REGULATION OF PHYSICAL ACTIVITY

An in-depth review of factors and mechanisms that regulate daily physical activity is beyond the scope of this literature review, due to the number of possible factors and their inter-relatedness. Regulation of physical activity can be divided simply into biological/genetic factors, environmental factors, or their interactions. This approach is common in genetic studies (Knab and Lightfoot, 2010). From a more behavioral perspective, Dishman et al. (1985) divided factors that affect physical

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Figure 5. Regulation of physical activity via skeletal muscle contraction. Classification of the regulation factors according to Bauman et al. (2012).

activity in to three categories; 1) personal characteristics, 2) environmental charactersitics, and 3) activity characteristics. This model can be further refined into an ecological model, in which factors that can contibute to physical activity have been divided into five categories; 1) individual, 2) interpersonal, 3) environmental, 4) regional or national policy, and 5) global factors (Bauman et al., 2012). Furthermore, the individual category can be diveded into interplay of psychological and biological factors, which include evolutionary physiology and genetic factors (Figure 5).

Twin and family studies have reported that heritability explains 0–85% of physical activity (de Vilhena e Santos et al., 2012). This large variability between the studies is most likely explained by the difference in the physical activity measurement methods, design of the study, population investigated, and the phenotype studied (determinant of physical activity). Among 13–16 year old children, it has been shown that mostly environmental factors contribute to the participation in sports (Stubbe et al., 2005). The influence of genetic factors however increases with age, explaining 35% of the variance in sports participation among 17–18 year olds and 85% among 19–20 year old subjects (Stubbe et al., 2005). From 18–29 year olds to 50–59 year olds, the effect of heritability seems to steadily decrease from 64% to 32%, respectively, until it curves back to 62%

among subjects who were at least 60 years old (Kaprio et al., 1981). These findings together with findings from a 26-week follow-up study on mice (Turner et al., 2005) suggest a possible gene x age interaction effect on physical activity.

Several possible candidate genes and quantitative trait loci for physical activity have been identified and previously reviewed (Dishman, 2008; Lightfoot, 2011a;

Lightfoot, 2011b; de Vilhena e Santos et al., 2012; Bauman et al., 2012). The current evidence about the candidate genes is inconsistent, possibly due to the variability in the studied phenotype. In addition, the specific mechanism by which physical activity genes mediate their regulative effect is unknown. In the only genome-wide association study (GWAs) on regular leisure-time exercise (≥4 METh per week) 37 novel single nucleotide polymorphisms (SNPs) from 3 different DNA regions were found, including 3'-phosphoadenosine

5'-Individual

Regulators of physical activity

Skeletal muscle force production PHYSICAL ACTIVITY

Inter-personal Environmental Regional or

national policy Global

phosphosulfate synthase 2 (PAPSS2) gene (De Moor et al., 2009). PAPSS2 has loosely been associated with the ability to exercise, which could influence physical activity (Ikeda et al., 2001; Rico-Sanz et al., 2004). Regulation of exercise ability has also been associated with the nescient helix-loop-helix 2 (NHLH2) gene and solute carrier family 2 facilitated glucose transporter, member 4 (SLC2A4) gene (Tsao et al., 2001; Good et al., 2008). SLC2A4, which codes primary glucose transporter (GLUT4) of skeletal muscles, could increase the tolerance for exercise-induced fatigue. Meanwhile Good et al. (2008) have suggested that NHLH2 could affect peripherally by regulating skeletal or heart muscle function. It has also been proposed that the hypothalamic expression of NHLH2 transcription factor could decrease energy expenditure by decreasing the level of functional hypothalamic neuropeptides (Jing et al., 2004). In addition, inhibition of NHLH2 activity in brain could inhibit β-endorphin response to exercise, thus reducing the motivation to exercise (Good et al., 2008). NHLH2 has also been associated with the regulation of melanocortin 4 receptor (MC4R) gene and melanocortin pathway (Wankhade and Good, 2011). MC4R is another candidate gene for physical activity and it has been shown to regulate the physical activity response to altered diet (Butler et al., 2001; Loos et al., 2005; Cole et al., 2010). Furthermore, dopamine receptor genes (DRD1, DRD2, DRD4) may also regulate physical activity through the dopamine system, which is involved in the regulation of motor movement, reward, and motivation (Knab and Lightfoot, 2010). In fact, it has been postulated that the dopamine system could increase the inner drive for voluntary physical activity (Knab and Lightfoot, 2010; Lightfoot, 2011a). In contrast, Jozkow et al.

(2013) have reported no association between the DRD2 or DRD4 single nucleotide polyphormisms (SNPs) and physical activity in healthy men. To support the role of the dopamine system in the regulation of self-reported physical activity, Teske et al. (2008) have reported that dopaminergic pathways interact reciprocally with several different neuropeptides that have been linked to physical activity, including orexin. The multifactorial role of neuropeptides, especially orexin, in the regulation of physical activity has previously been extensively reviewed (Teske et al., 2008; Kotz et al., 2012; Butterick et al., 2013).

Early development, prenatal environment, epigenetic inheritance, early-life nutrition or physical activity status, and behavioral development can also influence physical activity later in life. In rodents, fetal growth restriction (Baker et al., 2010), maternal undernourishment (Vickers et al., 2003), and protein intake restriction (Bellinger et al., 2006) during pregnancy have been associated with physical inactivity. In humans, both low and high birth weight has been associated with decreased odds of participation to LTPA (Andersen et al., 2009).

In contrast, birth weight has not been linked to reported sedentary lifestyle in 10–

12 year old children (Hallal et al., 2006; Mattocks et al., 2008). Objectively measured physical activity (accelerometer) has however been greater among 11–

12-year old children whose mothers did not smoke and were physically more active during pregancy (Mattocks et al., 2008). The molecular mechanisms underlying the possible association between the prenatal environment and

physical activity are not understood, albeit epigenetics including DNA methylation or histone acetylation are likely to have an affect.

In addition to genes, there are multiple individual, interpersonal, and environmental factors that can modify physical activity (Dishman et al., 1985).

The leading environmental barrier for exercise is the concern about the safety of the neighborhood (Mier et al., 2007; Kamphuis et al., 2008; Caperchione et al., 2009) but also lack of facilities (Brownson et al., 2001; Mier et al., 2007; Skowron et al., 2008), and poor weather (Hays and Clark, 1999; Mier et al., 2007), have been reported. Barriers related to the household are the lack of childcare, insufficient space at home (Piana et al., 2013), financial issues (Caperchione et al., 2009), and social deprivation (Kamphuis et al., 2008). As expected, the largest group of possible barriers are related to individual factors, including lack of time (Brownson et al., 2001; Mier et al., 2007), lack of motivation (Hays and Clark, 1999; Brownson et al., 2001), negative outcome expectancies, low self-efficacy (Kamphuis et al., 2008), health issues (Hays and Clark, 1999; Mier et al., 2007;

Caperchione et al., 2009), daytime sleepiness (Chasens et al., 2009), obtaining enough occupational activity (Brownson et al., 2001), religious activities (Caperchione et al., 2009), and fatigue (Brownson et al., 2001; Piana et al., 2013).

It has also been suggested that the fear of losing the security of habitual behavior can feed the resistance to change among obese people (Piana et al., 2013).

Interpersonal factors that may affect physical activity include limited social connections and support (Kamphuis et al., 2008; Caperchione et al., 2009), language (Caperchione et al., 2009), and cultural norms or codes (Caperchione et al., 2009). It is worth noting that the relevance of these modulators of physical activity or “barriers to exercise” tends to vary depending on the sex, race, socioeconomic position, and cultural background (Bauman et al., 2012). Based on the 574 double labeled water measurements, the physical activity related energy expenditure was 11% lower among women compared to the age and size matched men (Black et al., 1996). This difference could be intermediated by difference in the sex hormones, although the evidence is limited (Bowen et al., 2011).