, Volume 62, Issue 6, pp 1048–1064 | Cite as

Effects of long-term exercise on plasma adipokine levels and inflammation-related gene expression in subcutaneous adipose tissue in sedentary dysglycaemic, overweight men and sedentary normoglycaemic men of healthy weight

  • Sindre LeeEmail author
  • Frode Norheim
  • Torgrim M. Langleite
  • Hanne L. Gulseth
  • Kåre I. Birkeland
  • Christian A. Drevon



Obesity and insulin resistance may be associated with altered expression and secretion of adipokines. Physical activity can markedly improve insulin sensitivity, but the association with adipokines remains largely unknown. In this study, we examined the effects of physical activity on the subcutaneous white adipose tissue (scWAT) secretome and its relationship to insulin sensitivity.


As reported previously, we enrolled 26 sedentary, middle-aged men (13 dysglycaemic and overweight; 13 normoglycaemic and of healthy weight) into a 12 week, supervised, intensive physical exercise intervention that included two endurance and two resistance sessions each week. Insulin sensitivity was measured as the glucose infusion rate from a euglycaemic–hyperinsulinaemic clamp. In our previous study, we measured maximum oxygen uptake, upper- and lower-body strength and a range of circulating biomarkers, and quantified adipose tissue depots using MRI and magnetic resonance spectroscopy. We have now performed global mRNA sequencing, microarrays and RT-PCR of scWAT and skeletal muscle biopsies, and quantified selected plasma adipokines by ELISA.


Insulin sensitivity increased similarly in both dysglycaemic (45%) and normoglycaemic (38%) men after 12 weeks of exercise, as reported previously. mRNA sequencing of scWAT revealed 90 transcripts that responded to exercise in dysglycaemic men, whereas only marginal changes were observed in normoglycaemic men. These results were validated using microarrays and RT-PCR. A total of 62 out of 90 transcripts encoded secreted proteins. Overall, 17 transcripts were upregulated and 73 transcripts were downregulated. Downregulated transcripts included several macrophage markers, and were associated with inflammatory and immune-related pathways. Levels of these immune-related transcripts were enhanced in dysglycaemic men vs normoglycaemic men at baseline, but were normalised after the exercise intervention. Principal component and correlation analyses revealed inverse correlations between levels of these immune-related transcripts and insulin sensitivity at baseline, after the intervention, and for the change between baseline and after the intervention. In addition, levels of these transcripts at baseline could predict exercise-induced improvements in insulin sensitivity. Adipokine levels in scWAT (but not in skeletal muscle) were significantly correlated with corresponding plasma adipokine concentrations, as exemplified by leptin, high-molecular-weight adiponectin and secreted frizzled-related protein 4 (SFRP4). SFRP4 mRNA was the most exercise-responsive transcript in scWAT from dysglycaemic men, and plasma SFRP4 concentrations were reduced in dysglycaemic men, but not in normoglycaemic men, after 12 weeks of exercise.


This study indicates that scWAT may be an important mediator of exercise-induced improvements in insulin sensitivity, especially in overweight dysglycaemic individuals at increased risk of developing type 2 diabetes.


Adipokines Humans Insulin sensitivity Long-term exercise Prediabetes Subcutaneous adipose tissue 



Subcutaneous white adipose tissue


Glucose infusion rate


Magnetic resonance spectroscopy


Secreted frizzled-related protein 4

\( \dot{V}{\mathrm{O}}_{2\mathrm{max}} \)

Maximal oxygen uptake



We thank Å. Halsne, G. Vinje, K. E. Jahnsen, A. Heck, B. Nellemann (Department of Endocrinology, Oslo University Hospital), A. R. Enget (Department of Nutrition, University of Oslo), T. I. Gloppen, T. Dalen, H. Moen, M. A. Dahl, G. Grøthe, K. A Krog, Ø. Skattebo, E. Johansen, D. S. Tangen, K. K. Jensen, H. K. Stadheim, J. Jensen, E. N. Rise (Norwegian School of Sport Sciences) and the Norwegian Sequencing Centre.

Contribution statement

SL analysed and prepared the data, and wrote the first draft of the manuscript. All authors interpreted the data and reviewed, revised and approved the manuscript. KIB and CAD initiated, designed and supervised the study. CAD is the guarantor of this work.


This work was supported by grants from the Institute of Basic Medical Sciences, UiO, the Johan Throne-Holst Foundation for Nutrition Research, the Freia Medical Research Foundation, the ‘Functional Genomics’ and ‘Infrastructure’ programmes of the Research Council of Norway, the EU-financed FP7 project (NutriTech grant agreement no.: 289511) and the South-Eastern Regional Health Authorities.

Duality of interest

The authors declare that there is no duality of interest associated with this manuscript.

Supplementary material

125_2019_4866_MOESM1_ESM.pdf (394 kb)
ESM (PDF 394 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Sindre Lee
    • 1
    • 2
    Email author
  • Frode Norheim
    • 1
  • Torgrim M. Langleite
    • 1
  • Hanne L. Gulseth
    • 2
    • 3
  • Kåre I. Birkeland
    • 2
    • 4
  • Christian A. Drevon
    • 1
  1. 1.Department of Nutrition, Institute of Basic Medical Sciences, Faculty of MedicineUniversity of OsloOsloNorway
  2. 2.Department of Endocrinology, Morbid Obesity and Preventive MedicineOslo University HospitalOsloNorway
  3. 3.Department of Chronic Diseases and AgeingNorwegian Institute of Public HealthOsloNorway
  4. 4.Institute of Clinical Medicine, Faculty of MedicineUniversity of OsloOsloNorway

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