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Title: Norepinephrine induces hepatic fibrogenesis in leptin deficient ob/ob mice
Authors: Oben, Jude A ×
Roskams, Tania
Yang, Shiqi
Lin, Huizhi
Sinelli, Nicoletta
Li, Zhiping
Torbenson, Michael
Thomas, Steven A
Diehl, Anna Mae #
Issue Date: Aug-2003
Series Title: Biochemical and Biophysical Research Communications vol:308 issue:2 pages:284-92
Abstract: Leptin's actions on certain cells require a leptin-inducible neurotransmitter, norepinephrine (NE). NE modulates hepatic fibrosis. Therefore, decreased NE may explain why leptin deficiency inhibits hepatic fibrosis. We manipulated adrenergic activity in leptin-deficient ob/ob mice, leptin-sufficient, dopamine beta-hydroxylase deficient (Dbh(-/-)) mice, and HSC cultures to determine if leptin requires NE to activate HSC and induce hepatic fibrosis. ob/ob mice have chronic liver injury, but reduced numbers of HSC. Supplemental leptin increases HSC, suggesting that leptin-dependent, injury-related factors permit expansion of HSC populations. NE also increases HSC numbers and activation, normalizing fibrogenesis. When fed hepatotoxic diets, NE-deficient Dbh(-/-) mice fail to accumulate activated HSC and have impaired fibrogenesis unless treated with adrenergic agonists. NE acts directly on HSC to modulate leptin's actions because leptin increases HSC proliferation and prazosin, an alpha-adrenoceptor antagonist, inhibits this. Thus, leptin permits injury-related increases in adrenergic activity and requires NE to activate HSC and induce hepatic fibrogenesis.
URI: 
ISSN: 0006-291X
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Translational Cell & Tissue Research
Hematology Section (-)
× corresponding author
# (joint) last author

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