Mouse models of obesity (ob/ob) and diabetes (db/db) in which the leptin (Lep) and leptin receptor (Lepr) genes have been mutated, respectively, have contributed to a better understanding of human obesity and type 2 diabetes and to the prevention, diagnosis, and treatment of these metabolic diseases.
Through phenotyping of the resulting three lines of rats bearing distinct mutations in the Lepr locus, we found that the strains with a frame-shifted or premature stop codon mutation led to obesity and metabolic disorders.
We considered blood cells as a new potential source of transcriptional biomarkers for these metabolic disorders and examined whether blood cell mRNA levels of some selected genes (LEPR, INSR, CPT1A, SLC27A2, UCP2, FASN, and PPARα) were altered in overweight children and whether their expression levels could be defined as markers of the insulin-resistant or dyslipidemic state associated with overweight.
This study indicates that leptin may act as a growth-promoting signal during fetal development, and suggests a possible role for the LEPR in explaining the inverse relationship between birth weight and the development of metabolic diseases in adulthood.
This study indicates that leptin may act as a growth-promoting signal during fetal development, and suggests a possible role for the LEPR in explaining the inverse relationship between birth weight and the development of metabolic diseases in adulthood.
The understanding of the putative direct leptin signaling pathway in skeletal muscle could be an important step towards the utilization of leptin or a leptin receptor agonist as therapeutic tools to treat obesity and its related metabolic disorders.