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Circulating Levels of Soluble Dipeptidyl Peptidase-4 Are Dissociated from Inflammation and Induced by Enzymatic DPP4 Inhibition.

Publication ,  Journal Article
Varin, EM; Mulvihill, EE; Beaudry, JL; Pujadas, G; Fuchs, S; Tanti, J-F; Fazio, S; Kaur, K; Cao, X; Baggio, LL; Matthews, D; Campbell, JE; Drucker, DJ
Published in: Cell Metab
February 5, 2019

Dipeptidyl peptidase-4 (DPP-4) controls glucose homeostasis through enzymatic termination of incretin action. We report that plasma DPP-4 activity correlates with body weight and fat mass, but not glucose control, in mice. Genetic disruption of adipocyte Dpp4 expression reduced plasma DPP-4 activity in older mice but did not perturb incretin levels or glucose homeostasis. Knockdown of hepatocyte Dpp4 completely abrogated the obesity-associated increase in plasma DPP-4 activity, reduced liver cytokine expression, and partially attenuated inflammation in adipose tissue without changes in incretin levels or glucose homeostasis. In contrast, circulating levels of soluble DPP4 (sDPP4) were dissociated from inflammation in mice with endothelial-selective or global genetic inactivation of Dpp4. Remarkably, inhibition of DPP-4 enzymatic activity upregulated circulating levels of sDPP4 originating from endothelial or hematopoietic cells without inducing systemic or localized inflammation. Collectively, these findings reveal unexpected complexity in regulation of soluble versus enzymatic DPP-4 and control of inflammation and glucose homeostasis.

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Published In

Cell Metab

DOI

EISSN

1932-7420

Publication Date

February 5, 2019

Volume

29

Issue

2

Start / End Page

320 / 334.e5

Location

United States

Related Subject Headings

  • Obesity
  • Mice, Inbred C57BL
  • Mice
  • Inflammation
  • Incretins
  • Hepatocytes
  • Glucose
  • Endocrinology & Metabolism
  • Dipeptidyl Peptidase 4
  • Cytokines
 

Citation

APA
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Varin, E. M., Mulvihill, E. E., Beaudry, J. L., Pujadas, G., Fuchs, S., Tanti, J.-F., … Drucker, D. J. (2019). Circulating Levels of Soluble Dipeptidyl Peptidase-4 Are Dissociated from Inflammation and Induced by Enzymatic DPP4 Inhibition. Cell Metab, 29(2), 320-334.e5. https://doi.org/10.1016/j.cmet.2018.10.001
Varin, Elodie M., Erin E. Mulvihill, Jacqueline L. Beaudry, Gemma Pujadas, Shai Fuchs, Jean-François Tanti, Sofia Fazio, et al. “Circulating Levels of Soluble Dipeptidyl Peptidase-4 Are Dissociated from Inflammation and Induced by Enzymatic DPP4 Inhibition.Cell Metab 29, no. 2 (February 5, 2019): 320-334.e5. https://doi.org/10.1016/j.cmet.2018.10.001.
Varin EM, Mulvihill EE, Beaudry JL, Pujadas G, Fuchs S, Tanti J-F, et al. Circulating Levels of Soluble Dipeptidyl Peptidase-4 Are Dissociated from Inflammation and Induced by Enzymatic DPP4 Inhibition. Cell Metab. 2019 Feb 5;29(2):320-334.e5.
Varin, Elodie M., et al. “Circulating Levels of Soluble Dipeptidyl Peptidase-4 Are Dissociated from Inflammation and Induced by Enzymatic DPP4 Inhibition.Cell Metab, vol. 29, no. 2, Feb. 2019, pp. 320-334.e5. Pubmed, doi:10.1016/j.cmet.2018.10.001.
Varin EM, Mulvihill EE, Beaudry JL, Pujadas G, Fuchs S, Tanti J-F, Fazio S, Kaur K, Cao X, Baggio LL, Matthews D, Campbell JE, Drucker DJ. Circulating Levels of Soluble Dipeptidyl Peptidase-4 Are Dissociated from Inflammation and Induced by Enzymatic DPP4 Inhibition. Cell Metab. 2019 Feb 5;29(2):320-334.e5.
Journal cover image

Published In

Cell Metab

DOI

EISSN

1932-7420

Publication Date

February 5, 2019

Volume

29

Issue

2

Start / End Page

320 / 334.e5

Location

United States

Related Subject Headings

  • Obesity
  • Mice, Inbred C57BL
  • Mice
  • Inflammation
  • Incretins
  • Hepatocytes
  • Glucose
  • Endocrinology & Metabolism
  • Dipeptidyl Peptidase 4
  • Cytokines