Lif and cntf, which share the gp130 transduction system, stimulate
hepatic lipid metabolism in rats.
Nonogaki, Katsunori, Xian-Mang Pan, Arthur H. Moser, Judy Shigenaga,
Ilona Staprans, Nobuo Sakamoto, Carl Grunfeld, and Kenneth R.
Feingold.
Department of Medicine, University of California, San Francisco,
Metabolism Section and Lipid Research Laboratory, Department of
Veterans Affairs Medical Center, San Francisco, California and Third
Department of Internal Medicine, Nagoya University School of
Medicine, Tsuruma-cho, Showa-ku, Nagoya, 65. Japan
APStracts 3:0096E, 1996.
We determined the effects of leukemia inhibitory factor (LIF) and
ciliary neurotrophic factor (CNTF) on lipid metabolism in intact
rats. Administration of LIF and CNTF increased serum triglycerides in
a dose dependent manner with peak values at 2 hours. The effects of
LIF and CNTF on serum cholesterol was very small and serum glucose
was unaffected. Both LIF and CNTF stimulated hepatic triglyceride
secretion, hepatic de novo fatty acid synthesis and lipolysis.
Pretreatment with phenylisopropyladenosine (PIA), which inhibits
lipolysis, partially inhibited LIF and CNTF-induced
hypertriglyceridemia. IL-4, which inhibits cytokine-induced hepatic
fatty acid synthesis, also partially inhibited LIF and CNTF-induced
hypertriglyceridemia. These results indicate that both lipolysis and
de novo fatty acid synthesis play a role in providing fatty acids for
the increase in hepatic triglyceride secretion. Neither indomethacin
nor adrenergic receptor antagonists affected the
hypertriglyceridemia. The combination of LIF plus CNTF showed no
additive effects consistent with the action of both cytokines through
the gp130 transduction system. Thus, LIF and CNTF have similar
effects on lipid metabolism; they join a growing list of cytokines
that stimulate hepatic triglyceride secretion and may mediate the
changes in lipid metabolism that accompany the acute phase response.
Received 31 October 1995; accepted in final form 23 April 1996.
APS Manuscript Number E518-5.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 8 May 96