OBJECTIVE Melanocortin-4 receptor (MC4R) and agouti-related peptide (AgRP) are involved in energy homeostasis in the rat. The aim of the present study was to evaluate the expression of MC4R and AgRP mRNAs in arcuate nucleus (ARC) during long term malnutrition of female ovariectomized rats. MATERIALS AND METHODS Ten female ovariectomized rats were divided into two equal groups (n=6) of normal ...

The understanding of the mechanisms whereby energy balance is regulated is essential to the unraveling of the pathophysiology of obesity. In the last three decades, focus was put on the metabolic role played by the hypothalamic neurons expressing proopiomelanocortin (POMC) and cocaine and amphetamine regulated transcript (CART) and the neurons co-localizing agouti-related peptide (AgRP), neurop...

The regulation of food intake in fish is a complex process carried out through several different mechanisms in the central nervous system (CNS) with hypothalamus being the main regulatory center. As in mammals, a complex hypothalamic circuit including two populations of neurons: one co-expressing neuropeptide Y (NPY) and Agouti-related peptide (AgRP) and the second one population co-expressing ...

Overexpression of the murine agouti gene results in obesity. The human homologue of agouti is expressed primarily in human adipocytes, and we have shown recombinant agouti protein to increase adipocyte intracellular Ca2+([Ca2+]i) and thereby stimulate lipogenesis. However, since recent data demonstrate that increasing adipocyte [Ca2+]i may also inhibit lipolysis, we have investigated the role o...

Agouti-related peptide (AgRP) neurons of the hypothalamus play a key role in regulating food intake and body weight, by releasing three different orexigenic molecules: AgRP; GABA; and neuropeptide Y. AgRP neurons express various G protein-coupled receptors (GPCRs) with different coupling properties, including Gs-linked GPCRs. At present, the potential role of Gs-coupled GPCRs in regulating the ...

Feeding provides substrate for energy metabolism, which is vital to the survival of every living animal and therefore is subject to intense regulation by brain homeostatic and hedonic systems. Over the last decade, our understanding of the circuits and molecules involved in this process has changed dramatically, in large part due to the availability of animal models with genetic lesions. In thi...

Activation of c-Jun N-terminal kinase 1 (JNK1)- and inhibitor of nuclear factor kappa-B kinase 2 (IKK2)-dependent signaling plays a crucial role in the development of obesity-associated insulin and leptin resistance not only in peripheral tissues but also in the CNS. Here, we demonstrate that constitutive JNK activation in agouti-related peptide (AgRP)-expressing neurons of the hypothalamus is ...

The cloning of mouse obesity genes and their human homologues provides unique opportunities to identify novel cellular targets for therapeutic intervention. The first of these to be cloned, agouti, antagonizes central nervous system melanocortin receptor (MCR) binding, resulting in hyperphagia and an obesity/hyperinsulinemia syndrome. There appears to be significant cross-talk between the agout...

The gastrointestinal peptide hormone ghrelin stimulates appetite in rodents and humans via hypothalamic actions. We discovered expression of ghrelin in a previously uncharacterized group of neurons adjacent to the third ventricle between the dorsal, ventral, paraventricular, and arcuate hypothalamic nuclei. These neurons send efferents onto key hypothalamic circuits, including those producing n...