The massive obesity caused in rodents by the disruption of the leptin-receptor signal through genetic defects at the level of either leptin (OB) or leptin receptor (OB-R) has raised the question of the relevance of these genes to morbid obesity in humans.
In order to examine the involvement of leptin in the ossification of spinal ligaments (OSL), the present study examined (i) serum levels of leptin and insulin in OSL patients and controls, (ii) serum leptin levels in children of OSL females with severe obesity, (iii) the expression of leptin receptor mRNA in human spinal ligaments, and (iv) effects of leptin on cultured human ligament cells.
The massive obesity caused in rodents by the disruption of the leptin-receptor signal through genetic defects at the level of either leptin (OB) or leptin receptor (OB-R) has raised the question of the relevance of these genes to morbid obesity in humans.
The discovery of the adipocyte hormone leptin and the demonstration that severe obesity in ob/ob and db/db mice results from mutation of genes encoding leptin and its receptor, respectively, ushered in a new era of obesity research.
Loss of function (LoF) mutations in the MC4R pathway, including mutations in the pro-opiomelanocortin (POMC), prohormone convertase 1 (PCSK1), leptin receptor (LEPR), or MC4R genes, have been shown to cause early-onset severe obesity.
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.
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.
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.
We have assessed the incidence of LEP and MC4R mutations and associated hormonal profiles, in a cohort of randomly selected Pakistani children with early onset of severe obesity.
Among 73 children with severe obesity (BMI SDS > 3.0), we identified 22 probands and 5 relatives, carrying 10 different loss-of-function homozygous mutations in LEP, leptin receptor (LEPR), and MC4R genes, including 4 novel variants.
In this issue, we have gathered together a group of essays by some of the world leaders in leptin research, including an overview by Dr Jeffrey Friedman who, in his seminal article in December 1994, described the adipocyte-derived hormone, the lack of which was responsible for the severe obesity in ob/ob mice and suggested that it should be named leptin.
Heterozygous MC4R mutations were associated with early-onset severe obesity, and homozygosity of the MC4R mutation Tyr157Ser resulted in morbid obesity.
Evaluation of 29 SNPs (P < 1 × 10(-5)) in an additional 971 severely obese children and 1,990 controls identified 4 new loci associated with severe obesity (LEPR, PRKCH, PACS1 and RMST).
In rodents, homozygous mutations in genes encoding leptin or the leptin receptor cause early-onset morbid obesity, hyperphagia and reduced energy expenditure.