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Norepinephrine induces hepatic fibrogenesis in leptin deficient ob/ob mice.

Publication ,  Journal Article
Oben, JA; Roskams, T; Yang, S; Lin, H; Sinelli, N; Li, Z; Torbenson, M; Thomas, SA; Diehl, AM
Published in: Biochem Biophys Res Commun
August 22, 2003

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.

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Published In

Biochem Biophys Res Commun

DOI

ISSN

0006-291X

Publication Date

August 22, 2003

Volume

308

Issue

2

Start / End Page

284 / 292

Location

United States

Related Subject Headings

  • Transforming Growth Factor beta1
  • Transforming Growth Factor beta
  • Sympathetic Nervous System
  • Rats, Sprague-Dawley
  • Rats
  • Norepinephrine
  • Mice, Obese
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
 

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Oben, J. A., Roskams, T., Yang, S., Lin, H., Sinelli, N., Li, Z., … Diehl, A. M. (2003). Norepinephrine induces hepatic fibrogenesis in leptin deficient ob/ob mice. Biochem Biophys Res Commun, 308(2), 284–292. https://doi.org/10.1016/s0006-291x(03)01360-3
Oben, Jude A., Tania Roskams, Shiqi Yang, Huizhi Lin, Nicoletta Sinelli, Zhiping Li, Michael Torbenson, Steven A. Thomas, and Anna Mae Diehl. “Norepinephrine induces hepatic fibrogenesis in leptin deficient ob/ob mice.Biochem Biophys Res Commun 308, no. 2 (August 22, 2003): 284–92. https://doi.org/10.1016/s0006-291x(03)01360-3.
Oben JA, Roskams T, Yang S, Lin H, Sinelli N, Li Z, et al. Norepinephrine induces hepatic fibrogenesis in leptin deficient ob/ob mice. Biochem Biophys Res Commun. 2003 Aug 22;308(2):284–92.
Oben, Jude A., et al. “Norepinephrine induces hepatic fibrogenesis in leptin deficient ob/ob mice.Biochem Biophys Res Commun, vol. 308, no. 2, Aug. 2003, pp. 284–92. Pubmed, doi:10.1016/s0006-291x(03)01360-3.
Oben JA, Roskams T, Yang S, Lin H, Sinelli N, Li Z, Torbenson M, Thomas SA, Diehl AM. Norepinephrine induces hepatic fibrogenesis in leptin deficient ob/ob mice. Biochem Biophys Res Commun. 2003 Aug 22;308(2):284–292.
Journal cover image

Published In

Biochem Biophys Res Commun

DOI

ISSN

0006-291X

Publication Date

August 22, 2003

Volume

308

Issue

2

Start / End Page

284 / 292

Location

United States

Related Subject Headings

  • Transforming Growth Factor beta1
  • Transforming Growth Factor beta
  • Sympathetic Nervous System
  • Rats, Sprague-Dawley
  • Rats
  • Norepinephrine
  • Mice, Obese
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice