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

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • 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 6

Hepatic V1bR potentiates the lipogenic effects of fructose.

Options: View larger image (or click on image) Download as PowerPoint
Hepatic V1bR potentiates the lipogenic effects of fructose.
(A) Transcri...
(A) Transcriptional levels of the avpr1b in hypothalamus, pancreas, jejunum, kidney, liver, and spleen of WT mice on water Ctrl (clear purple bars) or receiving a 10% Frct solution for 30 weeks (solid purple bars). (B) Transcriptional levels of the avpr1a (red line) and the avpr1b (purple line) in liver of WT mice receiving a 10% Frct solution for 30 weeks. (C and D) Representative Western blot and densitometry (n = 2 total blots) for the V1bR, fructokinase (KHK), and actin in human HepG2 cells Ctrl or exposed to AVP (250 nM), Frct (10 mM), or a combination of Frct plus AVP for 5 days. (E) KHK activity in HepG2 lysates from Ctrl, AVP, Frct, and Frct plus AVP cells. (F) Representative Western blot and densitometry (n = 2 total blots) for V1bR and actin in HepG2 transduced with noncodifying shRNA (scr) or shRNA against avpr1b (shAvpr1b) at baseline or a Frct (10 mM) exposure. (G) Representative Western blot and densitometry (n = 2 total blots) for KHK and actin in Ctrl, AVP, Frct, and Frct plus AVP HepG2 cells stably silenced for V1bR expression. (H and I) Representative Western blot (n = 2 total blots) and densitometry for KHK, actin, and lipogenic enzymes FAS and ACC in the liver of WT and V1bR-KO mice on water Ctrl or receiving a 10% Frct solution for 30 weeks. The data in A and C–E are presented as the mean ± SD and analyzed by 1-way ANOVA with Tukey’s post hoc analysis. *P < 0.05, **P < 0.01. For A and B and E, n = 6 mice per group. For C–E, n = 2 independent cultured plates. V1bR, vasopressin 1b receptor; avpr1b, vasopressin 1b receptor gene; avpr1a, vasopressin 1a receptor gene; KHK, ketohexokinase; Ctrl, control; AVP, vasopressin; Frct, fructose; scr, scramble; FAS, fatty acid synthase; ACC, acetyl-CoA carboxylase.

Copyright © 2022 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts