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Physical Activity, Fitness, Glucose Homeostasis, and Brain Morphology in Twins

Purpose: The main aim of the present study (FITFATTWIN) was to investigate how physical activity level is associated with body composition, glucose homeostasis, and brain morphology in young adult male monozygotic twin pairs discordant for physical activity.

Methods: From a population-based twin cohort, we systematically selected 10 young adult male monozygotic twin pairs (age range, 32–36 yr) discordant for leisure time physical activity during the past 3 yr. On the basis of interviews, we calculated a mean sum index for leisure time and commuting activity during the past 3 yr (3-yr LTMET index expressed as MET-hours per day). We conducted extensive measurements on body composition (including fat percentage measured by dual-energy x-ray absorptiometry), glucose homeostasis including homeostatic model assessment index and insulin sensitivity index (Matsuda index, calculated from glucose and insulin values from an oral glucose tolerance test), and whole brain magnetic resonance imaging for regional volumetric analyses.

Results: According to pairwise analysis, the active twins had lower body fat percentage (P = 0.029) and homeostatic model assessment index (P = 0.031) and higher Matsuda index (P = 0.021) compared with their inactive co-twins. Striatal and prefrontal cortex (subgyral and inferior frontal gyrus) brain gray matter volumes were larger in the nondominant hemisphere in active twins compared with those in inactive co-twins, with a statistical threshold of P < 0.001.

Conclusions: Among healthy adult male twins in their mid-30s, a greater level of physical activity is associated with improved glucose homeostasis and modulation of striatum and prefrontal cortex gray matter volume, independent of genetic background. The findings may contribute to later reduced risk of type 2 diabetes and mobility limitations.

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Alex’s Notes: Physical activity is a hot-topic here at Super Human Radio, and not without good reason. For instance, being more physically active has been associated with a beneficial metabolic phenotype that results in enhanced fat oxidation, reduced protein degradation, and greater fat loss when dieting. Perhaps more illustrating are the effects of not being physically active, which results in twice as many deaths as obesity, a greater number of metabolic risk factors, and the creation of a devastating feed-forward loop with frailty.

Despite the importance of being active, two-thirds of US adults sit for at least seven waking hours per day and engage in no moderate-intensity exercise. Perhaps this is owed to them being overweight or obese, which has been implicated in limiting physical ability. Or perhaps their environment is not appealing. Whatever the reason, it is a habit that must be broken. Health benefits are seen with as little as 30 minutes of brisk walking three days per week, but increased mental health and sleep quality require more vigorous activities, and the frequency of being physically active may be more important than the volume of activity. Fitness apps, dog walking, and active friends are all ways to encourage more activity.

With all that said, many of the chronic diseases that exercise is seen as protective against have a long presymptomatic phase that can sit dormant for decades before any noticeable disease signs show up. Studies assessing the effects of physical (in)activity thus require very long follow-up durations, which can be challenging and impractical in many settings. Moreover, observational studies don’t allow for causal inferences. Both genetics and the environment can influence how physical (in)activity affects an individual. To help overcome these barriers, Rottensteiner et al. decided to investigate the effects of physical activity in monozygotic twin pairs, which controls for genetic differences and also largely for environmental differences as they are typically raised in the same household as children.

The study sample included ten twin pairs that were considered discordant with their physical activity. Physical activity questionnaires, fitness testing, body composition, and blood-borne measurements were all performed and/or collected on two simultaneous days. Questionnaires revealed that physical activity was similar until three years preceding the study, which was when the twins were about 30 years old. During this time, the “active” twin engaged in ≥1.5 MET hours per day of leisure time physical activity and had greater involvement in more vigorous sports. Additionally, the “inactive” twin had ≤5 MET hours per day of total leisure-time physical activity.

Ultimately what it boiled down to was an active twin who engaged in about three hours more per day of leisurely physical activity, with the most common being walking and jogging. And “leisurely” really does define the intensity, as the difference in leg extension strength and VO2 max were minor between the twins.

So what did the extra activity bestow aside from fitness?

For starters, the active twins had a greater amount of lean body mass (+1.4 kg) and much less fat mass (-3.3 kg) leading to a body fat percentage of 20.7% vs 24%. They also had a lower waist circumference and greater insulin sensitivity. But these outcomes are to be expected. Far more interesting was the fact that the active twin had larger grey matter volume in several regions of the brain implicated in the metabolic syndrome, motor control, language, memory, and emotion.

So what are we left with? Well, this study was able to control for genetic differences and many environmental influences, and thus help single out physical activity as the only variable. And while there is no doubt to be confounding variables hidden somewhere, this study provides strong evidence that leisure-time physical activity leads to increased fitness, a more favorable body composition, improved glucose tolerance, and favorable changes in brain morphology.


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