title: 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.
abstract: OBJECTIVE
  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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Cardiology, Center for Clinical Heart Research, Oslo University Hospital, Ullevål, Oslo, Norway; Center for Heart Failure Research, Oslo University Hospital, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Ida Unhammer
authors.initials: IU
authors.lastname: Njerve
authors.affiliation: Department of Cardiology, Center for Clinical Heart Research, Oslo University Hospital, Ullevål, Oslo, Norway; Center for Heart Failure Research, Oslo University Hospital, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Rune
authors.initials: R
authors.lastname: Byrkjeland
authors.affiliation: Department of Cardiology, Center for Clinical Heart Research, Oslo University Hospital, Ullevål, Oslo, Norway; Center for Heart Failure Research, Oslo University Hospital, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Harald
authors.initials: H
authors.lastname: Arnesen
authors.affiliation: Department of Cardiology, Center for Clinical Heart Research, Oslo University Hospital, Ullevål, Oslo, Norway; Center for Heart Failure Research, Oslo University Hospital, Oslo, Norway.
authors.forename: Sissel
authors.initials: S
authors.lastname: Åkra
authors.affiliation: Department of Cardiology, Center for Clinical Heart Research, Oslo University Hospital, Ullevål, Oslo, Norway; Center for Heart Failure Research, Oslo University Hospital, Oslo, Norway.
authors.forename: Svein
authors.initials: S
authors.lastname: Solheim
authors.affiliation: Department of Cardiology, Center for Clinical Heart Research, Oslo University Hospital, Ullevål, Oslo, Norway; Center for Heart Failure Research, Oslo University Hospital, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Ingebjørg
authors.initials: I
authors.lastname: Seljeflot
keywords: MCP-1; coronary artery disease; diabetes; exercise; fractalkine (CX3CL1); subcutaneous adipose tissue