Short Orals: Health outcomes

BACKGROUND: The rates of obesity increase world-wide, including women of child-bearing age, thus, it is critical to develop strategies to prevent the intergenerational cycle of obesity. Data suggests that gestational exercise positively influences pregnancy and birth outcomes. However, it is unknown how exercise metrics influences these outcomes and whether it improves outcomes at the cell and whole-body level.
PURPOSE: To elucidate the influence of exercise metrics (frequency, intensity, time, type, volume) during pregnancy on birth and infant outcomes at the cell and whole body level. We hypothesized that increased exercise volume throughout pregnancy would positively influence birth & infant health at the cell and whole-body level.
METHODS: We measured placentas at delivery. We used mesenchymal stem cells (MSCs) from umbilical cords at birth, and body morphometry at 1-month of age; women did supervised exercise for 24+ weeks of pregnancy; all exercise metrics were recorded.
RESULTS: We demonstrated that increased maternal exercise duration throughout pregnancy as well as weekly and total exercise volume improve placenta health and birth outcomes, even in preterm deliveries. Similarly, we found that increased maternal duration throughout pregnancy as well as weekly and total exercise volume improves infant cellular metabolism and decrease one-month body fat percent.
PRACTICAL IMPLICATIONS: Our data suggests that more maternal exercise is protective and leads to improved pregnancy, placental, and birth outcomes; changes in pregnancy could decrease the propensity to develop poor outcomes as well as obesity and associated metabolic conditions later in life.
Funding: American Heart Association

Background:
Low physical activity (PA) levels are associated with increased mortality. Improved measurement via accelerometery has shown a stronger association between PA and all-cause mortality compared with self-reported survey data, but this has not yet been translated to estimates of the population level disease burden attributable to low PA.

Purpose:
To estimate by how much low physical activity reduces life expectancy, and how much lifetime could be gained by increasing physical activity levels for both populations and individuals.

Methods:
We used device-measured physical activity risk estimates of all-cause mortality and a lifetable model analysis to construct a model of the 2019 American population aged 40+ years. Mortality data were from the National Centre for Health Statistics, 2017.

Results:
If all were as active as the top 25% of the population, Americans over the age 40 could expect to live an extra 5.3 years (95% uncertainty interval 3.7 to 6.8) on average. The greatest average gain in lifetime per single hour of walking was seen for individuals in the lowest activity quartile, where a one-hour walk could add 376.3 minutes (~6.3 hours) to life expectancy (95% uncertainty interval 321.5 to 428.5 minutes), on average.

Conclusions:
Physical activity provides substantially larger health benefits than previously thought.

Practical implications:
Increased investment in physical activity promotion and creating physical activity promoting living environments can yield large health gains.

Funding:
Previous funding from the New South Wales Ministry of Health, Sydney, Australia, is gratefully acknowledged.

Background: Physical inactivity is a global health concern and causes more than five million premature deaths annually. Although heritability estimates suggest a strong genetic influence on physical activity, genome-wide association studies have reported weak associations involving few genetic variants. Partly because physical activity is a complex phenotypic trait that is difficult to accurately capture.

Purpose: To identify genetic variation associated with different aspects of device-measured moderate to vigorous physical activity, such as average minutes of brisk walking or running per day and accumulated bouts of at least 10 or 30 consecutive minutes.

Methods: In HUNT4, 26,159 participants had at least one valid day of device-measured physical activity and genotyping of good quality. Machine-learning was used to classify every five seconds of activity into moderate walking, brisk walking, running, or cycling. This was accumulated into average minutes per day of ‘moderate to vigorous activity’ or ‘brisk walking or running’, and in consecutive bouts of at least 10 or 30 minutes. REGINIE was used to analyze genome-wide association with significance threshold of 5×10^-8. Follow-up analyzes included LD-score regression, ANNOVAR and GTEx to annotate plausible gene and tissue-expressions.

Results: One genetic locus was associated with 10-minute bouts of moderate to vigorous activity, whereas two loci were associated with brisk walking or running in 30-minute bouts. For the latter phenotype, the lead genetic variant rs111388372 on chromosome 4 is located within the GATB gene that are involved in oxidative phosphorylation and is generally expressed across tissues.

Conclusion: Three genetic loci was associated with bouts of continuous moderate to vigorous physical activity, with GATB as a candidate gene.

Practical implications: Genetic variation associated with physical activity provides biological insight into possible mechanisms and may contribute to genetic instruments applicable in Mendelian randomization studies.

Funding: NTNU Health, Norwegian University of Science and Technology (grant no. 81771516)