Mechanism for leptin resistance and obesity in ventromedial hypothalamus lesioned rats

下丘脑腹内侧（VMH）一直被认为是一个饱腹感中心，因为下丘脑腹内侧的病变会导致贪食和肥胖。最近，抑制食物摄入的瘦素在vmh损伤大鼠（瘦素抵抗）中不能发挥其作用。我们推测，在VMH损伤后，产生食欲素或三聚氰胺细胞浓缩激素（MCH）等致氧肽的致氧神经元可能会增加其活性。否则，由于VMH中存在黑素皮质素受体，VMH病变可能使受体耗损，导致瘦素抵抗，对α-促黑素细胞激素（MSH）等厌食性肽无反应。我们的研究结果表明，VMH损伤大鼠下丘脑外侧的促食素和MCH含量降低，表明这些促食神经元的活性可能在VMH损伤后受到抑制。这些研究结果分别发表在《神经内分泌学杂志》2002年第15期51-60期和2003年第16期79-83期。此外，MSH以及其他厌食症肽如促肾上腺皮质激素释放激素（CRH）和胆囊收缩素（CCK）对vmh损伤大鼠有效（未发表）。因此，贪食和瘦素抵抗既不是由于产生食欲素或MCH的厌氧神经元的过度活跃，也不是由于对MSH、CRH或CCK等厌食肽的无反应。我们正在进行实验，以证明一个新的假设，而不是VMH是一个饱腹感中心。

The ventromedial hypothalamus (VMH) has long been known as a satiety center because the lesion of the VMH results in hyperphagia and obesity. Recently leptin that inhibits food intake, can not exert its effect in VMH-lesioned rats (leptin resistance). We hypothesize that orexigenic neurons which produce orexigenic peptides such as orexin or melamocyte-concentrating hormone (MCH) may increase their activity after VMH lesion. Otherwise, since there is melanocortin receptor in the VMH, VMH lesion may deplete the receptor, resulting in leptin resistance and unresponsiveness to anorexic peptide such as α-melanocyte stimulating hormone (MSH). Our results show that orexin and MCH contents in the lateral hypothalamus are decreased in the VMH-lesioned rats suggesting that these orexigenic neurons may be inhibited their activity after VMH lesion. These results are published in the Journal of Neruoendocrinology 15, 51-60, 2002 and 16, 79-83, 2003. In addition, MSH as well as other anorexia peptides such as corticotropin releasing hormone (CRH) and cholecystokinin (CCK) is effective in the VMH-lesioned rats (unpublished). Thus the hyperphagia and leptin resistance is neither due to the hyperactivity of orexigenic neurons that produce orexin or MCH nor unresponsiveness to anorexia peptides such as MSH, CRH or CCK. We are conducting experiments to testify a new hypothesis in stead of that the VMH is a satiety center.