The leptin receptor mediates apparent autocrine regulation of leptin gene expression.

The possibility that the leptin receptor (LEPR) mediates autocrine regulation of leptin expression in adipose tissue was examined in 10-day-old Zucker rat pups with different copy numbers of the leptin receptor mutation (Lepr(fa)). Plasma leptin concentrations and adipose tissue mRNA levels for leptin were related to copy number of the mutation (fa/fa > fa/+ > +/+). These relationships were independent of plasma insulin concentration. Reduced copy number for the functional leptin receptor apparently results in a diminished negative feedback signal to the leptin gene in adipose tissue. Thus, leptin appears to close a short regulatory loop controlling its own synthesis in adipose tissue.