Mechanisms for LEPR-mediated regulation of leptin expression in brown and white adipocytes in rat pups.
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.
Zhang
Y
Y
Division of Molecular Genetics, Department of Pediatrics, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA. yz84@columbia.edu
Hufnagel
C
C
Eiden
S
S
Guo
K Y
KY
Diaz
P A
PA
Leibel
R
R
Schmidt
I
I
D017667:Adipocytes / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002149:Energy Intake / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology; D005260:Female; D018628:Gene Dosage; D005786:Gene Expression Regulation; D005838:Genotype; D020738:Leptin / Q000097:blood / Q000235:genetics*; D008297:Male; D015999:Multivariate Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D012044:Regression Analysis; D013564:Sympathetic Nervous System / Q000502:physiology
D002352:Carrier Proteins; D020738:Leptin; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin