Endothelium-derived factors influence differentiation of fat-derived stromal cells post-exercise in subjects with prediabetes

Nabanita Kundu, Cleyton C. Domingues, Eric S. Nylen, Edina Paal, Peter Kokkinos, Sabyasachi Sen

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Purpose: We investigated the effect of aerobic and resistance exercise on abdominal subcutaneous fat-derived stromal cells in middle-Aged subjects with prediabetes, pre-and post-exercise to establish molecular mechanisms that drive the effect of exercise. Methods: Five subjects, aged between 40 and 60 years with a body mass index between 25 and 39.9 kg/m2 and with prediabetes, were enrolled in a 12-week exercise intervention program. Biophysical parameters were assessed pre-and post-exercise. Stromal cells were obtained from subcutaneous abdominal fat and cultured for 2-3 weeks. The stromal cells were then analyzed for mRNA analysis pre-and post-exercise. This was followed up with in vitro experiments where commercially obtained human fat-derived mesenchymal stromal cells (MSCs) were exposed to adipogenic media, and conditioned media from human endothelial conditioned media (ECM) cells were added to note if ECM addition altered adipogenesis. Subsequently, MSC differentiation was monitored by reverse transcription-polymerase chain reaction (RT-PCR). Results: Post-exercise, subjects' cardiometabolic parameters improved. MSC obtained at post-exercise phase, from subcutaneous fat biopsies, on RT-PCR analysis, showed upregulation of antioxidant, mitochondrial, glucose transporter, and genes associated with osteogenesis compared with pre-exercise MSC mRNA. A concomitant increase in plasma osteocalcin levels was also noted post-exercise. In vitro, MSCs exposed to adipogenic differentiation media with the addition of ECM showed a significant reduction in expression of adipogenic marker genes and instead showed upregulation of genes associated with osteogenic differentiation. Conclusions: Exercise appears to prevent adipogenic differentiation of fat-derived stromal cells and promote osteogenic differentiation, in prediabetic middle-Aged subjects. Interestingly, the addition of endothelium-derived factors to adipogenic media also appears to prevent adipogenic differentiation of commercially obtained fat-derived stromal cells and promotes osteogenic differentiation. Both in vivo and in vitro findings emphasize the paracrine effect of endothelium-derived factors on fat differentiation.

Original languageEnglish (US)
Pages (from-to)314-322
Number of pages9
JournalMetabolic Syndrome and Related Disorders
Issue number6
StatePublished - Jul 1 2019
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism


  • exercise
  • fat biopsy
  • prediabetes
  • stromal vascular fraction


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