Testosterone activates glucose metabolism through AMPK and androgen signaling in cardiomyocyte hypertrophy

Mayarling Francisca Troncoso, Mario Pavez, Carlos Wilson, Daniel Lagos, Javier Duran, Sebastian Ramos, Genaro Barrientos, Patricio Silva, Paola Llanos, Carla Basualto-Alarcon, B. Daan Westenbrink, Sergio Lavandero, Manuel Estrada*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

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.

Original languageEnglish
Article number3
Number of pages16
JournalBiological research
Volume54
Issue number1
DOIs
Publication statusPublished - 5-Dec-2021

Keywords

  • Testosterone
  • AMP-activated protein kinase
  • Glucose transport
  • Glycolysis
  • Androgen receptor
  • Cardiac hypertrophy

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