Open AccessDPP-4 inhibitor induces FGF21 expression via sirtuin 1 signaling and improves myocardial energy metabolism
Author(s) -
Nozomi Furukawa,
Norimichi Koitabashi,
Hiroki Matsui,
Hiroaki Sunaga,
Yogi Umbarawan,
Mas Rizky A. A. Syamsunarno,
Aiko Yamaguchi,
Masaru Obokata,
Hirofumi Hanaoka,
Tetsuji Yokoyama,
Masahiko Kurabayashi
Publication year - 2020
Publication title -
heart and vessels
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.624
H-Index - 46
eISSN - 1615-2573
pISSN - 0910-8327
DOI - 10.1007/s00380-020-01711-z
Subject(s) - fgf21 , endocrinology , medicine , sirtuin 1 , pressure overload , energy homeostasis , cardiac function curve , heart failure , dipeptidyl peptidase 4 , diabetes mellitus , type 2 diabetes , downregulation and upregulation , chemistry , fibroblast growth factor , cardiac hypertrophy , biochemistry , receptor , gene
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.