Thursday, August 20, 2015

Is the "Fat Kid" Doomed to Stay Fat Forever? What's the Role of Physical Activity Within a Window of Opportunity?

How large is the impact of not being active on childhood, adolescent and adult obesity. Plus: Are there critical time periods in gestation, infancy childhood and adolescence?
You may have heard the claim that "fat cells form during childhood and puberty and stay forever" before, right? Well, if that's the case it would be logical to assume that our childhood may be a critical developmental windows in which we have the time-limited opportunity to shape or help shape our own or our kids body composition for the rest of our or their lives.

Scientists from Mater Health Services South Brisbane, the University College of London, and the Griffith University have now reviewed the relatively scarce experimental and abundant observational pertinent research in order to examine "the role of physical activity during periods of risk to reduce the probability of obesity onset and maintenance in adulthood" (Street. 2015).
Reduced obese individuals and other things related to "metabolic damage"

Chronic Dieting Can Make You Skinny Fat

Nasty insights into the YoYo-Effect

Is There Diet-Induced Metabolic Damage?

Energy Deficits Can Make Athletes Fat

Fat Cell Size, NAFLD & Reduced Obesity

Metabolic Damage - What's the Evidence?
Unfortunately, but not surprisingly, most of the experimental evidence comes from rodent studies. If we tried to summarize the results of these studies in a half-sentence it would say that they demonstrate general positive effects of early exercise on the outcomes for all animals irrespective of maternal obesity status or post-weaning diet.
"Although high-fat post-weaning diets resulted in generally fatter animals, the body composition, endocrine and immune system profiles of these animals were healthier than non-exercising high-fat diet animals and comparable to standard chow non-exercising animals" (Street. 2015).
Interestingly, these effects do not disappear when the animals stop exercising. Rather than that studies indicate that exercise at an early age can protect animals against obesity onset for 5 weeks following exercise cessation (Caruso. 2013) - that's quite impressive if we take into account that rodents have a much shorter lifespan and a rapid early development period compared to humans (five rodent weeks in the early life are similar to several human years).

In spite of the fact that we don't know for sure for how long these protective effects will last in humans, there's little doubt that the same up-regulation of markers associated with increases in the skeletal muscle mitochondrial function, of which scientists believe that they protect the young rodents from obesity, will occur in humans as well (Shindo. 2014). Luckily, this is not the only thing we already know about rodents and assume for humans. Here's more:
  • Figure 1: If rodents are exercise in "childhood" (3WK), already, they will be significantly leaner - irrespective of whether they are fed an obesogenic HFD or the regular SMD diet (Wagener. 2012).
    the earlier, the better - the earlier young rodents are exercised (e.g. in the rodent equivalent of childhood), the more pronounced the protective effect against adult obesity (Wagener. 2012) - as you can see in Figure 1 earlier exercise will also yield significantly reduced body fat levels on standard rodent chow (SMD - 3WK);
  • muscle & brain are involved - next to changes in the mitochondria, the "stay lean" effect is also mediated by changes in structure and/or function of brain regions involved in appetite regulation in mouse & man (Street. 2015); 
  • males benefit more than females - the benefits of early exercise appear to be more pronounced for male vs. female animals (Schroeder. 2010); whether that's due to the higher muscle mass remains to be elucidated
In view of the fact that corresponding studies in human beings are not just time-consuming and expensive, but could also be unethical (think of kids being randomly assigned to non-exercise groups getting fat and sick as adults), it is not surprising that most of the evidence from human studies is of observational nature. Much in line with the findings from rodent studies, it has been suggested that three critical periods are important for obesity onset before adulthood: gestation and early infancy, the adiposity rebound and adolescence.
"Each period is characterized by substantial yet qualitatively different changes in growth and maturation. The culmination of each period represents a milestone in development and a subsequent reduction in the developmental plasticity of the maturing system. Given the inherently greater plasticity of earlier periods, obesity risk later in the life course is greater if the pre-conditions for obesity are established and maintained early. Disrupting the trajectory of obesity during development is likely to pay dividends in adulthood with a healthier body composition and metabolic profile. The disrupting effect of physical activity is less well understood in relation to obesity risk during and following critical periods" (Street. 2015).
Let's briefly recap what we know about these periods and how exercise during gestation (obviously in this case the mother would exercise), early infancy and adolescence influence our obesity risk as adults:
  • Figure 2: Body fat levels according to quartiles of physical activity in late pregnancy (Harrod. 2014).
    Gestation - Physical activity during pregnancy has been associated with reduced odds of a large-for-gestational age (LGA) infant, as well as reduced risk of small-for-gestational age, which are both linked to increased obesity risks later in life. In addition, there is evidence of reduced body fat levels, but identical lean mass and a significantly reduced risk of macrosomia (=excessive body weight) in babies born to mothers with higher levels of physical activity during pregnancy.

    Overall, however, the existing evidence - specifically for strength training - is conflicting and we are far from fully understanding the complex interactions between physical exercise, nutrition during gestation and the weight and body composition of the newborn baby (a usual more does not necessarily help mor). What appears to be certain though is that if beneficial effects occur, those will last for at least 12-24 months (Mattran. 2011; Chu. 2013). In one study scientists even found significantly reduced obesity risks up to age 5 even if the physical activity of the mother was the only significant difference between the kids (Clapp. 1996)
  • Figure 3: Observational data shows that there is an inverse linear association between infant activity scores and body fat percentages as early as in year 1 (Li. 1995).
    Infancy - Although it is correct that our body composition in infancy is still largely influenced by our mother's physical activity during gestation, there's good evidence that an earlier achievement of gross motor milestones (sitting, crawling, etc.) gives us the activity headstart we need to stay lean. Based on the correlation between earlier motor milestones and lower subscapular and triceps skin-folds measurements of 12 month-old kids Street et al. conclude that  "more active infants depose less fat over the first year [...] because active energy expenditure has resulted in increased metabolic capacity".

    In contrast to rodents, the "early activity bonus" does not last long in humans. With 5 years "early active" children are no longer significantly leaner than their peers, unless they were continuously more active and/or were fed different diets.

    In spite of the fact that early life activity does not provide life-long protection against obesity, though, the experimental and observational evidence of an inverse relationship between physical activity and body fat levels in infancy (Li. 1995) highlights the importance of leading an "active life" - in the most general sense - as early as possible. This is also relevant, because activity builds, while inactivity "kills" muscle, which is in turn associated with a further reduction in physical activity: Overweight infants, for example, have been shown to reach motor milestones later than leaner counterparts (Slining. 2010). Now you've just learned about the link between these milestones and staying lean in a previous paragraph. Accordingly, you will know that this means that the "sweet", chubby babies and toddlers may be caught in a vicious cycle of "obesity > low activity > lower muscle > lower activity > more obesity > lower activity ... "even before the know what the word "activity" means.
    Figure 4: Normal body fat development during infancy (Street. 2015).
    This does not mean that babies have to be "ripped", but I guess we all have seen kids with body fat levels way beyond the normal ~30% at 6 months (see Figure 4). The real problem, however, occurs thereafter, when the slow and steady decline in body fat should be driven by increases in a kid's activity energy expenditure (AEE). The latter takes the role of the energetic needs of growing which have previously been every toddler's #1 energy consumer. If the growth process slows and "activity", which does by the way include "vocalization primarily in the form of crying [which] is the next greatest pre-ambulatory energy cost after the energy cost of growth" (Street. 2015), does not take it's place, obesity ensues.

    Obviously, you could counter that by calorically restricting your toddler, but this is (a) unhealthy and (b) the exact opposite of what the mums and dads do. In fact, way too many of them are priming their kids to become obese sugar addicts by giving their kids a sugar-sweetened beverage (a "healthy baby tea" *rofl*), whenever the kids utter a sound just to make them shut up do. It is thus no wonder that studies have linked infant temperaments that are characterized by negative affectivity/emotionality and a more frequent use of vocal signals such as crying and thus more frequent maternal feeding responses to increased fat gain (Baughcum. 1998; Darlington. 2006). That's alarming, even if it has not yet been conclusively shown that the two are causally and not just corollary related.
  • Does the Optimal Meal Frequency Depend on Age? Study Suggests: Kids Better Eat Often, Adolescents Rather Step Away From Their Sugary Sins - Quality Counts! Read more!
    Childhood - An important feature of childhood development, particularly in terms of its association with increased obesity risk, is a fall in body mass index (BMI) until about 5–7 years of age, which is followed by the so-called "adiposity rebound" (AR).

    The earlier this rebound occurs, i.e. the earlier kids start to become fat again, the higher their risk of obesity as late as adulthood (Whitaker. 1998; Taylor. 2004). More specifically, studies like Whitaker et al. (1998) show that "early gainers" have a 20% higher obesity risk later in life and an extra 20% risk if they were already overweight - or I should say "over-fat" - at the age of 5-7 years.

    It is thus only logical that studies show that obese pre-schoolers often become obese adults (Nader. 2012). Next to the Western junk-food diet, research findings in the recent decades support a relationship between increased obesity risk, low physical activity and high sedentary pursuits during childhood (Reilly. 2010).
    Figure 5: Risk increase / decrease of becoming an obese teenager for weight status at AR, maternal and paternal BMI during; I think it's quite telling that even the "medium" weight (=average kids) already have increased obesity risks, these days (data from Whitaker. 1998).
    A recent study by Schuster et al., for example, shows that "overweight fifth-graders were more likely to become obese if they had an obese parent (P < .001) or watched more television (P = .02)" (Schuster. 2014); and that's only the last in a series of studies suggesting that children who engage in more vigorous physical activity are at reduced risk of obesity, while children who are more sedentary are at a significantly greater risk of becoming obese in adolescence, which happens to be the next and last developmental step we're going to discuss in today's SuppVersity obesity feature.
  • Adolescence - Adolescence is a critical phase in the development of our fat stores. While the years before puberty are characterized by both fat cell hypertrophy (the fat cell size increases), hyperplasia (more fat cells are formed) and apoptosis (fat cells die), most experts agree that the number of apoptotic processes in our adipose tissue declines rapidly as we approach puberty.

    Figure 6: Difference of total fat mass of girls at age 10, 11, 12, 13; all values relative to girls who had a low and maintained a low activity levels (LL) - HH: high activity at baseline, low later, LH: low activity at baseline, high later, HL: high activity at baseline, low later (Völgyi. 2011).
    This decline in the adipose tissue turnover is really bad news and one of the reasons why scientists believe that the "critical window" from the headline of today's SuppVersity article closes during puberty:
    "It is generally thought that alteration in the size of fat cells in adulthood is achievable but maintenance of reduced fat cell size is likely to be difficult because of the mechanisms that may include, e.g. decreased leptin production. Furthermore, while an increase in adipo-cyte number is possible during adulthood, reversal of fat cell number does not occur. Consequently, adolescence represents an additional critical window when physical activity may affect obesity risk (reducing fat cell accretion) in ways it can-not during adulthood (reducing established fat cell number). " (Street. 2015)
    Since adolescence is also associated with an increase in lean mass, including skeletal muscle and bone, it is thus high time to start being, or - better - being even more active. After all, both muscle and bone mass are positively correlated with physical activity levels (Bailey. 1999; Völgyi. 2011).
A 2005 study by D'Andrea et al. shows significant increases in resting energy expenditure after large volume liposuction (all values expressed rel. to baseline). This is the exact opposite of what would happen if the same 4-5% of body fat had been lost by dieting and thus evidence that surgery may help people lose weight without setting them up for the yoyo effect even after the "window of opportunity" closed. 
Liposuction to the rescue! I am usually not a fan of cosmetic surgery, but in view of the fact that D’Andrea et al. (2005) were able to show that large-volume liposuction results in "a significantly improved insulin sensitivity, resting metabolic rate, serum adipocytokines, and inflammatory marker levels" in a clinical study conducted with 123 obese women, it is hard to ignore that the surgery knife may help even if the "Window of Opportunity" has closed, already. The reduction in REE in reduced obese individuals is after all one of the main reasons they regain weight (or struggle with weight regain for the rest of their life). If this problem is in fact triggered by the high amount of emptied fat cells that are left behind after losing more than 40lbs, it's only to assume that the surgical removal of fat cells would not lead to the same "pro-weight gain" problems.
  • If you take a look at the data in Figure 6 it's yet not too late to start being active in puberty. The previously sedentary girls in Völgyi's study (Figure 6 | LH) who started to exercise regularly during puberty, for example,  were similarly lean as their "always active" peers (HH). Probably because they expended more energy, but also because their exercise left them less hungry than their sedentary peers ... that sounds like bogus? Well, take a look at the reduced 24h energy intake Thivel et al. measured in youths who were locked in a metabolic chamber in response to high intensity exercise vs. sitting around (Thivel. 2012 | Figure 7)  - exercise does not make you hungry.
    Figure 7: Much in contrast to what you may expect, obese kids actually eat less, when they are forced to work out. In that, doing high intensity exercise (HIE) is more "satiating" than low intensity (Thivel. 2012).
    Now, if exercise curbs your appetite, while being sedentary increases it and its obesogenic consequences, which in turn reduce your willingness and ability to exercise, it is obvious what Street et al refer to when they are talking about "a two way street" (Street. 2015). It's the previously hinted at vicious cycle in which lower physical activity predisposes to obesity, while obesity in turn predisposes to even greater reductions in physical activity.

    In view of the previously referenced physiological peculiarities, adolescence appears to be the last stage in our development, where increased activity, alone, can go a long and consequential way. It is thus all the more important to break the cycle of being sedentary <> getting fatter before the transition into adulthood takes place. After all, the currently available research leaves little doubt that physical activity during adolescence will promote an adult body composition and metabolic profile that is associated with a reduced obesity risk, and reduced morbidity: Adult women who were more active adolescents, for example, are 50% less likely to be abdominally obese - even if all covariates are controlled for (da Silva. 2015). Physical activity interventions in adults, on the other hand, yield very ambiguous results. In most cases, however, being more active alone will not make a significant enough difference to trigger fat loss and instigate health improvements. 
Shi et al. conducted an interesting experiment that highlight the role of low leptin in weight regain. They fattened rodents up, dieted them down and found that the weight reduced rodents whose weight loss had stagnated after 3 weeks had the same low leptin levels as the normal-weight significantly leaner rodents. The hypothesis is that this is due to having more, but empty fat cells that produce way too little leptin for the total amount of body fat, because the amount of leptin that's produced depends in a non-linear way on the level of fat in the cells. Rodent bogus? Well several human studies showing a reversal of neurological, endocrine and metabolic abnormalities in reduced obese indiv. with leptin (Rosenbaum. 1997, 2005 & 2008) suggest that this may actually be happening in man & woman, too.
So what? With the vicious cycle of being sedentary, getting fat, being even more sedentary and getting even fatter, we are back to our original question which was whether you'd have to stay fat forever if you end up being fat at the end of puberty. I wouldn't go so far as to say that your fate is determined, but it's hard to ignore the evidence that our kids can at least avoid adding additional fat cells and thus increase their chance of life-long leanness by leading an active lifestyle. We, on the other hand are in a very compromised situation. In contrast to studies in adolescents, many studies in adults show that even combined aerobic and resistance training, may effectively shed our love-handles once we are adults (Willis. 2012).

Dieting, on the other hand, may successfully reduce our body weight, but the risk of "refilling" the fat cells we've created as babies, children and adolescents, when the body fat turnover and the natural "apoptotic death" of fat cells stagnates, increases with every pound of extra body fat we've "acquired" as babies, children and teens. Why exactly this is the case has not been fully elucidated, yet. I personally find that Shi's 2009 hypothesis that says (generally speaking) that the high number of small fat cells in people who have gained a lot of fat before adulthood are left with after a diet won't produce enough leptin to signal the body that they've achieved a new steady state. Constant hunger and rapid and easy fat gain even from consuming the "exact" amount of energy they should need are the nasty consequences some of you may have experienced first-hand | Comment!
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