Extracellular flux analyses reveal differences in mitochondrial PBMC metabolism between high-fit and low-fit females

Joëlle J.E. Janssen, Bart Lagerwaard, Mojtaba Porbahaie, Arie G. Nieuwenhuizen, Huub F.J. Savelkoul, R.J.J. van Neerven, Jaap Keijer, Vincent C.J. de Boer*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)


Analyzing metabolism of peripheral blood mononuclear cells (PBMCs) can possibly serve as a cellular metabolic read-out for lifestyle factors and lifestyle interventions. However, the impact of PBMC composition on PBMC metabolism is not yet clear, neither is the differential impact of a longer-term lifestyle factor versus a short-term lifestyle intervention. We investigated the effect of aerobic fitness level and a recent exercise bout on PBMC metabolism in females. PBMCs from 31 young female adults divided into a high-fit (V˙O2peak ≥ 47 mL/kg/min, n = 15) and low-fit (V˙O2peak ≤ 37 mL/kg/min, n = 16) groups were isolated at baseline and overnight after a single bout of exercise (60 min, 70% V˙O2peak). Oxygen consumption rate (OCR) and glycolytic rate (GR) were measured using extracellular flux (XF) assays and PBMC subsets were characterized using fluorescence-activated cell sorting (FACS). Basal OCR, FCCP-induced OCR, spare respiratory capacity, ATP-linked OCR, and proton leak were significantly higher in high-fit than in low-fit females (all P < 0.01), whereas no significant differences in glycolytic rate (GR) were found (all P > 0.05). A recent exercise bout did not significantly affect GR or OCR parameters (all P > 0.05). The overall PBMC composition was similar between high-fit and low-fit females. Mitochondrial PBMC function was significantly higher in PBMCs from high-fit than from lowfit females, which was unrelated to PBMC composition and not impacted by a recent bout of exercise. Our study reveals a link between PBMC metabolism and levels of aerobic fitness, increasing the relevance of PBMC metabolism as a marker to study the impact of lifestyle factors on human health.

Original languageEnglish
Pages (from-to)E141-E153
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number2
Publication statusPublished - Feb 2022


  • Aerobic fitness level
  • Biomarker
  • Lifestyle
  • Oxygen consumption rate
  • PBMC metabolism


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