Paternal Exercise Improves Glucose Metabolism in Adult Offspring

Abstract

Poor paternal diet has emerged as a risk factor for metabolic disease in offspring, and alterations in sperm may be a major mechanism mediating these detrimental effects of diet. Although exercise in the general population is known to improve health, the effects of paternal exercise on sperm and offspring metabolic health are largely unknown. Here, we studied 7-week-old C57BL/6 male mice fed a chow or high-fat diet and housed either in static cages (sedentary) or cages with attached running wheels (exercise trained). After 3 weeks, one cohort of males was sacrificed and cauda sperm obtained, while the other cohort was bred with chow-fed sedentary C57BL/6 females. Offspring were chow fed, sedentary, and studied during the first year of life. We found that high-fat feeding of sires impairs glucose tolerance and increases the percentage of fat mass in both male and female offspring at 52 weeks of age. Strikingly, paternal exercise suppresses the effects of paternal high-fat diet on offspring, reversing the observed impairment in glucose tolerance, percentage of fat mass, and glucose uptake in skeletal muscles of the offspring. These changes in offspring phenotype are accompanied by changes in sperm physiology, as, for example, high-fat feeding results in decreased sperm motility, an effect normalized in males subject to exercise training. Deep sequencing of sperm reveals pronounced effects of exercise training on multiple classes of small RNAs, as multiple changes to the sperm RNA payload observed in animals consuming a high-fat diet are suppressed by exercise training. Thus, voluntary exercise training of male mice results in pronounced improvements in the metabolic health of adult male and female offspring. We provide the first in-depth analysis of small RNAs in sperm from exercise-trained males, revealing a marked change in the levels of multiple small RNAs with the potential to alter phenotypes in the next generation.

Exercise during pregnancy mitigates the adverse effects of maternal obesity on adult male offspring vascular function and alters one‐carbon metabolism

“…We chose this approach to avoid stress associated with forced exercise protocols in the dams. Recent studies have reported that paternal exercise (>3 weeks) can mitigate the detrimental effects of paternal obesity on offspring glucose tolerance, adiposity, and pancreatic β-cell mass; vascular function was not assessed (McPherson, Lane, Sandeman, Owens, & Fullston, 2017;McPherson, Owens, Fullston, & Lane, 2015;Stanford et al, 2018). In our study, the mating pairs were set up nightly and males were removed immediately after breeding was confirmed (visible by a vaginal plug).…”

Sperm RNA code programmes the metabolic health of offspring

“…For example, the sperm RNA signature could be used as a clinical marker of offspring metabolic disease susceptibility. In addition, as human sperm RNA profiles are known to be efficiently altered by improved body condition 1,[83][84][85] , the signature could be monitored before a planned pregnancy and clinical guidance (such as improvements to lifestyle) could also be introduced if necessary to reshape the sperm RNA code towards a healthy condition (Fig. 3).…”

Much to HAPO FUS About: Increasing Maternal Glycemia in Pregnancy Is Associated With Worsening Childhood Glucose Metabolism

“…The optimal time period(s) to intervene to reduce offspring metabolic risk needs further study (i.e., treatment of pregnant mothers, treatment of affected infants, children, or youth, or a multifaceted approach). Other possible mechanisms should be studied to assess their possible contribution to offspring metabolic outcomes in relation to maternal hyperglycemia, including shared genetics, shared environmentdsimilar diets and exercise patterns as well as chemical exposures (20)dand paternal effects (21,22). Still, with childhood obesity, metabolic disease, and type 2 diabetes being challenging conditions to treat successfully, any interventions that may prevent their emergence should be strongly considered by professional societies and clinicians.…”