Hypothalamic Neuropeptides and Appetite Response in Anorexia-Cachexia Animal

Abstract

CACHEXIA, characterized by anorexia and marked weight loss, is a complex syndrome in patients with inflammatory disease and cancer. In particular, the pathogenesis of cancer cachexia is a multifactor syndrome that includes reduced food intake, alteration in energy and substrate metabolism in the host and accelerated fat and muscle loss [1]. As anorexia-cachexia syndrome compromises the quality of life and contributes to mortality in patients, it is important to examine the essential mechanisms of the syndrome in order to develop effective therapeutics even though anorexiacachexia syndrome may be caused by multiple factors.In this review, we focus on the hypothalamic neuropeptide gene expression in an anorexia-cachexia animal model because neuropeptides in the hypothalamus may be the key molecules that regulate the appetite and feeding behavior in cancer anorexia-cachexia syndrome [2] as well as in normal conditions [3,4]. Quantitative changes in neuropeptides gene expressions in the hypothalamus and the relevance of their changes in abnormal nutritional conditions (e.g., negative energy balance) are reviewed and discussed by a comparison of three different types of anorexia and anorexia-cachexia animal models; dehydration-induced anorexia, bacterial lipopolysaccharide (LPS)-induced anorexia, and cancer-induced anorexia-cachexia syndrome. Hypothalamic neuropeptides related to appetite and feeding behaviorsIt is well established that appetite and feeding behaviors are primarily controlled by a feeding center, the lateral hypothalamic area (LHA), and a satiety center, the ventromedial hypothalamic nucleus (VMH), in the hypothalamus [5]. Recently, neural networks and chemical mediators among the hypothalamic nucleinot only the LHA and the VMH but also the arcuate nucleus (Arc) and the paraventricular nucleus (PVN)-related to feeding regulation have been studied by many investigators. Various kinds of neuropeptides as well as classic neurotransmitters such as dopamine and serotonin act as feeding regulatory factors in the neural networks at these sites [6].For example, centrally administered neuropeptide Y (NPY) strongly stimulates feeding in mice and rats [7]. Many studies have demonstrated that the expression of the NPY gene was markedly increased in the neurons of the Arc after food deprivation (starvation). This type of peptide is called an "orexigenic" neuropeptide. Orexins/hypocretins, which are produced in the neurons located in the LHA [5], are also potent orexigenic neuropeptides. On the other hand, proopiomelanocortin (POMC), which encodes α melanocyte-stimulating

Anorexia in human and experimental animal models: physiological aspects related to neuropeptides

“…Because pathophysiological models of anorexia may involve multiple factors as previously described, developing a simple method to induce anorexia in animal models is necessary in order to improve our understanding of the neuronal and molecular mechanisms responsible for anorexia [16]. To resolve this problem, several groups have proposed the use of dehydration-induced anorexia in animal models [10,[89][90][91].…”

“…Previous studies have demonstrated that cytokines and hypothalamic neuropeptides are involved in cancer cachexia-anorexia syndrome [110][111][112], and that cachectic factors such as cytokines mimic the effects of leptin on the hypothalamus and induce anorexia in cachexia-anorexia syndrome [16].…”

“…From the point of view of hypothalamic neuropeptides, distinct patterns of the orexigenic or anorexigenic neuropeptides are seen among these anorexia models. For example, dehydration-induced anorexia primarily causes up-regulation of the hypothalamic anorexigenic peptides, whereas LPS-induced anorexia causes down-regulation of orexigenic peptides in addition to the up-regulation of the anorexigenic peptides [16].…”

Pathophysiology and Treatment Options for Cardiac Anorexia

“…The assumption of increased LPS-challenge in patients affected with CHF is supported by further studies [66][67][68]. In animal models, LPS has been shown to be a strong inducer of inflammation and anorexia [24,69]. Cytokine-induced anorexia in acute as well as chronic diseases can be explained through central and peripheral pathomechanisms [70].…”

A role of nesfatin-1/NucB2 in dehydration-induced anorexia

“…Because pathological models of anorexia may involve multiple factors, it is necessary to develop a simple method to induce anorexia in animal models to improve our understanding of the neuronal and molecular mechanisms responsible for anorexia (21). To resolve this problem, several groups have proposed the use of dehydration-induced anorexia in animal models (18,24,25).…”