These include the hormone leptin, the short and long forms of the leptin receptor, uncoupling proteins, agouti protein, melanocortin receptor isoforms, melanin-concentrating hormone, and the proteins responsible for tub and fat, two monogenic mouse models of obesity.
In conclusion, it is unlikely that mutations in the coding region of the long isoform of the leptin receptor are a common cause of juvenile onset obesity.
Effects of diet-induced obesity and voluntary exercise in a tauopathy mouse model: implications of persistent hyperleptinemia and enhanced astrocytic leptin receptor expression.
Protein tyrosine phosphatase 1B (PTP1B) has been considered as a promising therapeutic target for type 2 diabetes mellitus (T2DM) and obesity due to its key regulating effects in insulin signaling and leptin receptor pathways.
Since CCX140-B has a low affinity for mouse CCR2, transgenic human CCR2 knockin mice were generated and rendered diabetic with either a high-fat diet (diet-induced obesity) or by deletion of the leptin receptor gene (db/db).
Leptin plays an important role in the regulation of body fat homeostasis, and potential associations of leptin receptor gene (LEPR) polymorphisms with obesity have been suggested.
LEPRrs1137101 GG genotype was related to reduced risk of obesity (odds ratio [OR] 0.26, 95% confidence interval [CI] 0.08-0.79; p = 0.018) and MetS (OR 0.36, 95% CI 0.15-0.88; p = 0.024), but it was not significant after Bonferroni correction for multiple tests as compared to the AA genotype (p > 0.01).
Obesity did not correlate with protein serum levels.We observed that obesity is more frequent in children with LEPR 223 AG+GG and LEPR 1019 GA+AA genotypes.
Although the effects of leptin have been more thoroughly documented in nonprimate species than in primates, a few human families with genetic mutations of the gene for leptin or the leptin receptor show obesity and impaired fertility.
Recently published results revealed linkage of obesity traits to a chromosomal region near the leptin receptor gene (Lepr) locus in high body weight selected big and fat DU6i mice.
Our results suggest that dietary fat intake modifies the effect of APOA5 and LEPR polymorphisms on serum triglycerides, cholesterol levels and obesity in young subjects.
Therapeutic approaches to the treatment of obesity based on OB protein ranging from OB protein by injection to OB-R receptor agonists and to upregulation of OB signalling pathways are under intense investigation.
The aim of this study was to evaluate a genetically homogeneous population for associations between body composition variables and three common leptin receptor gene polymorphisms (K109R, Q223R, and K656N) that have potential functional significance as well as to assess the contributions of these polymorphisms to the variability of obesity.
We present a 3-year-old male patient with severe early-onset obesity whose genetic analysis revealed a homozygous, novel, and pathogenic variant (c.1603+2T>C) in LEPR.
Protein tyrosine phosphatase 1B (PTP1B) is a major negative regulator of both the insulin and leptin receptor phosphorylation which impacts insulin sensitivity and hence is a major therapeutic target for the treatment of type 2 diabetes and obesity.