Mechanisms for LEPR-mediated regulation of leptin expression in brown and white adipocytes in rat pups

Abstract

To investigate the underlying mechanisms for leptin receptor (LEPR)-mediated regulation of leptin gene (Lep) expression in brown (BAT) and white (WAT) adipose tissue and resultant effects on plasma leptin concentrations (plasma-LEP), we examined effects of sympathetic nervous system (SNS) activity, caloric balance, and body fat content on leptin mRNA levels in BAT and WAT in 10-day-old rat pups segregating for Lepr(fa). In mother-reared pups, Lep mRNA levels were fa/fa > +/fa = +/+ in BAT and was fa/fa > +/fa > +/+ in WAT. The genotype effects on Lep expression in BAT and plasma-LEP were virtually eliminated when the differences in SNS activity between fa/fa and +/fa pups were equalized by artificial rearing of pups under thermoneutral conditions with or without oral norepinephrine (NE) administration. NE administration alone had little effect on the Lepr(fa)-dependent stratification of Lep expression in WAT. BAT-Lep mRNA was the main determinant of plasma-LEP. Metabolic rate, a surrogate indicator of SNS activity, explained 87% of the variation in BAT-Lep mRNA (R(2) = 0.93), whereas caloric balance (40%) and body fat mass (6%) accounted for most of the variation in WAT-Lep mRNA (R(2) = 0.53). We conclude that feedback regulation of Lep expression in BAT is primarily via central nervous system-mediated effects of leptin on SNS activity, whereas the control of leptin expression in WAT is more likely via mechanisms not directly dependent on SNS activity.