title: Insulin-resistant subjects have normal angiogenic response to aerobic exercise training in skeletal muscle, but not in adipose tissue.
abstract: Reduced vessel density in adipose tissue and skeletal muscle is associated with obesity and may result in decreased perfusion, decreased oxygen consumption, and insulin resistance. In the presence of VEGFA, Angiopoietin-2 (Angpt2) and Angiopoietin-1 (Angpt1) are central determinants of angiogenesis, with greater Angpt2:Angpt1 ratios promoting angiogenesis. In skeletal muscle, exercise training stimulates angiogenesis and modulates transcription of VEGFA, Angpt1, and Angpt2. However, it remains unknown whether exercise training stimulates vessel growth in human adipose tissue, and it remains unknown whether adipose angiogenesis is mediated by angiopoietin signaling. We sought to determine whether insulin-resistant subjects would display an impaired angiogenic response to aerobic exercise training. Insulin-sensitive (IS, N = 12) and insulin-resistant (IR, N = 14) subjects had subcutaneous adipose and muscle (vastus lateralis) biopsies before and after 12 weeks of cycle ergometer training. In both tissues, we measured vessels and expression of pro-angiogenic genes. Exercise training did not increase insulin sensitivity in IR Subjects. In skeletal muscle, training resulted in increased vessels/muscle fiber and increased Angpt2:Angpt1 ratio in both IR and IS subjects. However, in adipose, exercise training only induced angiogenesis in IS subjects, likely due to chronic suppression of VEGFA expression in IR subjects. These results indicate that skeletal muscle of IR subjects exhibits a normal angiogenic response to exercise training. However, the same training regimen is insufficient to induce angiogenesis in adipose tissue of IR subjects, which may help to explain why we did not observe improved insulin sensitivity following aerobic training.
authors.affiliation: College of Health Sciences, University of Kentucky, Lexington, Kentucky.
authors.forename: R Grace
authors.initials: RG
authors.lastname: Walton
authors.affiliation: The Department of Medicine, Division of Endocrinology, and the Barnstable Brown Diabetes and Obesity Center, University of Kentucky, Lexington, Kentucky.
authors.forename: Brian S
authors.initials: BS
authors.lastname: Finlin
authors.affiliation: College of Health Sciences, University of Kentucky, Lexington, Kentucky.
authors.forename: Jyothi
authors.initials: J
authors.lastname: Mula
authors.affiliation: College of Health Sciences, University of Kentucky, Lexington, Kentucky.
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Long
authors.affiliation: The Department of Medicine, Division of Endocrinology, and the Barnstable Brown Diabetes and Obesity Center, University of Kentucky, Lexington, Kentucky.
authors.forename: Beibei
authors.initials: B
authors.lastname: Zhu
authors.affiliation: College of Health Sciences, University of Kentucky, Lexington, Kentucky.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Fry
authors.affiliation: Department of Biostatistics, College of Public Health, University of Kentucky, Lexington, Kentucky.
authors.forename: Philip M
authors.initials: PM
authors.lastname: Westgate
authors.affiliation: College of Health Sciences, University of Kentucky, Lexington, Kentucky.
authors.forename: Jonah D
authors.initials: JD
authors.lastname: Lee
authors.affiliation: Division of Physician Assistant Studies, College of Health Sciences, University of Kentucky, Lexington, Kentucky.
authors.forename: Tamara
authors.initials: T
authors.lastname: Bennett
authors.affiliation: The Department of Medicine, Division of Endocrinology, and the Barnstable Brown Diabetes and Obesity Center, University of Kentucky, Lexington, Kentucky.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Kern
authors.affiliation: College of Health Sciences, University of Kentucky, Lexington, Kentucky cpete4@uky.edu.
authors.forename: Charlotte A
authors.initials: CA
authors.lastname: Peterson
keywords: Angiogenesis; angiopoietins; exercise; insulin resistance