Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2018 Aug;10(8):1033-1050.
doi: 10.2217/epi-2018-0039. Epub 2018 Apr 19.

Exercise training alters the genomic response to acute exercise in human adipose tissue

Odile Fabre  1 , Lars R Ingerslev  1 , Christian Garde  1 , Ida Donkin  1 , David Simar  2 , Romain Barrès  1
Affiliations
Clinical Trial

Exercise training alters the genomic response to acute exercise in human adipose tissue

Odile Fabre et al. Epigenomics. 2018 Aug.

Abstract

Aim: To determine the genomic mechanisms by which adipose tissue responds to acute and chronic exercise.

Methods: We profiled the transcriptomic and epigenetic response to acute exercise in human adipose tissue collected before and after endurance training.

Results: Although acute exercises were performed at same relative intensities, the magnitude of transcriptomic changes after acute exercise was reduced by endurance training. DNA methylation remodeling induced by acute exercise was more prominent in trained versus untrained state. We found an overlap between gene expression and DNA methylation changes after acute exercise for 32 genes pre-training and six post-training, notably at adipocyte-specific genes.

Conclusion: Training status differentially affects the epigenetic and transcriptomic response to acute exercise in human adipose tissue.

Keywords: DNA methylation; adipose tissue; epigenetics; exercise; human; mRNA; transcriptomic.

PubMed Disclaimer

Conflict of interest statement

Financial & competing interests disclosure

This study makes use of data generated by the BLUEPRINT Consortium. A full list of the investigators who contributed to the generation of the data is available from www.blueprint-epigenome.eu. Funding for the project was provided by the European Union's Seventh Framework Programme (FP7/2007–2013) under grant agreement no 282510 – BLUEPRINT. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Figures

<b>Figure 1.</b>
Figure 1.. Workflow of the study.
The 15 male volunteers first performed an intense (80% VO2 max) 15-min exercise bout on an electromagnetically-braked cycle ergometer. sWATs were collected under fasting conditions at rest (basal), 20 min (20′), 1 h (60′) and 4 h (240′) after cessation of exercise. This entire procedure was repeated after the subjects had performed a 6-week intensive (75–85% VO2 max) exercise program (45-min spinning classes, 5 days per week) at least 5 days after the last training session. sWAT: Subcutaneous white adipose tissue; VO2 max: Maximal oxygen consumption.
<b>Figure 2.</b>
Figure 2.. Transcriptomic changes induced by acute exercise in human subcutaneous white adipose tissue (RNA sequencing).
(A) PCA of RNA-seq data for the major two PCs. The 95% confidence ellipses are shown for each group. (B) Heatmaps of the differentially expressed genes in adipose tissue before (basal) and after (240′) the acute exercise bout, before (pretraining) or after (post-training) the 6-week exercise training program. FDR <0.1. (C) Venn diagram representing the number of genes that were upregulated or downregulated after the acute exercise bout, before (pre-training) and after (post-training) the 6-week exercise training program. The intersection represents genes that were regulated in both conditions. FDR <0.1. (D) Gene ontology analysis (biological process) of differentially expressed genes after acute exercise, before (pre-training) and after (post-training) the exercise training intervention. FDR <0.1. FDR: False discovery rate; PC: Principal component; PCA: Principal component analysis; RNA-seq: RNA sequencing; sWAT: Subcutaneous white adipose tissue.
<b>Figure 3.</b>
Figure 3.. Modulation of the immune/inflammatory response induced by acute exercise with exercise training.
(A) Representation of the variation in the fold change of expression induced by acute exercise of the 285 genes differentially expressed in both pre- and post-training conditions between these two time points. FDR <0.1. (B) Gene ontology analysis (biological process) of the 285 genes that were differentially expressed after acute exercise in both pre- and post-training conditions. FDR <0.1. FDR: False discovery rate.
<b>Figure 4.</b>
Figure 4.. Evaluation of monocyte/macrophage infiltration induced by acute exercise and its impact on RNA sequencing data.
(A) RT-qPCR analysis of CD14 (n = 12), CD68 (n = 12) and HBB (n = 10) mRNA expression in adipose tissue biopsies collected at basal time (basal) and 4 h (240′) after acute exercise, before (pre-training) and after (post-training) the exercise training program. *p = 0.021 for CD14 and *p = 0.011 for CD68 240′ versus basal, pretraining. All graphs represent 2-ΔCt values expressed relatively to the mean of pretraining 2-ΔCt values obtained for all subjects, which was set at 1. Vertical axis scale is logarithmic base 10. (B) Volcano plots showing directional changes of the differentially expressed genes in adipose tissue after the acute exercise bout, before (pre-training) or after (post-training) the 6-week exercise training program. The genes differentially expressed due to immune cell infiltration (black dots) and those related to changes in adipocyte functions (red dots) are shown. FDR <0.1. (C) Gene ontology analysis (Biological Process) of the adipocyte-related genes that were differentially expressed after acute exercise in both pre- (blue) and post-training (red) conditions. FDR <0.1. FDR: False discovery rate; qPCR: Quantitative PCR; RNA-seq: RNA sequencing.
<b>Figure 5.</b>
Figure 5.. DNA methylation changes induced by acute exercise in human subcutaneous white adipose tissue reduced representation bisulfite sequencing.
(A) DMR location in relation to the nearest gene. (B) Validation of RRBS results by visualization of the representation of highly- and lowly-methylated sequences (information obtained from the Epigenome Roadmap) across samples. (C) PCA of RRBS data for the major two PCs. The 95% confidence ellipses are shown for each group. DMR: Differentially methylated region; PC: Principal component; PCA: Principal component analysis; RRBS: Reduced representation bisulfite sequencing; sWAT: Subcutaneous white adipose tissue.
<b>Figure 6.</b>
Figure 6.. Evaluation of monocyte/macrophage infiltration induced by acute exercise and its impact on reduced representation bisulfite sequencing data.
(A) qPCR analysis of HBB (n = 8) and CD14 (n = 8) mRNA expression in adipose tissue biopsies collected at basal time (basal), 20 min (20′), 1 h (60′) and 4 h (240′) after acute exercise, before (pretraining) or after (post-training) the exercise training program. All graphs represent 2-ΔCt values expressed relatively to the mean of pretraining 2-ΔCt values obtained for all subjects, which was set at 1. Vertical axis scale is logarithmic base 10. (B) Estimated macrophage infiltration at 20, 60 and 240 min after an acute bout of exercise, before (pretraining) or after (post-training) the exercise training program. A fraction of 0 would represent tissue no more infiltrated than at rest, while a fraction of 1 would be a pure macrophage sample. Connected point belong to the same participant. (C) Volcano plots showing directional changes of the DMRs in adipose tissue after the acute exercise bout, before (pretraining) or after (post-training) the 6-week exercise training program. The regions differentially methylated due to immune cell infiltration (black dots) and those related to changes in adipocyte functions (red dots) are shown. FDR <0.1. DMR: Differentially methylated region; qPCR: Quantitative PCR; RRBS: Reduced representation bisulfite sequencing.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Frayn KN. Fat as a fuel: emerging understanding of the adipose tissue–skeletal muscle axis. Acta Physiol. 2010;199(4):509–518. - PubMed
    1. Stallknecht B, Dela F, Helge JW. Are blood flow and lipolysis in subcutaneous adipose tissue influenced by contractions in adjacent muscles in humans? Am. J. Physiol. Endocrinol. Metab. 2007;292(2):E394–E399. - PubMed
    1. Crampes F, Beauville M, Riviere D, Garrigues M. Effect of physical training in humans on the response of isolated fat cells to epinephrine. J. Appl. Physiol. 1986;61(1):25–29. - PubMed
    1. Crampes F, Beauville M, Riviere D, Garrigues M, Lafontan M. Lack of desensitization of catecholamine-induced lipolysis in fat cells from trained and sedentary women after physical exercise. J. Clin. Endocrinol. Metab. 1988;67(5):1011–1017. - PubMed
    1. Ronn T, Volkov P, Tornberg A, et al. Extensive changes in the transcriptional profile of human adipose tissue including genes involved in oxidative phosphorylation after a 6-month exercise intervention. Acta Physiol. 2014;211(1):188–200. - PubMed

    2. •• Exercise induces extensive transcriptomic changes in human adipose tissue, notably in the expression of genes involved in oxidative phosphorylation and many metabolic pathways.

Publication types