Fifty-one unrelated probands with early onset severe obesity (body mass index (BMI) > 99th percentile; 21 girls, mean age 10.6 +/- 3.6 years) were analyzed for nucleotide variations in the MC4R coding region, by the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) method followed by direct DNA sequencing.
Disruption of the signal transducer and activator of transcription 3 (STAT3) in the hypothalamic neurons expressing leptin receptor, results in severe obesity, hyperglycaemia, and hyperinsulinemia.
The purpose of the study was to investigate the association between the MC4RV103I polymorphism and the dietary intake of persons with severe obesity, which was derived by using the Willett food-frequency questionnaire.
Heterozygous MC4R mutations were associated with early-onset severe obesity, and homozygosity of the MC4R mutation Tyr157Ser resulted in morbid obesity.
Leptin is an adipocyte-secreted hormone, and deficiency of either leptin or its receptor has been shown to cause morbid obesity in animals and in humans.
Mutation screen of the MC4R in consecutively ascertained Austrian children and adolescents with severe obesity, to analyse the phenotype of mutation carriers and to functionally characterise novel mutations.
We and others have identified several single gene defects that disrupt the molecules in the leptin-melanocortin pathway causing severe obesity in humans.
To investigate the physiological role of leptin in the control of meal size and the response to satiety signals, and to identify brain areas mediating this effect, we studied Koletsky (fa(k)/fa(k)) rats, which develop severe obesity due to the genetic absence of leptin receptors.
We document here that 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.
To determine whether MC4R has a role in causing severe obesity in Pima Indians, we sequenced the coding region of this gene in 426 full-heritage, non-first-degree related, adult Pima Indians (300 severely obese and 126 nondiabetic nonobese control subjects).
The only situation in which obesity does not parallel leptin values is the rare case of morbid obesity due to leptin deficiency caused by missense mutation of the leptin gene.
Systematic screening of 431 obese children and adults for mutations in the coding sequence and the minimal core promoter of MC4R reveals that genetic variation in the transcriptionally essential region of the MC4R promoter is not a significant cause of severe obesity in humans.
In humans, mutations in leptin, leptin receptor, proopiomelanocortin (POMC), melanocortin-4 receptor (MC4R) and prohormone convertase 1 (PC1) have been described in patients with severe obesity.