Li Ai-Jun, Dinh Thu T, Ritter Sue
Washington State University, Pullman, WA 99164-6520, USA.
Peptides. 2008 Oct;29(10):1732-9. doi: 10.1016/j.peptides.2008.05.026. Epub 2008 Jun 5.
Neuropeptide Y (NPY) conjugated with a ribosomal inactivating toxin, saporin (SAP), is a toxin that targets NPY receptor-expressing cells. Injection of NPY-SAP into the rat arcuate nucleus (Arc) and basomedial hypothalamus (BMH) destroys two populations of NPY-receptor-expressing neurons important for the control of food intake and body weight, NPY and pro-opiomelanocortin (POMC) and cocaine and amphetamine related transcript (CART) neurons, and produces profound hyperphagia and obesity. Here, we investigated the contribution of lateral hypothalamus (LHA) orexigenic peptides, orexins and melanocortin concentrating hormone (MCH), to these lesion effects. We microinjected NPY-SAP into two sites on each side of the Arc, causing a loss of NPY and POMC/CART neurons that was limited to the Arc. Lesioned rats rapidly became hyperphagic and obese. However, MCH and prepro-orexin mRNA expression were not increased in the LHA in the lesioned rats, but were decreased at some levels of the LHA or were unchanged. NPY-SAP-induced obesity therefore differs from dietary obesity and from obesity associated with leptin or leptin receptor deficiency in which MCH gene expression is increased. The Arc NPY-SAP lesion produces obesity and hyperphagia that does not require overexpression of hypothalamic neuropeptides currently considered to provide major stimulatory drive for food intake: NPY, agouti gene-related protein, MCH or orexins. The source of the seemingly unregulated stimulatory drive for feeding in these animals has not been identified, but may be associated with hindbrain or endocrine mechanisms.
与核糖体失活毒素皂草素（SAP）结合的神经肽Y（NPY）是一种靶向表达NPY受体细胞的毒素。向大鼠弓状核（Arc）和下丘脑基底内侧（BMH）注射NPY-SAP会破坏两组对食物摄入和体重控制至关重要的表达NPY受体的神经元，即NPY和阿片促黑素皮质素原（POMC）以及可卡因和苯丙胺调节转录肽（CART）神经元，并导致严重的食欲亢进和肥胖。在此，我们研究了下丘脑外侧区（LHA）的促食欲肽——食欲素和促黑素聚集激素（MCH）对这些损伤效应的作用。我们将NPY-SAP微量注射到Arc两侧的两个位点，导致仅限于Arc的NPY和POMC/CART神经元丧失。损伤的大鼠迅速变得食欲亢进和肥胖。然而，损伤大鼠LHA中的MCH和前食欲素原mRNA表达并未增加，而是在LHA的某些水平下降或未发生变化。因此，NPY-SAP诱导的肥胖不同于饮食性肥胖以及与瘦素或瘦素受体缺乏相关的肥胖，在后两种肥胖中MCH基因表达会增加。Arc NPY-SAP损伤导致的肥胖和食欲亢进并不需要目前认为为食物摄入提供主要刺激驱动力的下丘脑神经肽过度表达：NPY、刺鼠基因相关蛋白、MCH或食欲素。这些动物中看似不受调节的进食刺激驱动力来源尚未确定，但可能与后脑或内分泌机制有关。
