Melanocortin 4 receptors (MC4Rs) in the central nervous system are key regulators of energy and glucose homeostasis. Notably, obese patients with MC4R mutations are hyperinsulinemic and resistant to obesity-induced hypertension. Although these effects are probably dependent upon the activity of the autonomic nervous system, the cellular effects of MC4Rs on parasympathetic and sympathetic neuron...

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...

BACKGROUND Several studies have reported that carriers of the 103I allele of the melanocortin-4 receptor (MC4R) gene had lower body weight than did persons with the wild-type genotype. A recent study found an association of the MC4R 103I variant with carbohydrate intake, which may mediate some of the association of this variant with leanness. OBJECTIVE The purpose of the study was to investig...

Phan, Loan K., Wendy K. Chung, and Rudolph L. Leibel. The mahoganoid mutation (Mgrn1) improves insulin sensitivity in mice with mutations in the melanocortin signaling pathway independently of effects on adiposity. Am J Physiol Endocrinol Metab 291: E611–E620, 2006. First published April 25, 2006; doi:10.1152/ajpendo.00034.2006.—Mahoganoid (Mgrn1) is a mutation of the mahogunin (Mgrn1) gene. Th...

Mutations in the Melanocortin 4 receptor are implicated in 1-6% of early onset or severe adult obesity cases. Most of the patients carry heterozygous missense mutations. Arguments for the pathogenicity of these mutations are based on the frequency of rare functionally relevant non-synonymous mutations in severely obese children and adults versus non-obese controls, the segregation of mutations ...

BACKGROUND AND OBJECTIVES MC4R (melanocortin-4 receptor) gene polymorphisms have been associated with serum triglycerides (TG) in Caucasians and Japanese, but no reports are available Chinese. The purpose of this study was to find whether there was an association of rs17782313 polymorphisms at the MC4R gene with serum TG in elderly Chinese. METHODS AND STUDY DESIGN 2,012 over 40 years partici...

Chronic use of morphine is accompanied by the development of morphine tolerance, which is one of the major problems associated with opiate treatment. Experimental evidence indicates that melanocortin 4 receptor (MC4R) is involved in development of morphine tolerance. Therefore, we investigated the influence of repeated intrathecal injection of a MC4R antagonist (HS014) on the development of mor...

The 78 kDa glucose-regulated protein (GRP78) is an endoplasmic reticulum (ER)-resident molecular chaperone. GRP78 a member of the 70 heat shock family proteins involved in correcting and clearing misfolded ER. In response to cellular stress, escapes from ER moves plasma membrane where it (a) functions as receptor for many ligands, (b) behaves autoantigen autoantibodies that contribute human dis...