Abstract P485: Exercise Influences Metabolic Parameters and Expression of Markers of Endoplasmic Reticulum Stress in a Diet-Dependent Manner

Abstract

The relationship between diet, exercise, and metabolic dysfunction is widely established; however the mechanisms responsible remain unclear. Endoplasmic reticulum stress (ERS) has been shown to play a significant role in metabolic homeostasis and disease processes; however it is unclear how diet and exercise interact to influence ERS. Therefore, the objective of this project was to determine how diet and exercise influence metabolic markers and mRNA expression of ERS-related genes. Weanling C57Bl/6 mice were randomly assigned to receive ad libitum access to standard laboratory chow, AIN93 diet, and our novel “Americanized” diet (AD) for 4-weeks. After 2-weeks, mice from each diet group were randomly assigned to exercise (n=7) or sedentary control groups (n=3). The exercise condition consisted of access to an exercise wheel, three times per week, for 16 hours per day. Wheel utilization was recorded using a bicycle computer/sensor. Insulin sensitivity was determined using standardized insulin-tolerance test. Mice were fasted, euthanized, and blood and liver tissues were collected. Circulating glucose and lipid levels were quantified and hepatic mRNA expression of genes related to ERS ( Ddit3 , Hspa5 , and Erdj4 ) were determined. Data were analyzed using GLM procedures in SPSS. Despite having no influence on body weight, diet (P=0.04) significantly influenced liver weight, with mice fed AD having greater (P = 0.01) liver weight compared to mice fed chow. Exercise tended to increase liver weight compared to the control (P=0.095), while reducing liver lipid content in mice fed chow and AD. AD fed mice had the highest circulating glucose values compared to mice fed chow (P=0.013) and also tended to be greater than mice fed AIN (P=0.056). Exercise significantly increased circulating triglycerides (P=0.03) and tended to reduce circulating glucose levels (P=0.07). Diet significantly influenced insulin sensitivity (P = 0.003), with mice fed AD having less insulin sensitivity as compared to mice fed chow (P<0.001) and also tended to be lower than mice fed AIN (P=0.06). While non-significant (P=0.15), exercising mice tended to have less insulin sensitivity than controls. Exercise caused an increase in Erdj4 mRNA expression (P=0.02), most notably in mice fed AD, which had a greater ER-stress response with exercise than other diet groups (P=0.04). Our data suggests that the physiological responses to acute exercise is dependent upon the quality of diet consumed, and these effects are associated with changes of markers of ERS. Additional studies are needed to further elucidate the mechanisms by which diet, exercise, and ERS interact to influence metabolic health.