以nmol甘油/ mg细胞脂肪酸表示。我们观察到异丙肾上腺素对基础脂肪分解有20至30倍的刺激作用，而这种刺激被褪黑素抑制了50 - 70％。褪黑素在广泛的测试浓度范围（100 pM - 1μM）内表现出这种作用，IC（50）约为500 pM。褪黑素（1 nM）的作用被百日咳毒素（50 ng / ml）、8 - 溴 - cAMP（10 nM）和褪黑素受体拮抗剂S - 20928（1 nM）完全阻断。这些结果表明，抗脂解作用是通过一种G（i）蛋白偶联的褪黑素受体发生的，因为我们已经表明mt（1）（Mel 1a）和MT（2）（Mel 1b）褪黑素受体都在腹股沟脂肪细胞中表达。在从大鼠附睾脂肪垫（即内脏脂肪）分离的脂肪细胞中未观察到褪黑素对脂肪分解的抑制作用，尽管这些细胞也表达mt（1）和MT（2）受体。结果表明，生理循环浓度的褪黑素通过G蛋白偶联的褪黑素受体介导的信号转导途径以位点特异性方式抑制大鼠脂肪细胞中异丙肾上腺素诱导的脂肪分解。
