Pseudorabies virus (PRV)-614 was injected into the tracheal wall of male MC4R-GFP transgenic mice, resulting in retrograde infections in spinal cord and autonomic premotor areas of the brain including the rostroventrolateral medulla (RVLM). This polysynaptic pathway to the airway may form the substrate underlying the impact of IML and RVLM on airway function. The neurochemical phenotype of MC4R...

This study was designed to assess whether MC4R signaling existed in vestibular nuclei modulated the activity of kidney by a virally mediated transsynaptic tracing study. Pseudorabies virus (PRV)-614 was injected into the kidney in adult male MC4R-green fluorescent protein (GFP) transgenic mice (n = 5). After a survival time of 5 days, the mice were assigned to humanely sacrifice, and the brains...

Bioactive peptides derived from the prohormone, pro-opiomelanocortin (POMC), are generated in neurons of the hypothalamus and act as endogenous ligands for the melanocortin-4 receptor (MC4R), a key molecule underlying appetite control and energy homeostasis. It is therefore important to understand many aspects of POMC gene regulation in the brain, as pharmacological manipulation of POMC express...

Many attempts have been made to find novel therapeutic strategies for non-alcoholic steatohepatitis (NASH), while their clinical efficacy is unclear. We have recently reported a novel rodent model of NASH using melanocortin 4 receptor-deficient (MC4R-KO) mice, which exhibit the sequence of events that comprise hepatic steatosis, liver fibrosis, and hepatocellular carcinoma with obesity-related ...

We assessed the efficacy of simultaneous agonism at the glucagon-like peptide-1 receptor (GLP-1R) and the melanocortin-4 receptor (MC4R) for the treatment of obesity and diabetes in rodents. Diet-induced obese (DIO) mice were chronically treated with either the long-acting GLP-1R agonist liraglutide, the MC4R agonist RM-493 or a combination of RM-493 and liraglutide. Co-treatment of DIO mice wi...

Thirteen genes were mapped to the porcine genome by using either linkage mapping of the PiGMaP families (eight genes) or typing of a porcine somatic cell hybrid panel (12 genes). The genes were chosen from interesting locations in the human genome. The physical gene assignments to pig chromosomes (SSC) with corresponding human chromosome (HSA) locations include the following: FGF7 (HSA15), MADH...

The effects of chronic stress and glucocorticoids receptor antagonist (RU486) on expression of melanocortin 4 receptor (MC4R) mRNA in arcuate nucleus (ARC) of male rats were evaluated. In this study, adult male Sprague Dawley rats were placed into four groups (n=6/group); stress, RU486, stress/RU486, and control groups. In stress group, the rats were restrained, 1 h/day, for 12 days. In RU486 g...

Agouti-related protein (AGRP) is an endogenous antagonist of melanocortin action that functions in the hypothalamic control of feeding behavior. Although previous studies have shown that AGRP binds three of the five known subtypes of melanocortin receptor, the receptor domains participating in binding and the molecular interactions involved are presently unknown. The present studies were design...

To examine if brain neurons involved in the efferent control of the kidneys possess melanocortin-4 receptor (MC4-R) and/or tryptophan hydroxylase (TPH). Retrograde tracing pseudorabies virus (PRV)-614 was injected into the kidneys in adult male MC4R-green fluorescent protein (GFP) transgenic mice. After a survival time of 3-7 days, spinal cord and brain were removed and sectioned, and processed...

Activation of central melanocortin receptors (MCR) inhibits fever, but the identity of the MCR subtype(s) mediating this antipyretic effect is unknown. To determine whether selective central melanocortin receptor-4 (MC4R) activation produces antipyretic effects, the MC4R selective agonist MRLOB-0001 (CO-His-d-Phe-Arg-Trp-Dab-NH(2)) was administered intracerebroventricularly to rats treated with...