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Open Access 01-01-2021 | Heart Failure | Original Article

DPP-4 inhibitor induces FGF21 expression via sirtuin 1 signaling and improves myocardial energy metabolism

Authors: Nozomi Furukawa, Norimichi Koitabashi, Hiroki Matsui, Hiroaki Sunaga, Yogi Umbarawan, Mas Rizky A. A. Syamsunarno, Aiko Yamaguchi, Masaru Obokata, Hirofumi Hanaoka, Tomoyuki Yokoyama, Masahiko Kurabayashi

Published in: Heart and Vessels | Issue 1/2021

Abstract

Dipeptidyl peptidase-4 (DPP-4) inhibitors are widely used incretin-based therapy for the treatment of type 2 diabetes. We investigated the cardioprotective effect of a DPP-4 inhibitor, vildagliptin (vilda), on myocardial metabolism and cardiac performance under pressure overload. Mice were treated with either vehicle or vilda, followed by transverse aortic constriction (TAC). After 3 weeks of TAC, cardiac hypertrophy and impairment of systolic function were attenuated in vilda-treated mice. Pressure–volume analysis showed that vilda treatment significantly improved left-ventricular contractile efficiency in TAC heart. Myocardial energy substrate analysis showed that vilda treatment significantly increased glucose uptake as well as fatty acid uptake. Fibroblast growth factor 21 (FGF21), a peptide involved in the regulation of energy metabolism, increased in TAC heart and was further increased by vilda treatment. FGF21 was strongly expressed in cardiac fibroblasts than in cardiomyocytes in mouse heart after TAC with vilda treatment. Vilda treatment markedly induced FGF21 expression in human cardiac fibroblasts through a sirtuin (Sirt) 1-mediated pathway, suggesting that fibroblast-mediated FGF21 expression may regulate energy metabolism and exert vilda-mediated beneficial effects in stressed heart. Vilda induced a metabolic regulator, FGF21 expression in cardiac fibroblasts via Sirt1, and increased contractile efficiency in murine pressure-overloaded heart.

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Title: DPP-4 inhibitor induces FGF21 expression via sirtuin 1 signaling and improves myocardial energy metabolism
Authors: Nozomi Furukawa
Norimichi Koitabashi
Hiroki Matsui
Hiroaki Sunaga
Yogi Umbarawan
Mas Rizky A. A. Syamsunarno
Aiko Yamaguchi
Masaru Obokata
Hirofumi Hanaoka
Tomoyuki Yokoyama
Masahiko Kurabayashi
Publication date: 01-01-2021
Publisher: Springer Japan
Keywords: Heart Failure
Vildagliptin
Published in: Heart and Vessels / Issue 1/2021
Print ISSN: 0910-8327
Electronic ISSN: 1615-2573
DOI: https://doi.org/10.1007/s00380-020-01711-z

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