Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
  • 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
    • Author's Takes
  • Reviews
    • View all reviews ...
    • Aging (Upcoming)
    • Next-Generation Sequencing in Medicine (Jun 2022)
    • New Therapeutic Targets in Cardiovascular Diseases (Mar 2022)
    • Immunometabolism (Jan 2022)
    • Circadian Rhythm (Oct 2021)
    • Gut-Brain Axis (Jul 2021)
    • Tumor Microenvironment (Mar 2021)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • In-Press Preview
  • Commentaries
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
Interplay between FGF21 and insulin action in the liver regulates metabolism
Brice Emanuelli, … , Alexei Kharitonenkov, C. Ronald Kahn
Brice Emanuelli, … , Alexei Kharitonenkov, C. Ronald Kahn
Published January 9, 2014
Citation Information: J Clin Invest. 2014;124(2):515-527. https://doi.org/10.1172/JCI67353.
View: Text | PDF | Corrigendum
Research Article

Interplay between FGF21 and insulin action in the liver regulates metabolism

  • Text
  • PDF
Abstract

The hormone FGF21 regulates carbohydrate and lipid homeostasis as well as body weight, and increasing FGF21 improves metabolic abnormalities associated with obesity and diabetes. FGF21 is thought to act on its target tissues, including liver and adipose tissue, to improve insulin sensitivity and reduce adiposity. Here, we used mice with selective hepatic inactivation of the IR (LIRKO) to determine whether insulin sensitization in liver mediates FGF21 metabolic actions. Remarkably, hyperglycemia was completely normalized following FGF21 treatment in LIRKO mice, even though FGF21 did not reduce gluconeogenesis in these animals. Improvements in blood sugar were due in part to increased glucose uptake in brown fat, browning of white fat, and overall increased energy expenditure. These effects were preserved even after removal of the main interscapular brown fat pad. In contrast to its retained effects on reducing glucose levels, the effects of FGF21 on reducing circulating cholesterol and hepatic triglycerides and regulating the expression of key genes involved in cholesterol and lipid metabolism in liver were disrupted in LIRKO mice. Thus, FGF21 corrects hyperglycemia in diabetic mice independently of insulin action in the liver by increasing energy metabolism via activation of brown fat and browning of white fat, but intact liver insulin action is required for FGF21 to control hepatic lipid metabolism.

Authors

Brice Emanuelli, Sara G. Vienberg, Graham Smyth, Christine Cheng, Kristin I. Stanford, Manimozhiyan Arumugam, Mervyn D. Michael, Andrew C. Adams, Alexei Kharitonenkov, C. Ronald Kahn

×

Figure 4

Energy homeostasis and BAT activation following chronic FGF21 treatment.

Options: View larger image (or click on image) Download as PowerPoint
Energy homeostasis and BAT activation following chronic FGF21 treatment....
Control and LIRKO mice on a CD or an HFD for 7 weeks were treated with saline or FGF21 (1 mg/kg/day) delivered s.c. by osmotic pump during the last 2 weeks of the diet. CLAMS analysis was determined for 3 days, starting on day 7 after insertion of the pumps. (A and B) O2 consumption in control (A) and LIRKO (B) animals on an HFD. Gray lines represent saline-treated mice; black lines represent FGF21-treated mice. (C) BAT weight. White bars represent saline-treated mice on a CD, black bars represent FGF21-treated mice on a CD, light gray bars represent saline-treated mice on an HFD, and dark gray bars represent FGF21-treated mice on an HFD. (D) H&E staining of s.c. adipose tissue sections from LIRKO mice. Original magnification, ×40. (E) Ucp1 expression in s.c. adipose tissue determined by qPCR. Data represent the means ± SEM. P values were determined by 3-way ANOVA analysis.

Copyright © 2022 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts