Running Exercise in Obese Pregnancies Prevents IL-6 Trans-signaling in Male Offspring

PURPOSE: Maternal obesity is known to predispose the offspring for the development of impaired glucose metabolism and obesity associated with low-grade inflammation and hypothalamic dysfunction. Since preventive approaches in this context are missing to date, we aimed to identify molecular mechanisms in the offspring that are affected by maternal exercise during pregnancy.

METHODS: Diet-induced obese mouse dams were divided in a sedentary obese (HFD) and an obese intervention group (HFD-RUN), which performed voluntary wheel running throughout gestation. Male offspring were compared to the offspring of a sedentary lean control group (CO) at postnatal day 21.

RESULTS: HFD and HFD-RUN offspring showed increased body weight and white adipose tissue (WAT) mass. Glucose tolerance testing showed mild impairment only in HFD offspring. Serum IL-6 (Interleukin-6) levels, hypothalamic and WAT IL-6 gene expression, and phosphorylation of STAT3 (Signal transducer and activator of transcription 3) in HFD offspring were significantly increased, whereas HFD-RUN was protected against these changes. Altered hypothalamic global gene expression in HFD offspring showed partial normalization in HFD-RUN offspring especially with respect to IL-6 action.

CONCLUSION: Thus, maternal exercise in obese pregnancies effectively reduces IL-6 trans-signaling and might be one underlying mechanism for the amelioration in glucose metabolism at P21 independent of body composition.