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
Increased insulin and leptin sensitivity in mice lacking acyl CoA:diacylglycerol acyltransferase 1
Hubert C. Chen, … , Robert H. Eckel, Robert V. Farese Jr.
Hubert C. Chen, … , Robert H. Eckel, Robert V. Farese Jr.
Published April 15, 2002
Citation Information: J Clin Invest. 2002;109(8):1049-1055. https://doi.org/10.1172/JCI14672.
View: Text | PDF
Article Endocrinology

Increased insulin and leptin sensitivity in mice lacking acyl CoA:diacylglycerol acyltransferase 1

  • Text
  • PDF
Abstract

Acyl coenzyme A:diacylglycerol acyltransferase 1 (DGAT1) is one of two known DGAT enzymes that catalyze the final step in mammalian triglyceride synthesis. DGAT1-deficient mice are resistant to diet-induced obesity through a mechanism involving increased energy expenditure. Here we show that these mice have decreased levels of tissue triglycerides, as well as increased sensitivity to insulin and to leptin. Importantly, DGAT1 deficiency protects against insulin resistance and obesity in agouti yellow mice, a model of severe leptin resistance. In contrast, DGAT1 deficiency did not affect energy and glucose metabolism in leptin-deficient (ob/ob) mice, possibly due in part to a compensatory upregulation of DGAT2 expression in the absence of leptin. Our results suggest that inhibition of DGAT1 may be useful in treating insulin resistance and leptin resistance in human obesity.

Authors

Hubert C. Chen, Steven J. Smith, Zuleika Ladha, Dalan R. Jensen, Luis D. Ferreira, Leslie K. Pulawa, James G. McGuire, Robert E. Pitas, Robert H. Eckel, Robert V. Farese Jr.

×

Figure 4

Options: View larger image (or click on image) Download as PowerPoint
Expression of leptin-regulated genes in Dgat1–/– mice. The expression of...
Expression of leptin-regulated genes in Dgat1–/– mice. The expression of UCP1 was examined in BAT. The expression of other genes was examined in WAT. For PPARα and leptin, results were obtained with real-time PCR. For other genes, results were obtained with Northern blotting. n = 4–6 chow-fed male mice per genotype. *P < 0.05 versus Dgat1+/+ mice.

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

Sign up for email alerts