Here's another one (it supports LGND's leptin signaling program):
J Clin Invest 1997 Dec 1;100(11):2858-2864
Direct effects of leptin on brown and white adipose tissue.
Siegrist-Kaiser CA, Pauli V, Juge-Aubry CE, Boss O, Pernin A, Chin WW, Cusin I,
Rohner-Jeanrenaud F, Burger AG, Zapf J, Meier CA
Unite de Thyroide, Division d'Endocrinologie et Diabetologie, Hopital Universitaire de Geneve,
Geneva, Switzerland.
Leptin is thought to exert its actions on energy homeostasis through the long form of the leptin
receptor (OB-Rb), which is present in the hypothalamus and in certain peripheral organs, including
adipose tissue. In this study, we examined whether leptin has direct effects on the function of brown
and white adipose tissue (BAT and WAT, respectively) at the metabolic and molecular levels. The
chronic peripheral intravenous administration of leptin in vivo for 4 d resulted in a 1.6-fold increase
in the in vivo glucose utilization index of BAT, whereas no significant change was found after
intracerebroventricular administration compared with pair-fed control rats, compatible with a direct
effect of leptin on BAT. The effect of leptin on WAT fat pads from lean Zucker Fa/ fa rats was
assessed ex vivo, where a 9- and 16-fold increase in the rate of lipolysis was observed after 2 h of
exposure to 0.1 and 10 nM leptin, respectively. In contrast, no increase in lipolysis was observed in
the fat pads from obese fa/fa rats, which harbor an inactivating mutation in the OB-Rb. At the level
of gene expression, leptin treatment for 24 h increased malic enzyme and lipoprotein lipase RNA
1.8+/-0.17 and 1.9+/-0.14-fold, respectively, while aP2 mRNA levels were unaltered in primary
cultures of brown adipocytes from lean Fa/fa rats. Importantly, however, no significant effect of
leptin was observed on these genes in brown adipocytes from obese fa/fa animals. The presence of
OB-Rb receptors in adipose tissue was substantiated by the detection of its transcripts by RT-PCR,
and leptin treatment in vivo and in vitro activated the specific STATs implicated in the signaling
pathway of the OB-Rb. Taken together, our data strongly suggest that leptin has direct effects on
BAT and WAT, resulting in the activation of the Jak/STAT pathway and the increased expression of
certain target genes, which may partially account for the observed increase in glucose utilization and
lipolysis in leptin-treated adipose tissue.
PMID: 9389752, UI: 98052590 |
