Artículos de revistas
Testosterone activates glucose metabolism through AMPK and androgen signaling in cardiomyocyte hypertrophy
Fecha
2021Registro en:
Biol Res (2021) 54:3
10.1186/s40659-021-00328-4
Autor
Troncoso Magñin, Mayarling Francisca
Pavez Giani, Mario Gustavo
Wilson Rodríguez, Carlos Antonio
Lagos Cerón, Daniel Alejandro
Durán Gárate, Javier Andre
Ramos, Sebastián
Barrientos Briones, Genaro Christian
Silva, Patricio
Llanos Vidal, Paola Andrea
Basualto Alarcón, Carla Edith
Westenbrink, B. Daan
Lavandero González, Sergio Alejandro
Estrada Hormazábal, Manuel Iván
Institución
Resumen
Background Testosterone regulates nutrient and energy balance to maintain protein synthesis and metabolism in cardiomyocytes, but supraphysiological concentrations induce cardiac hypertrophy. Previously, we determined that testosterone increased glucose uptake-via AMP-activated protein kinase (AMPK)-after acute treatment in cardiomyocytes. However, whether elevated glucose uptake is involved in long-term changes of glucose metabolism or is required during cardiomyocyte growth remained unknown. In this study, we hypothesized that glucose uptake and glycolysis increase in testosterone-treated cardiomyocytes through AMPK and androgen receptor (AR). Methods Cultured cardiomyocytes were stimulated with 100 nM testosterone for 24 h, and hypertrophy was verified by increased cell size and mRNA levels of beta-myosin heavy chain (beta-mhc). Glucose uptake was assessed by 2-NBDG. Glycolysis and glycolytic capacity were determined by measuring extracellular acidification rate (ECAR). Results Testosterone induced cardiomyocyte hypertrophy that was accompanied by increased glucose uptake, glycolysis enhancement and upregulated mRNA expression of hexokinase 2. In addition, testosterone increased AMPK phosphorylation (Thr172), while inhibition of both AMPK and AR blocked glycolysis and cardiomyocyte hypertrophy induced by testosterone. Moreover, testosterone supplementation in adult male rats by 5 weeks induced cardiac hypertrophy and upregulated beta-mhc, Hk2 and Pfk2 mRNA levels. Conclusion These results indicate that testosterone stimulates glucose metabolism by activation of AMPK and AR signaling which are critical to induce cardiomyocyte hypertrophy.