Impact of metabolic stress induced by diets, aging and fasting on tissue oxygen consumption


  • O. Mackert
  • E.K. Wirth
  • R. Sun
  • J. Winkler
  • A. Liu
  • K. Renko
  • S. Kunz
  • J. Spranger
  • S. Brachs


  • Molecular Metabolism


  • Mol Metab 64: 101563


  • OBJECTIVE: Alterations in mitochondrial function play an important role in the development of various diseases, such as obesity, insulin resistance, steatohepatitis, atherosclerosis and cancer. However, accurate assessment of mitochondrial respiration ex vivo is limited and remains highly challenging. Using our novel method, we measured mitochondrial oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) of metabolically relevant tissues ex vivo to investigate the impact of different metabolic stressors on mitochondrial function. METHODS: Comparative analysis of OCR and ECAR in young mice fed either 12 weeks high-fat (HFD), high-sucrose (HSD), or western diet (WD), a HFD in matured mice, 2 years prolonged aging on standard-control diet (STD), as well as fasting in tissue biopsies. RESULTS: While diets had only marginal effects on mitochondrial respiration, respiratory chain complexes II and IV were reduced. Moreover, matured HFD-fed mice showed a decreased hepatic metabolic flexibility and prolonged aging increased OCR in brown adipose tissue. Interestingly, fasting boosted pancreatic and hepatic OCR while decreasing weight of those organs. Furthermore, ECAR measurements in adipose tissue could indicate its lipolytic capacity. CONCLUSION: Using ex vivo tissue measurements, we could extensively analyze mitochondrial function of liver, adipose tissue, pancreas and heart revealing effects of metabolic stress, especially aging.