Mutations in ligands and receptors of the leptin–melanocortin pathway that lead to obesity

@article{Farooqi2008MutationsIL,
  title={Mutations in ligands and receptors of the leptin–melanocortin pathway that lead to obesity},
  author={I. Sadaf Farooqi and Stephen O’Rahilly},
  journal={Nature Clinical Practice Endocrinology \&Metabolism},
  year={2008},
  volume={4},
  pages={569-577}
}
Obesity is associated with increased morbidity and mortality from cardiovascular disease, diabetes mellitus and certain cancers. The prevalence of obesity is increasing rapidly throughout the world and is now recognized as a major global public-health concern. Although the increased prevalence of obesity is undoubtedly driven by environmental factors, the evidence that inherited factors profoundly influence human fat mass is equally compelling. Twin and adoption studies indicate that up to 70… 
The genetics of obesity: the role of the melanocortin 4 receptor
TLDR
Polymorphisms within the gene encoding for the melanocortin-4 receptor (MC4R), a hypothalamic receptor with the primary function of regulating food intake, are a significant cause of severe human obesity.
Leptin-melanocortin system, body weight regulation and obesity.
TLDR
Therapy with human recombinant leptin in patients with genetic deficiency of thehormone is an effective medical treatment of obesity, although only applicable to very fewfamilies.
Neural melanocortin receptors in obesity and related metabolic disorders.
www.ssoar.info From monogenic to polygenic obesity: recent advances
TLDR
The identification of inborn deficiency of the mostly adipocytederived satiety hormone leptin in extremely obese children from consanguineous families paved the way to the first pharmacological therapy for obesity based on a molecular genetic finding.
Molecular Basis of Obesity: Current Status and Future Prospects
TLDR
It is evidence that obesity is a strongly heritable disorder, and an update on the molecular basis of obesity is provided, to help to characterize disease mechanisms, provide new targets for drug design, and lead to an early diagnosis, treatment, and prevention of obesity.
Hypothalamic Inflammation: Marker or Mechanism of Obesity Pathogenesis?
TLDR
An overview of energy homeostasis—the biological process that underlies the control of body fat mass—is presented and evidence that defects in this regulatory system contribute to obesity pathogenesis is described.
From monogenic to polygenic obesity: recent advances
TLDR
The identification of inborn deficiency of the mostly adipocyte-derived satiety hormone leptin in extremely obese children from consanguineous families paved the way to the first pharmacological therapy for obesity based on a molecular genetic finding.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 71 REFERENCES
The Central Melanocortin System and Energy Homeostasis
  • R. Cone
  • Biology, Medicine
    Trends in Endocrinology & Metabolism
  • 1999
Melanocortin-4 receptor mutations are a frequent and heterogeneous cause of morbid obesity.
TLDR
It is demonstrated that MC4-R mutations are a frequent but heterogeneous genetic cause of morbid obesity and transmission in the families of the carriers indicates a variable expressivity that is not related to the functional severity of the mutations.
Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene.
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
A unique metabolic syndrome causes obesity in the melanocortin-3 receptor-deficient mouse.
TLDR
To assess the role of the MC3-R in energy homeostasis, the majority of themc3r coding sequence was deleted from the mouse genome and found that homozygous null mc3r mice exhibit an exclusively metabolic syndrome.
Phenotypic effects of leptin replacement on morbid obesity, diabetes mellitus, hypogonadism, and behavior in leptin-deficient adults.
TLDR
Leptin replacement therapy in leptin-deficient adults with established morbid obesity results in profound weight loss, increased physical activity, changes in endocrine function and metabolism, including resolution of type 2 diabetes mellitus and hypogonadism, and beneficial effects on ingestive and noningestive behavior.
A Unique Metalolic Sysdrone Causes Obesity in the Melanocortin-3 Receptor-Deficient Mouse.
TLDR
To assess the role of the MC3-R in energy homeostasis, the majority of themc3r coding sequence was deleted from the mouse genome and found that homozygous null mc3r mice exhibit an exclusively metabolic syndrome.
Clinical and molecular genetic spectrum of congenital deficiency of the leptin receptor.
TLDR
The prevalence of pathogenic LEPR mutations in a cohort of subjects with severe, early-onset obesity was 3%.
Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency.
The wide range of phenotypic abnormalities seen in the leptin-deficient ob/ob mouse and their reversibility by leptin administration provide compelling evidence for the existence of multiple
Prevalence of Melanocortin-4 Receptor Deficiency in Europeans and Their Age-Dependent Penetrance in Multigenerational Pedigrees
TLDR
A robust estimate of age-related penetrance for MC4R deficiency is established and a generational effect on penetrance is demonstrated, which may relate to the development of an “obesogenic” environment.
Mutations in the human melanocortin-4 receptor gene associated with severe familial obesity disrupts receptor function through multiple molecular mechanisms.
TLDR
It is established that defective expression on the cell surface is a common mechanism impairing receptor function and a potentially novel molecular mechanism of receptor dysfunction whereby a mutation alters the relative affinities of a receptor for its natural agonist versus antagonist is identified.
...
1
2
3
4
5
...