Mechanism for leptin resistance and obesity in ventromedial hypothalamus lesioned rats

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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peptides such as corticotropin releasing hormone (CRH) and cholecystokinin (CCK) is effective in the VMH-lesioned rats (unpublished).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.