Irisin was first identified as a peroxisome proliferator-activated receptor γ co-activator-1α (PGC-1α) dependent myokine with the potential to induce brown fat development in white adipose tissue through thermogenesis via increased uncoupling protein 1 (UCP-1). The recent discovery of irisin secretion during exercise from its larger segment fibronectin type III domain-containing protein 5 (FNDC5) as well as increased FNDC5/irisin levels in diseased states of obesity and type II diabetes mellitus from adipose postulate an important finding with regard to this unsolved mechanism. However, the effects that a high fat diet, chronic exercise, and pre-diabetes in mice has not been fully elucidated.
Purpose: To evaluate the effects that a high fat diet and exercise have on FNDC5 and its associated proteins in skeletal muscle and adipose tissue in pre-diabetic male, C57BL/6 mice.
Methods: Experiments were performed on frozen tissues that were harvested from a previous intervention at the University of Kansas Medical Center. Male seven week-old C57BL/6 mice were placed on a 12:12 light dark cycle with ad libitum access to food and water and randomized to one of three groups: standard diet, sedentary (Std) (14% kcals from fat), high fat diet, sedentary (HF) (54% kcals from fat), or high fat diet, exercise (HFEX) (54% kcals from fat) for the entire 4 weeks of the study. Half of the mice on HF diet were randomly assigned to an exercise group where they were caged individually and had ad libitum access to a running wheel for the duration of the study. Plasma samples were obtained following a three hour fast for insulin and glucose levels and the homeostatic model assessment of insulin resistance (HOMA-IR) was used to calculate insulin resistance. Following the 4 week study, mice were sacrificed 24 hours after final exercise session to eliminate acute effects of exercise. Gastrocnemius skeletal muscle and epididymal adipose tissue were harvested and stored. Data were presented as a means ± SEM. Data was analyzed by a one factor analysis of variance (ANOVA). Fisher’s test of least square difference post-hoc comparisons was used if significant effects were observed, to identify significant differences between groups. Statistical significance was set at P < 0.05.
Results: Body weight, glucose, insulin, and HOMA-IR were significantly higher in HF (P<0.001) compared to Std and HFEX after 4-week intervention. Exercise in HFEX group helped prevent excess weight gain as well as prevented increase in serum insulin levels and HOMA-IR in high-fat fed mice. HFEX group experienced a reduction in fasting blood glucose levels during the experiment while HF group saw dramatic increase in fasting blood glucose (P<0.001). Serum insulin, as well as HOMA-IR levels were significantly higher in the HF group compared to the Std group (P<0.05) and HFEX group (P<0.01). Skeletal muscle FNDC5 protein levels showed no significant difference among Std, HF, or HFEX groups. However, there was a trend (p=0.09) towards increased FNDC5 in the HF group compared to the HFEX group. UCP-1 levels were found to be significantly lower in the HFEX group compared to the Std group (P<0.05). There was no significant difference in PGC-1? among groups. Adipose levels of FNDC5 were found to have no significant difference among groups. Adipose UCP-1 levels were also found to have no significant difference among groups. PGC-1? was not detectable in adipose tissue. Muscle FNDC5 protein levels from all groups, Std, HF, and HFEX displayed no correlation with glucose. Adipose FNDC5 protein levels displayed no correlation in either Std nor HF group. However, a correlation was found (p<0.025) in adipose FNDC5 and glucose in HFEX group.
Conclusion: Exercise in a group of mice fed a high fat diet led to improvements in bodyweight, glucose, insulin, and HOMA-IR. A correlation was found (p<0.025) in adipose FNDC5 and glucose in HFEX group. There was a trend towards increased FNDC5 levels (p=0.09) in skeletal muscle of high-fat fed, pre-diabetic mice in comparison with high-fat fed mice performing chronic endurance training. These findings suggest that FNDC5/irisin and its associated proteins may play a role in exercise and energy regulation in atypical metabolic states such as obesity and insulin resistance.
|Commitee:||Gopalan, Chaya, Wooten, Joshua|
|School:||Southern Illinois University at Edwardsville|
|Department:||Kinesiology and Health Education|
|School Location:||United States -- Illinois|
|Source:||MAI 55/05M(E), Masters Abstracts International|
|Subjects:||Endocrinology, Nutrition, Kinesiology, Physiology|
|Keywords:||Exercise, Fibronectin type III domain-containing protein 5, Irisin, PGC-1alpha, Pre-diabetes, Uncoupling protein 1|
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