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Effects of long-term exercise training on adipose tissue expression of fractalkine and MCP-1 in patients with type 2 diabetes and stable coronary artery disease: a substudy of a randomized controlled trial

Authors Njerve I, Byrkjeland R, Arnesen H, Åkra S, Solheim S, Seljeflot I

Received 13 September 2015

Accepted for publication 23 November 2015

Published 14 March 2016 Volume 2016:9 Pages 55—62

DOI https://doi.org/10.2147/DMSO.S96299

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Alfonso Eirin

Peer reviewer comments 3

Editor who approved publication: Professor Ming-Hui Zou


Ida Unhammer Njerve,1–3 Rune Byrkjeland,1–3 Harald Arnesen,1–3 Sissel Åkra,1,2 Svein Solheim,1,2 Ingebjørg Seljeflot1–3

1Department of Cardiology, Center for Clinical Heart Research, Oslo University Hospital, Ullevål, 2Center for Heart Failure Research, Oslo University Hospital, 3Faculty of Medicine, University of Oslo, Oslo, Norway

Purpose: Adipose tissue inflammation plays a role in atherosclerosis and type 2 diabetes (T2DM). We aimed to investigate whether 12 months of exercise training in patients with both T2DM and coronary artery disease (CAD) reduced the genetic expression of the proinflammatory markers fractalkine (CX3CL1) and its receptor (CX3CR1) and monocyte chemoattractant protein-1 (MCP-1) in the subcutaneous adipose tissue. Expression of the genes in the circulating leukocytes and circulating levels of the markers were also investigated.
Patients and methods: A total of 137 patients with T2DM and CAD were included to study the effects of exercise on atherosclerosis progression and glucose control. Patients were randomized to exercise training (combined aerobic and strength training) or control. At inclusion and after 12 months, fasting blood samples and a subcutaneous adipose tissue sample were taken. RNA was extracted from the adipose tissue and circulating leukocytes, and the expression levels were examined by reverse transcription-polymerase chain reaction. Circulating fractalkine and MCP-1 were determined by enzyme-linked immunosorbent assay.
Results: The analyses were performed in 114 patients who completed the study and adhered to the intervention principle. At baseline, gene expression of fractalkine and CX3CR1 in the adipose tissue was similar in the two groups. There were no change within either group and no between-group differences in changes from baseline. Circulating fractalkine increased after 12 months in the exercise group (P=0.044), significantly more compared to controls (P=0.042), however only in the patients with advanced vascular disease. Neither the expression levels of MCP-1 nor the circulating levels changed significantly in either group. At baseline, CX3CR1 expression in the adipose tissue was associated with body mass index (P<0.001).
Conclusion: No significant effects of long-term exercise training on adipose tissue expression of fractalkine, CX3CR1, or MCP-1 were found in our patients with combined CAD and T2DM. However, a slight increase in circulating fractalkine after the intervention was recorded. The association of CX3CR1 expression with body mass index might indicate increased immune activation in the adipose tissue.

Keywords: diabetes, coronary artery disease, subcutaneous adipose tissue, exercise, MCP-1, fractalkine (CX3CL1)

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