The melanocortin system is composed of the melanocortin peptides, adrenocorticotropic hormone and alpha-, beta-, and gamma-melanocyte-stimulating hormone, the melanocortin receptors (MCRs), and the endogenous antagonists agouti- and agouti-related protein. Melanocortin peptides exert multiple effects upon the host, including anti-inflammatory and immunomodulatory effects. Leukocytes are a sourc...

Agouti is a secreted paracrine factor that regulates pigmentation in hair follicle melanocytes. Several dominant mutations cause ectopic expression of agouti, resulting in a phenotype characterized by yellow fur, adult-onset obesity and diabetes, increased linear growth and skeletal mass, and increased susceptibility to tumors. Humans also produce agouti protein, but the highest levels of agout...

The hypothalamus is critical for feeding and body weight regulation. Prevailing studies focus on hypothalamic neurons that are defined by selectively expressing transcription factors or neuropeptides including those expressing proopiomelanocortin (POMC) and agouti-related peptides (AgRP). The Cre expression driven by the pancreas-duodenum homeobox 1 promoter is abundant in several hypothalamic ...

The importance of the central melanocortin system in the regulation of energy balance is highlighted by studies in transgenic animals and humans with defects in this system. Mice that are engineered to be deficient for the melanocortin-4 receptor (MC4R) or pro-opiomelanocortin (POMC) and those that overexpress agouti or agouti-related protein (AgRP) all have a characteristic obese phenotype typ...

Leptin has beneficial effects on glucose metabolism via actions in the hypothalamus, but the roles of specific subgroups of neurons responsible for these antidiabetic effects remain unresolved. We generated diabetic Lep(ob/ob) or Lepr(db/db) mice lacking or re-expressing leptin receptors (LepRb) in subgroups of neurons to explore their contributions to leptin's glucose-lowering actions. We show...

Melanocortin- 4 receptor (MC4R) and agouti- related peptide (AgRP) are involved in energy homeostasis in rats. According to MC4R and AgRP effects on luteinizing hormone (LH) secretion, they may influence the estrous cycle of rats. Therefore, the aim of this study was to investigate the expression of MC4R and AgRP mRNAs at different stages of estrous cycle in the rat's hypothalamus. The estrous ...

OBJECTIVE Melanocyte-stimulating hormone (MSH) peptides processed from proopiomelanocortin (POMC) regulate energy homeostasis by activating neuronal melanocortin receptor (MC-R) signaling. Agouti-related peptide (AgRP) is a naturally occurring MC-R antagonist but also displays inverse agonism at constitutively active melanocortin-4 receptor (MC4-R) expressed on transfected cells. We investigate...

HE action of genes at the agouti locus, in combination with “wild” genes at other color loci, results in coat color phenotypes which range from all black ( a / a ) to all yellow (Ay / ) . Between these two extremes is the agouti phenotype (A/--) which is typically characterized by the presence of a subapical yellow band on an otherwise black hair. These observations indicate that alleles at the...

The signaling systems underlying eating behavior control are complex. The current review focuses on gastrointestinal (GI) signaling systems as physiological key functions for metabolic control. Many of the peptides that are involved in the regulation of food intake in the brain are also found in the enteric nervous system and enteroendocrine cells of the mucosa of the GI tract. The only identif...