Levin B E, Dunn-Meynell A A
Neurology Service, Department of Veterans Affairs Medical Center, East Orange 07018, USA.
Am J Physiol. 1997 May;272(5 Pt 2):R1365-70. doi: 10.1152/ajpregu.1997.272.5.R1365.
Neuropeptide Y (NPY) neurons in the hypothalamic arcuate nucleus (ARC) produce metabolic and physiological effects that promote the development and maintenance of obesity. In turn, NPY metabolism in these neurons is inhibited by dopamine release. In this study, ARC prepro-NPY mRNA and ARC/median eminence (ME) dopamine turnover were assessed in chow-fed male Sprague-Dawley rats prone to develop diet-induced obesity (DIO) or to be diet resistant (DR) when fed a high-energy (HE) diet. By in situ hybridization, DIO-prone rats had 39% more ARC NPY mRNA expression than DR-prone rats under chow-fed conditions. DIO-prone rat ARC/ME dopamine levels were 14% higher, but dopamine half-life was 176% longer and turnover was 59% less than DR-prone rats. Neither a 48-h fast nor 50% energy intake restriction for 5 days affected the already increased ARC NPY mRNA levels in DIO-prone rats. Both manipulations increased NPY expression to the level of DIO-prone rats in DR-prone rats by 23 and 35%, respectively. Finally, when fed HE diet for 2 wk, neither DIO- nor DR-prone rats altered their ARC NPY expression despite the development of obesity and hyperinsulinemia in DIO rats. Thus DIO-prone rats overexpress and fail to regulate ARC NPY mRNA to energy restriction or hyperinsulinemia. This dysregulation is possibly secondary to reduced inhibition because of defective ARC/ME dopamine turnover. Both may be important predisposing factors in the development of DIO.
下丘脑弓状核（ARC）中的神经肽Y（NPY）神经元会产生代谢和生理效应，促进肥胖的发展和维持。反过来，这些神经元中的NPY代谢会受到多巴胺释放的抑制。在本研究中，对喂食普通饲料的雄性斯普拉格-道利大鼠进行评估，这些大鼠在喂食高能（HE）饮食时容易发生饮食诱导性肥胖（DIO）或具有饮食抗性（DR）。通过原位杂交，在喂食普通饲料的条件下，易患DIO的大鼠ARC中NPY mRNA表达比易患DR的大鼠多39%。易患DIO的大鼠ARC/正中隆起（ME）多巴胺水平高14%，但多巴胺半衰期长176%，周转率比易患DR的大鼠低59%。48小时禁食或5天50%能量摄入限制均未影响易患DIO的大鼠中已经升高的ARC NPY mRNA水平。这两种处理分别使易患DR的大鼠的NPY表达增加到易患DIO的大鼠水平的23%和35%。最后，当喂食HE饮食2周时，尽管DIO大鼠出现了肥胖和高胰岛素血症，但易患DIO和DR的大鼠均未改变其ARC NPY表达。因此，易患DIO的大鼠过度表达ARC NPY mRNA，并且无法根据能量限制或高胰岛素血症对其进行调节。这种失调可能是由于ARC/ME多巴胺周转率缺陷导致抑制作用降低所致。两者可能都是DIO发生发展的重要易感因素。
