The Influence of Visfatin and Visfatin Gene Polymorphisms on Glucose and Obesity-related Variables and Their Responses to Aerobic Exercise Training

Title of Document: THE INFLUENCE OF VISFATIN AND VISFATIN GENE POLYMORPHISMS ON GLUCOSE AND OBESITY-RELATED VARIABLES AND THEIR RESPONSES TO AEROBIC EXERCISE TRAINING Jennifer Ann McKenzie, Ph.D., 2008 Directed By: Professor James M. Hagberg, Department of Kinesiology Adipokines, soluble factors produced by adipocytes, may help to connect diabetes and obesity; one such adipokine is visfatin. Previous research has linked visfatin and visfatin gene (PBEF1) polymorphisms with glucose and obesity-related conditions; however, less is known regarding visfatin’s response to an aerobic exercise training intervention, and no one, to our knowledge, has examined whether polymorphic variation in the PBEF1 gene affects aerobic exercise training-induced changes in glucose and obesity-related variables. Thus, this retrospective study investigated whether 6 months of aerobic exercise training reduced plasma visfatin levels in individuals with impaired glucose tolerance (IGT) or normal glucose tolerance (NGT). In addition, we examined the influence of common PBEF1 gene polymorphisms (-4689 G>T, -1543 C>T, -1001 T>G, -948 G>T, and SER301SER) and haplotypes on glucose and obesity-related variables and their responses to aerobic exercise training. Following the completion of 6 weeks of dietary stabilization, 116 healthy, sedentary, middle-aged, Caucasian men and women underwent 6 months of aerobic exercise training. Glucose total area under the curve (AUC), insulin AUC, and insulin sensitivity were measured via oral glucose tolerance tests. Plasma visfatin was measured using an enzyme immunoassay in 67 of the participants (22 with IGT, 45 with NGT), and standard techniques were used to assess lipoprotein-lipid and body composition variables. Restriction fragment length polymorphism techniques and TaqMan assays were used to determine PBEF1 genotypes. We found that plasma visfatin levels were comparable in IGT and NGT individuals at baseline and increased similarly in both groups in response to aerobic exercise training. We also found associations at baseline between glucose and obesityrelated variables and PBEF1 gene variants, with -4689, -1001, -948, and SER301SER variant allele groups and PBEF1 variant allele-containing haplotypes having higher insulin sensitivity. Last, PBEF1 genetic variation influenced the aerobic exercise training-induced change in glucose and obesity-related variables. Moreover, the -948 polymorphism, TCGTT haplotype, and TCGGT haplotype were associated with lipoprotein-lipid changes with training, and the SER301SER polymorphism influenced changes in BMI and body fat. Future studies need to address the functional significance of PBEF1 polymorphisms and haplotypes and clarify mechanisms connecting visfatin to glucose and obesity-related phenotypes. THE INFLUENCE OF VISFATIN AND VISFATIN GENE POLYMORPHISMS ON GLUCOSE AND OBESITY-RELATED PHENOTYPES AND THEIR RESPONSES TO AEROBIC EXERCISE TRAINING