Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Site and mechanism of leptin action in a rodent form of congenital lipodystrophy
Esra Asilmaz, … , Nicholas D. Socci, Jeffrey M. Friedman
Esra Asilmaz, … , Nicholas D. Socci, Jeffrey M. Friedman
Published February 1, 2004
Citation Information: J Clin Invest. 2004;113(3):414-424. https://doi.org/10.1172/JCI19511.
View: Text | PDF
Article Metabolism Article has an altmetric score of 7

Site and mechanism of leptin action in a rodent form of congenital lipodystrophy

  • Text
  • PDF
Abstract

Lipodystrophy is characterized by the complete or partial absence of adipose tissue, insulin resistance, hepatic steatosis, and leptin deficiency. Here, we show that low-dose central leptin corrects the insulin resistance and fatty liver of lipodystrophic aP2-nSREBP-1c mice, while the same dose given peripherally does not. Central leptin also repressed stearoyl-CoA desaturase-1 (SCD-1) RNA and enzymatic activity, which were increased in livers of lipodystrophic mice. aP2-nSREBP-1c mice homozygous for an SCD-1 deletion had markedly reduced hepatic steatosis, increased saturated fatty acids, decreased acetyl-CoA carboxylase activity, and decreased malonyl-CoA levels in the liver. Despite the reduction in hepatic steatosis, these mice remained diabetic. A leptin dose-response curve showed that subcutaneous leptin improved hyperglycemia and hyperinsulinemia in aP2-nSREBP-1c mice at doses that did not substantially alter hepatic steatosis or hepatic SCD enzymatic activity. Leptin treatment at this dose improved insulin-stimulated insulin receptor and insulin receptor substrate 2 (IRS-2) phosphorylation, IRS-2–associated PI3K activity, and Akt activity in liver. Together, these data suggest that CNS-mediated repression of SCD-1 contributes to leptin’s antisteatotic actions. Intracerebroventricular leptin improves glucose homeostasis by improving insulin signal transduction in liver, but in this case the effect appears to be independent of SCD-1.

Authors

Esra Asilmaz, Paul Cohen, Makoto Miyazaki, Pawel Dobrzyn, Kohjiro Ueki, Gulnorakhon Fayzikhodjaeva, Alexander A. Soukas, C. Ronald Kahn, James M. Ntambi, Nicholas D. Socci, Jeffrey M. Friedman

×

Figure 5

Options: View larger image (or click on image) Download as PowerPoint
Correction of fatty liver but not diabetes in abJ/abJ;aP2-nSREBP-1c tran...
Correction of fatty liver but not diabetes in abJ/abJ;aP2-nSREBP-1c transgenic mice. (a) Gross liver appearance in abJ/abJ;aP2-nSREBP-1c transgenic mice, aP2-nSREBP-1c transgenic mice, and WT mice. (b) Representative liver sections from aP2-nSREBP-1c and abJ/abJ;aP2-nSREBP-1c mice. Original magnification, ×200; scale bars: 100 μm. (c) Liver triglyceride levels. (d) Fatty acid content in liver. (e) ACC activity in liver. (f) Malonyl-CoA levels in liver. (g and h) Plasma glucose and plasma insulin levels, respectively. Error bars indicate the SE; n = 7 for the aP2-nSREBP-1c group, n = 6 for the abJ/abJ;aP2-nSREBP-1c group, and n = 3 for the abJ/abJ group. *P < 0.05, abJ/abJ;aP2-nSREBP-1c vs. aP2-nSREBP-1c mice; †P < 0.05, aP2-nSREBP-1c vs. abJ/abJ or abJ/+; #P < 0.05 abJ/abJ;aP2-nSREBP-1c vs. abJ/abJ or abJ/+.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Posted by 1 X users
Referenced in 3 patents
21 readers on Mendeley
See more details