Effect of lactate on intermediary metabolites expression and mitochondrial biogenesis in perfused hearts (864.5)

Abstract

The aim of this study was to investigate whether lactate would modulates the expression of genes and proteins related to intermediary metabolism and mitochondrial biogenesis, and its impact on cardiac hemodynamic function. The hearts excised from male healthy rats were perfused with or without lactate (20mM) in Krebs‐Henseleit solution along 120 min in a Langendorff apparatus. Hemodynamic values including of perfusion pressure (PP) were acquired during the experiment. PPARδ, PGC1‐α, COXIV, MCT1, MCT4 and LDH mRNA levels were quantified by real time RT‐PCR. Mitochondrial DNA replication was evaluated, comparing COXII mRNA levels, a specific mitochondrial gene.Protein expression was assessed by Western Blot. The activity of hexokinase, lactate dehydrogenase, pyruvate dehydrogenase, citrate synthase, superoxide dismutase (SOD) and catalase were analyzed by colorimetry and spectrophotometry. Significant differences were accepted when P□0.05. The lactate concentration in the heart tissue was elevated in lactate group at 120 min (1.5 ± 1.2 vs. 4.8 ± 0.7 mM). This response was paralleled by a significant increase in mRNA levels of PPARδ (2.3x), PGC1‐α (4.5x), MCT1 (8.0x), MCT4 (4.0x) and LDH (13.7x) when compared to control group. No differences were observed in mitochondrial DNA replication, COX IV mRNA levels and activity of all enzymes, excepted for SOD that was significantly increased in lactate (26.6 ± 12.1 vs 92.3 ± 25.7 µmol/mg/min). PP value reduced after lactate perfusion (74.2 ± 10.3 vs 27.8 ± 6.8 mmHg). Our results provide evidence that lactate up‐regulates the expression of genes involved in cardiac bioenergetics and mitochondrial biogenesis, which might favor cardiac oxygenation.Grant Funding Source: FAPESP