Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising/recruitment
  • Contact
  • Current Issue
  • Past Issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Recently published
    • Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Recently published
  • In-Press Preview
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising/recruitment
  • Contact
Vasopressin mediates fructose-induced metabolic syndrome by activating the V1b receptor
Ana Andres-Hernando, … , Richard J. Johnson, Miguel A. Lanaspa
Ana Andres-Hernando, … , Richard J. Johnson, Miguel A. Lanaspa
Published December 15, 2020
Citation Information: JCI Insight. 2021;6(1):e140848. https://doi.org/10.1172/jci.insight.140848.
View: Text | PDF
Research Article Endocrinology Metabolism

Vasopressin mediates fructose-induced metabolic syndrome by activating the V1b receptor

  • Text
  • PDF
Abstract

Subjects with obesity frequently have elevated serum vasopressin levels, noted by measuring the stable analog, copeptin. Vasopressin acts primarily to reabsorb water via urinary concentration. However, fat is also a source of metabolic water, raising the possibility that vasopressin might have a role in fat accumulation. Fructose has also been reported to stimulate vasopressin. Here, we tested the hypothesis that fructose-induced metabolic syndrome is mediated by vasopressin. Orally administered fructose, glucose, or high-fructose corn syrup increased vasopressin (copeptin) concentrations and was mediated by fructokinase, an enzyme specific for fructose metabolism. Suppressing vasopressin with hydration both prevented and ameliorated fructose-induced metabolic syndrome. The vasopressin effects were mediated by the vasopressin 1b receptor (V1bR), as V1bR-KO mice were completely protected, whereas V1a-KO mice paradoxically showed worse metabolic syndrome. The mechanism is likely mediated in part by de novo expression of V1bR in the liver that amplifies fructokinase expression in response to fructose. Thus, our studies document a role for vasopressin in water conservation via the accumulation of fat as a source of metabolic water. Clinically, they also suggest that increased water intake may be a beneficial way to both prevent or treat metabolic syndrome.

Authors

Ana Andres-Hernando, Thomas J. Jensen, Masanari Kuwabara, David J. Orlicky, Christina Cicerchi, Nanxing Li, Carlos A. Roncal-Jimenez, Gabriela E. Garcia, Takuji Ishimoto, Paul S. Maclean, Petter Bjornstad, Laura Gabriela Sanchez-Lozada, Mehmet Kanbay, Takahiko Nakagawa, Richard J. Johnson, Miguel A. Lanaspa

×

Figure 4

Lowering vasopressin as a therapeutic intervention in mice with sugar-induced metabolic syndrome.

Options: View larger image (or click on image) Download as PowerPoint
Lowering vasopressin as a therapeutic intervention in mice with sugar-in...
(A) Weekly body weight gain in mice receiving water (red-dashed line) or HFCS (red solid line) for 30 weeks. At week 15 a subgroup of HFCS started the intervention with hydrogels (HFCS-HWI, blue solid line). (B) 30-week serum copeptin levels in water, HFCS, and HFCS-HWI groups. (C) 30-week urinary volume excretion (mL urine/24 hour) in water, HFCS, and HFCS-HWI groups. (D) Representative H&E images from livers of mice (n > 10 images per animal) of the same groups as in A at 30 weeks. Size bars: 50 μM. (E) 30-week serum ALT levels in water, HFCS, and HFCS-HWI groups. (F) 30-week serum Insulin levels in water, HFCS, and HFCS-HWI groups. (G) 30-week serum leptin levels in water, HFCS, and HFCS-HWI groups. (H) 30-week fat mass to total body weight percentage in water, HFCS, and HFCS-HWI groups. (I) Representative H&E images from epididymal adipose tissue of mice (n > 10 images per animal) on HFCS or HFCS-HWI groups. Size bars: 50 μM. The data in A–C and E–H are presented as the mean and analyzed by 1-way ANOVA with Tukey’s post hoc. The data for A were collected and analyzed weekly, whereas the data for B and C and E–H were collected and analyzed every 5 weeks. *P < 0.05, **P < 0.01. n = 6 mice per group. See also Supplemental Figure 1 and Supplemental Table 4. HFCS, high-fructose corn syrup; HWI, high water intake; PT, portal triad; CV, central vein; ALT, alanine aminotransferase.
Follow JCI Insight:
Copyright © 2021 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts