Lactate modulates cardiac gene expression in mice during acute physical exercise

Author(s)

T.F. Cunha ; J.S. Vieira ^[2] ; J.B. Santos ^[3] ; M.A. Coelho ^[4] ; P.C. Brum ^[5] ; D. Gabriel-Costa

• Document type: Journal article
• Source: Brazilian Journal of Medical and Biological Research; v. 55, 2022-04-27.

Abstract

The aim of the present study was to verify the role of lactate as a signaling molecule in cardiac tissue under physiological conditions. C57BL6/J male mice were submitted to acute running bouts on a treadmill at different exercise intensities (30, 60, and 90% of maximal speed - Smax) under the effect of two doses (0.5 and 5 mM) of α-cyano-4-hydroxycynnamate (CINN), a blocker of lactate transporters. Cardiac lactate levels, activity of the enzymes of glycolytic [hexokinase (HK) and lactate dehydrogenase (LDH)] and oxidative metabolism [citrate synthase (CS)], and expression of genes also related to metabolism [LDH, nuclear factor erythroid 2-related factor 2 (NRF-2), cytochrome oxidase IV (COX-IV), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)] were evaluated. Elevated cardiac lactate levels were observed after high intensity running at 90% of Smax, which were parallel to increased activity of the HK and CS enzymes and mRNA levels of PGC-1α and COX-IV. No changes were observed in cardiac lactate levels in mice running at lower exercise intensities. Interestingly, prior intraperitoneal administration (15 min) of CINN (0.5 mM) significantly reduced cardiac lactate concentration, activities of HK and CS, and mRNA levels of PGC-1α and COX-IV in mice that ran at 90% of Smax. In addition, cardiac lactate levels were significantly correlated to both PGC-1α and COX-IV cardiac gene expression. The present study provides evidence that cardiac lactate levels are associated to gene transcription during an acute bout of high intensity running exercise. (AU)

• FAPESP's process: 14/25957-9 - Influence of aerobic fitness in redox homeostasis: identification and biological implications of cysteine residues oxidation in cardiac and skeletal muscle proteins
• Grantee: Rodrigo Wagner Alves de Souza
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 15/22814-5 - Cancer and heart: new paradigms of diagnosis and treatment
• Grantee: Carlos Eduardo Negrão
• Support Opportunities: Research Projects - Thematic Grants