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Setmelanotide

About: Setmelanotide is a research topic. Over the lifetime, 30 publications have been published within this topic receiving 10241 citations. The topic is also known as: BIM-22493 & RM-493.

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Journal ArticleDOI
10 Jan 1997-Cell
TL;DR: The data identify a novel signaling pathway in the mouse for body weight regulation and support a model in which the primary mechanism by which agouti induces obesity is chronic antagonism of the MC4-R.

2,979 citations

Journal ArticleDOI
26 Jun 1997-Nature
TL;DR: The severe obesity found in two severely obese children who are members of the same highly consanguineous pedigree provides the first genetic evidence that leptin is an important regulator of energy balance in humans.
Abstract: The extreme obesity of the obese (ob/ob) mouse is attributable to mutations in the gene encoding leptin, an adipocyte-specific secreted protein which has profound effects on appetite and energy expenditure We know of no equivalent evidence regarding leptin's role in the control of fat mass in humans We have examined two severely obese children who are members of the same highly consanguineous pedigree Their serum leptin levels were very low despite their markedly elevated fat mass and, in both, a homozygous frame-shift mutation involving the deletion of a single guanine nucleotide in codon 133 of the gene for leptin was found The severe obesity found in these congenitally leptin-deficient subjects provides the first genetic evidence that leptin is an important regulator of energy balance in humans

2,912 citations

Journal ArticleDOI
26 Mar 1998-Nature
TL;DR: A homozygous mutation in the human leptin receptor gene results in a truncated leptin receptor lacking both the transmembrane and the intracellular domains, which indicates that leptin is an important physiological regulator of several endocrine functions in humans.
Abstract: The adipocyte-specific hormone leptin, the product of the obese (ob) gene, regulates adipose-tissue mass through hypothalamic effects on satiety and energy expenditure Leptin acts through the leptin receptor, a single-transmembrane-domain receptor of the cytokine-receptor family In rodents, homozygous mutations in genes encoding leptin or the leptin receptor cause early-onset morbid obesity, hyperphagia and reduced energy expenditure These rodents also show hypercortisolaemia, alterations in glucose homeostasis, dyslipidaemia, and infertility due to hypogonadotropic hypogonadisms In humans, leptin deficiency due to a mutation in the leptin gene is associated with early-onset obesity Here we describe a homozygous mutation in the human leptin receptor gene that results in a truncated leptin receptor lacking both the transmembrane and the intracellular domains In addition to their early-onset morbid obesity, patients homozygous for this mutation have no pubertal development and their secretion of growth hormone and thyrotropin is reduced These results indicate that leptin is an important physiological regulator of several endocrine functions in humans

2,291 citations

Journal ArticleDOI
TL;DR: In this paper, the nucleotide sequence of the MC4R gene in 500 children with severe childhood obesity was determined, and the results were correlated with the signaling properties of mutant receptors.
Abstract: Background Melanocortin 4 receptor (MC4R) deficiency is the commonest monogenic form of obesity. However, the clinical spectrum and mode of inheritance have not been defined, pathophysiological mechanisms leading to obesity are poorly understood, and there is little information regarding genotype–phenotype correlations. Methods We determined the nucleotide sequence of the MC4R gene in 500 probands with severe childhood obesity. Family studies were undertaken to examine cosegregation of identified mutations with obesity. Subjects with MC4R deficiency underwent metabolic and endocrine evaluation; the results were correlated with the signaling properties of mutant receptors. Results Twenty-nine probands (5.8 percent) had mutations in MC4R; 23 were heterozygous, and 6 were homozygous. Mutation carriers had severe obesity, increased lean mass, increased linear growth, hyperphagia, and severe hyperinsulinemia; homozygotes were more severely affected than heterozygotes. Subjects with mutations retaining residual...

1,518 citations

Journal ArticleDOI
TL;DR: Patients with rare defects in the gene encoding proopiomelanocortin have extreme early-onset obesity, hyperphagia, hypopigmentation, and hypocortisolism and are treated with setmelanotide, a new melanocortIn-4 receptor agonist, which had a sustainable reduction in hunger and substantial weight loss.
Abstract: Patients with rare defects in the gene encoding proopiomelanocortin (POMC) have extreme early-onset obesity, hyperphagia, hypopigmentation, and hypocortisolism, resulting from the lack of the proopiomelanocortin-derived peptides melanocyte-stimulating hormone and corticotropin. In such patients, adrenal insufficiency must be treated with hydrocortisone early in life. No effective pharmacologic treatments have been available for the hyperphagia and obesity that characterize the condition. In this investigator-initiated, open-label study, two patients with proopiomelanocortin deficiency were treated with setmelanotide, a new melanocortin-4 receptor agonist. The patients had a sustainable reduction in hunger and substantial weight loss (51.0 kg after 42 weeks in Patient 1 and 20.5 kg after 12 weeks in Patient 2).

331 citations

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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20216
20207
20193
20184
20171
20164