Active Voice: Physical Activity, Sedentary Behavior and Estrogen Metabolism — Where Do We Stand?

By Inga Bae-Gartz, M.D. and Eva Hucklenbruch-Rother, M.D., Ph.D.
Inga Bae-Gartz, M.D. Eva Hucklenbruch-Rother, M.D., Ph.D.

Viewpoints presented in SMB commentaries represent opinions of the authors and do not necessarily represent positions or policies of ACSM.

Inga Bae-Gartz, M.D., is a pediatrician at the University Hospital of Cologne, Germany. She is working as a post-doc in the field of perinatal programming. Her research focuses on maternal factors during pregnancy and early life and the effects to the offspring, with special emphasis on maternal exercise in lean and obese pregnancies.

Eva Hucklenbruch-Rother, M.D., Ph.D., is a pediatrician who earned her Ph.D. investigating the mechanisms of hypothalamic regulation of energy homeostasis in mice. Her current research focuses on maternal and environmental factors during pregnancy and early life, and on the short- and long-term effects on the offspring’s health, with special emphasis on the brain.

This commentary presents the authors’ views on the topic of a research article which they and their colleagues had published in the May 2016 issue of
Medicine & Science in Sports & Exercise® (MSSE).

Despite tremendous efforts to develop effective prevention and treatment strategies, obesity prevalence is still on the rise. Obesity causes a variety of sequelae that challenge health care systems, but most importantly are those that burden the individual. We have learned that obesity of the mother can be a serious risk factor for the development of obesity in the child. This can be partially attributed to the family’s shared environment, but studies in mice and humans also have established that strong links exist between maternal nutrition, body composition and exercise routines – these prevail both before and during pregnancy and lactation and impact the child’s subsequent health. With regard to the brain, one important finding is mal-programming of hunger- and satiety-regulating neurocircuits in the mediobasal hypothalamus of the child as a consequence of maternal obesity.

In our studies with mouse models, as reported in the May 2016 issue of MSSE, we tested preventive strategies in maternal diet-induced obesity and evaluated the impact of these strategies on deteriorative molecular mechanisms in the offspring. We found that voluntary wheel running during pregnancy in obese mouse dams reduced the risk for disturbed glucose metabolism in the offspring by preventing pro-inflammatory processes in the hypothalamus.

In detail, at the end of the lactation, offspring of obese mothers show an almost four-fold increase in serum IL-6 with clear activation of STAT3 (Signal transducer and activator of transcription 3) signaling in white adipose tissue and hypothalamus; however, these changes were completely blunted by maternal exercise during pregnancy. Interestingly, maternal obesity predominantly increased pro-inflammatory IL-6 “Trans-signaling,” whereas classical, regenerative and anti-inflammatory IL-6 signaling in the liver was adversely influenced. Offspring of exercised obese dams were protected against these changes. Furthermore, altered hypothalamic global gene expression shows partial normalization after maternal exercise, especially with respect to IL-6 action and neurogenesis.

While a growing number of animal studies have demonstrated long-lasting, preventive effects of maternal exercise on the offspring’s body weight and glucose metabolism, data on these exercise outcomes in obese women is very limited. The human interventional studies, to date, have focused on maternal and obstetrical outcome parameters, neglecting short- and long-term effects on the child. Moreover, the compliance of obese mothers to standardized exercise programs seems to be relatively low.

Only recently, Lenoir-Wijnkoop and colleagues estimated that the medical costs of maternal overweight and related overweight in the offspring amount to more than $1.8 billion per year in the U.S. This fact alone should be sufficient to underline the importance of the ongoing research in this field – research aimed toward determining how best to prevent perinatal programming of obesity. By delivering profound evidence from animal studies like ours which demonstrated positive effects of maternal exercise on offspring, we hope to increase acceptance and enthusiasm among obese pregnant women for appropriate exercise programs.

Offering expectant mothers a realistic, preventive tool to break the vicious cycle of obesity and allow their children to start life without a metabolic burden is the major motivation behind our work.