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!

References:

• Bailey, D. A., et al. "A six‐year longitudinal study of the relationship of physical activity to bone mineral accrual in growing children: the University of Saskatchewan Bone Mineral Accrual Study." Journal of Bone and Mineral Research 14.10 (1999): 1672-1679.
• Baughcum, Amy E., et al. "Maternal feeding practices and childhood obesity: a focus group study of low-income mothers." Archives of Pediatrics & Adolescent Medicine 152.10 (1998): 1010-1014.
• Caruso, V., H. Bahari, and M. J. Morris. "The Beneficial Effects of Early Short‐Term Exercise in the Offspring of Obese Mothers are Accompanied by Alterations in the Hypothalamic Gene Expression of Appetite Regulators and FTO (Fat Mass and Obesity Associated) Gene." Journal of neuroendocrinology 25.8 (2013): 742-752.
• Chu, Lisa, et al. "Impact of maternal physical activity and infant feeding practices on infant weight gain and adiposity." International journal of endocrinology 2012 (2012).
• Clapp, James F. "Morphometric and neurodevelopmental outcome at age five years of the offspring of women who continued to exercise regularly throughout pregnancy." The Journal of pediatrics 129.6 (1996): 856-863.
• D’Andrea, Francesco, et al. "Changing the metabolic profile by large-volume liposuction: a clinical study conducted with 123 obese women." Aesthetic plastic surgery 29.6 (2005): 472-478.
• da Silva Garcez, Anderson, et al. "Physical Activity in Adolescence and Abdominal Obesity in Adulthood: A Case-Control Study Among Women Shift Workers." Women & health ahead-of-print (2015): 1-13.
• Darlington, Anne-Sophie E., and Charlotte M. Wright. "The influence of temperament on weight gain in early infancy." Journal of Developmental & Behavioral Pediatrics 27.4 (2006): 329-335.
• Harrod, Curtis S., et al. "Physical activity in pregnancy and neonatal body composition: the healthy start study." Obstetrics & Gynecology 124.2, PART 1 (2014): 257-264.
• Li, Ruowei, et al. "Relation of activity levels to body fat in infants 6 to 12 months of age." The Journal of pediatrics 126.3 (1995): 353-357.
• Mattran, Kelly, et al. "Leisure-time physical activity during pregnancy and offspring size at 18 to 24 months." Journal of Physical Activity and Health 8.5 (2011): 655.
• Nader, Philip R., et al. "Next steps in obesity prevention: altering early life systems to support healthy parents, infants, and toddlers." Childhood Obesity (Formerly Obesity and Weight Management) 8.3 (2012): 195-204.
• Reilly, John J. "Low levels of objectively measured physical activity in preschoolers in child care." Medicine and science in sports and exercise 42.3 (2010): 502-507.
• Rosenbaum, Michael, et al. "Effects of Weight Change on Plasma Leptin Concentrations and Energy Expenditure 1." The Journal of Clinical Endocrinology & Metabolism 82.11 (1997): 3647-3654.
• Rosenbaum, Michael, et al. "Low-dose leptin reverses skeletal muscle, autonomic, and neuroendocrine adaptations to maintenance of reduced weight." Journal of Clinical Investigation 115.12 (2005): 3579.
• Rosenbaum, Michael, et al. "Leptin reverses weight loss–induced changes in regional neural activity responses to visual food stimuli." The Journal of clinical investigation 118.7 (2008): 2583.
• Schroeder, Mariana, et al. "Post-weaning voluntary exercise exerts long-term moderation of adiposity in males but not in females in an animal model of early-onset obesity." Hormones and behavior 57.4 (2010): 496-505.
• Schuster, Mark A., et al. "Changes in obesity between fifth and tenth grades: A longitudinal study in three metropolitan areas." Pediatrics 134.6 (2014): 1051-1058.
• Shi, Haifei, et al. "Diet‐induced Obese Mice Are Leptin Insufficient After Weight Reduction." Obesity 17.9 (2009): 1702-1709.
• Shindo, Daisuke, Tomokazu Matsuura, and Masato Suzuki. "Effects of prepubertal-onset exercise on body weight changes up to middle age in rats." Journal of Applied Physiology 116.6 (2014): 674-682.
• Slining, Meghan, et al. "Infant overweight is associated with delayed motor development." The Journal of pediatrics 157.1 (2010): 20-25.
• Street, S. J., J. C. K. Wells, and A. P. Hills. "Windows of opportunity for physical activity in the prevention of obesity." Obesity Reviews (2015).
• Taylor, Rachael W., et al. "Rate of fat gain is faster in girls undergoing early adiposity rebound." Obesity research 12.8 (2004): 1228-1230.
• Thivel, David, et al. "The 24-h energy intake of obese adolescents is spontaneously reduced after intensive exercise: a randomized controlled trial in calorimetric chambers." PloS one 7.1 (2012): e29840.
• Wagener, A., A. O. Schmitt, and G. A. Brockmann. "Early and late onset of voluntary exercise have differential effects on the metabolic syndrome in an obese mouse model." Experimental and Clinical Endocrinology and Diabetes 120.10 (2012): 591.
• Whitaker, Robert C., et al. "Early adiposity rebound and the risk of adult obesity." Pediatrics 101.3 (1998): e5-e5.

Organ Specific Resting Metabolic Rates and Diet-Induced "Metabolic Damage". Plus: At Rest Heart, Liver & Kidney Consume 83x More Energy/kg Organ Mass Than Muscle

No, your muscles are not the primary gas guzzler in your body.

The problems arising as a consequence of a diet-induced reduction of the metabolic rate are among the recurring themes here at the SuppVersity. For a good reason, as I would say. After all, they are the #1 reason for weight loss plateaus and the yoyo effect. Although the notion that "calories count" is not very popular these days there is no debating that an energy deficit is a necessary prerequisite for weight loss. The problem however is that you cannot determine your energy balance with a calculator, a body fat caliper and a scale. There are way too many other factors involved - the amount, macro- and micronutrient composition, timing, frequency, volume, texture and palatability of the ood you eat, stress, hormonal factors, etc - all of which will affect the amount of energy you expend and subvert the results of over-simplistic calories-in vs. calories-out calculations.

What are the most notorious gas guzzlers in our body?

Things would actually already be complex enough, if we focused solely on that "input" <> "output" recursion, but unfortunately, even the notion of a "global" (=valid for the whole body) metabolic rate is nothing we can really rely on. If we wanted to have a somewhat more accurate estimate of our basal energy requirements, i.e. the amount of energy we need if we don't move all day (which is basically what the average Westerner does, these days ;-), we would have to know the individual energy requirements of all our major organs and add them up, using a formula like this:

The more you eat, the more you burn. You can find more evidence that men & women are no bomb-calorimeters here

240x brain mass in kg

+ 440x heart mass in kg
+ 200x liver mass in kg
+ 440x kidney mass in kg

+ 13x skeletal muscle mass in kg
+ 4.5x adipose tissue mass in kg

+ 12x residual mass in kg

This formula, which was developed based on studies of Elia et al. in 1998, assumes that the metabolic activity of an organ increases linearly with its mass and that the specific metabolic rates (ki-values, i.e. 240 for the brain, 440 for the heart, etc.) are accurate. In the average, normal weight non-dieting individual these values are constant and have been confirmed lately in a set of experiments that were conducted by Wang et al. (see figure 1)

Figure 1: ki-Values of adipose tissue, skeletal muscle, liver, brain, heart, kidneys, residual volume from the Wang studies; all values expressed relative to the reference values from Elia (1998)

These studies, which were published subsequently in 2010, 2011 and 2012, also reported that there are distinct trends for decreasing ki-values and thus lower resting energy expenditures at identical organ masses in both obese / lean and older / younger individuals - an effect which can be explained by either lower cellularity or lower specific metabolic rates of the respective organs and tissues. In light of the fact that the "organ weight x ki-value"-calculations are very accurate and that

"there is only a small and nonsignificant difference between REEm [measured resting energy experience] and REEc [the energy experience calculated based on ki-values and organ masses] of about 13 to 80 kcal/day" (Müller. 2013b)

it should be obvious that both aging and already being obese put you at a higher risk of weight gain in a society where energy dense foods and large portion sizes are the rule, not the exception.

Is there something like organ specific metabolic damage?

A couple of recent studies have investigated the effects of weight loss and regain on organ-specific energy expenditure in order to find out if this may be the, or at least one of the underlying reason for the reduced resting energy expenditure in formerly obese individuals (Müller. 2013a; Bosy-Westphal. 2009 & 2013). These studies support the idea of a fall in the organ size and weight and the corresponding ki-values of high metabolic rate organs (heart, kidney, liver) with weight loss. Bosy-Westphal (2009), for example report a -136kcal/day reduction in resting energy expenditure (REEm = measured) with 4-6% loss of liver, heart and kidney mass in obese women after 9.5kg body weight loss (2.6% fat free mass).

Figure 2: Difference between measured and calculated energy expenditure in MJ/day at baseline, after weight loss and regain in  47 obese men and women who lost 12kg (weight stable) and 9kg (weight regainers) in a study by Bosy-Westphal et al. from 2013

"In addition, the effect of weight loss and weight regain over a longer follow-up period of 6 months had been studied in 47 obese males and females (Bosy-Westphal. 2013). There were considerable differences between weight-reduced/weight-stable individuals compared with weight regainers. Over a period of 6 months, weight-reduced/weight-stable individuals had lost 12 kg body weight, the weight change-associated changes in the REEm - REEc values were 33 and 45 kcal/day, with initial weight loss and with long-term follow-up (i.e. between 12 weeks and 6 months). By contrast, weight regainers regained 6.3 kg body weight after an initial loss of about 9 kg. The corresponding data on the weight changeassociated changes in the REEm - REEc values were 69 and 10 kcal/day, respectively. Individual data for the group ‘regainers’ at basal before and after weight loss, as well after weight regain, are shown in [figure 2]. The changes in the REEm- REEc values argue for changes in specific metabolic rates with weight changes." (Müller. 2013b)

What? Ok, I have to admit that this paragraph from Müller's 2013 review of the literature is not actually easy to understand. So let's take a look at the data in figure 2 again. The main message here is that the weight loss narrows the natural spectrum of REEs down to the minimal requirements of your organs. In other words, the body is running on low fumes and is thus particularly prone to weight regain which can - but does not have to - lead to an increase in the per pound organ weight energy expenditure that would then become obvious in the form of a larger difference between the measured (REEm) and calculated (REEc) resting energy expenditure (green and red circles in figure 2). With the pre-post weight regain difference being 69 vs. 10, it is yet unfortunately more common that the initial organ energy expenditure is not being restored (red circle in figure 2) and the energy expenditure remains low although people regain a lot if not all of their weight.

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Suggested read: "Do Chronic Energy Deficits Make Athletes Fat? The Longer & More Severe You Starve, the Fatter You Are. Irrespective of What the Calories-in-VS-Calories-Out Formula May Say" | read more

What can you do with this information? Not that much, I have to admit. If anything the major contribution of non-muscle tissue to the diet induced reduction of the resting metabolic rate should remind you that it may be at least equally important to spare the mass of the organs in your splachnic bed as it is to maintain as much lean muscle tissue as possible when your dieting.

I don't know if you remember the recent study about citrulline and it's effect on the maintenance of muscle and visceral tissue mass (see figure 1 in the respective article) or previous SuppVersity posts on other non-essential amino acids, such as glutamine or arginine? All of them are primarily "organ food" and an adequate provision of these conditionally essential amino acids should be considered as important as the provision of the purportedly muscle-protecting BCAAs if you want to keep the loss of organ mass at a minimum and your resting metabolic rate up. Whether and how you can influence the individual metabolic rate, of these organs is yet a totally different question to which no one has found a definitive answer, yet.

References:

• Bosy-Westphal A, Kossel E, Goele K,et al. Contribution of individual organ mass loss to weight-loss associated decline in resting energy expenditure. Am J Clin Nutr 2009; 90:993–1001.
• Bosy-Westphal A, Schautz B, Lagerpusch M,et al.Effect of weight loss and regain on adipose tissue distribution, composition of lean mass and resting energy expenditure in young overweight and obese adults. Int J Obes 2013.
• Elia M. Organ and tissue contribution to metabolic rate. In: Kinney J, Tucker HN, editors. Energy metabolism: tissue determinants and cellular corollaries. New York: Raven Press; 1992. pp. 61–79
• Müller MJ, Bosy-Westphal A. Adaptive thermogenesis with weight loss in humans. Obesity 2013a; 21:218–228.
• Müller MJ, Wang Z, Heymsfield SB, Schautz B, Bosy-Westphal A. Advances in the understanding of specific metabolic rates of major organs and tissues in humans. Curr Opin Clin Nutr Metab Care. 2013b Sep;16(5):501-8.
• Wang Z, Ying Z, Bosy-Westphal A,et al.Specific metabolic rates of major organs and tissues across adulthood: evaluation by mechanistic model of resting energy expenditure. Am J Clin Nutr 2010; 92:1369–1377.
• Wang Z, Ying Z, Bosy-Westphal A,et al.Evaluation of specific metabolic rates of major organs and tissues: comparison between men and women. Am J Hum Biol 2011; 23:333–338.
• Wang Z, Ying Z, Bosy-Westphal A,et al.Evaluation of specific metabolic rates of major organs and tissues: comparison between nonobese and obese women. Obesity 2012; 20:95–100.

Get Lean & Stay Lean with Emedin, Galangin & Antibiotics. Plus: Breakfast & Morning Glucose Metabolism. Diet Once, Never Eat to Satiety Again? Adipocyte Size & NAFLD

Instead of making excuses for posting yet another "short news" collection instead of the next installment of the Athlete's Triad series, I will honestly tell you that I simply wasn't in the mood. Moreover, I have the feeling that I have already outlined what is going to work, i.e. train less, eat more and don't get all psyched up about being lean and looking good. Live your life! Against that background my gut tells me that any further details would just get you off track and back into the viscous cycle of overtraining, overdieting and overthinking why things don't work out for you by evoking the impression that as long as you take supplement X you could get away with doing a little bit 'less less' and eat a little bit 'less more'.

This would be about as counter-productive as the eternal quest for the ultimate body fat blocker or fat burner of which today's Get lean and Stay Lean Quickie does actually feature three. While the temporary use of all of them as a crutch or 'afterburner' to a reasonably planned diet and workout regimen certainly makes sense, it's not like anyone of us got fat, because he or she was "fat burner deficient". A fat burner is not an essential nutrient and only an adjunct to diet and exercise! Keep that in mind not just when you read the following short news items, but also whenever you enter a supplement store (real or on the Internet) and find a new "revolutionary fat burner" on sale -- regardless of whether it has Dr. Oz or Mr. O on the packaging it won't actively, i.e. on its own and in the absence of a dialed in nutritional regimen, make you lose body fat.

• Cassia tora (Leguminosae) seed, yet another "next big thing" to get rid of the blubber?  (Tzeng. 2012 --) The results the scientists from the Department of Internal Medicine, at the Pao Chien Hospital in  Ping Tung City will be publishing in the January 2013 issue of Food Chemistry do at at least look intriguing.  Although - and this goes to show you that SuppVersity readers always (well "almost always" ;-) are the first know first - at least one of the active ingredients in Cassia tora, which is also known as Senna tora and is, besides its use in Ayurveda medicine, also used in Sri Lankan cousin, is an old friend: Emodin! The stuff that gives rhubarb the fat burning prowess you read about in not  too long ago, here at the Suppversity.
  
  

  

  CSEE  had dose dependent ameliorative effects on body weight gain and visceral body fat levels that were - ad the highest dose - identical to those of the thiazolidinedione (TZD) drug pioglitazone (Tzeng. 2012)

  After fattening them for 2 weeks with the notorious high fat diet, the Koreans assigned their now obese lab rats to groups who received either
  
  • Cassia seed ethanol extract (CSEE) by oral gavage, once per day for 8 week with CSEE doses of 100, 200, and 300 mg/kg in a volume of 2 ml/kg distilled water,
  • the diabetes drug pioglitazone dosed at 20mg/kg/day, or
  • a placebo, containing just the distilled water.
  Without any effects on the amount of food the animals consumed, the Cassia seed ethanol extract totally blunted the HFD induced weight gain (weight gain was identical to control group on normal chow, see figure to the right).
  
  In that. the highest dosage had the greatest effect on both body weight gain, as well as plasma lipid levels and epididymal WAT sizes in HFD-fed rats. These effects were probably mediated by CSEE's beneficial effect on the phosphorylation of AMP-activated protein kinase (AMPK) and its primary downstream targeting enzyme, acetyl-CoA carboxylase. In addition, the researchers found that the cassia seed extract directly increased genes that are responsible for fatty acid oxidation and down-regulated their fat synthesizing counterparts in the visceral white adipose tissue of the animals.
  
  Whether CSEE is going to be a go-to supplement of the future cannot be said, now. What is certain, however, is that it constitutes yet another example of a potentially highly effective natural alternative to the established pharmacological 'treatment' (or rather management) of the diabesity epidemic.
  
• Obese, once and forever, unless you diet for the rest of your life? (Kirchner. 2012) -- A paper that's been published in the latest issue of the Journal of the American Diabetes Association, clearly suggests that the ravenous appetite of "reduced-obese" individuals, i.e. people who have been dieting for weeks and months to shed they weight they have accumulated over years is not (solely) psychologically induced gluttony.
  
  

  

  Suggested read: "Longterm 5% Calorie Restriction & Longterm Dieting Make You Fat and Insulin Resistant." (read full article)

  When Kirchner et al. put their diet-induced obese mice were on a  food restricted for 5 weeks, they did in fact reach the same body fat levels as age-matched rodents who had never received anything but the standard chow. Their  blood glucose levels normalized and their insulin sensitivity increased, but the "reduced-obese" mice also showed markedly increased fasting-induced hyperphagia. In fact, when they given ad libitum access to their beloved high fat diet, they ate like there was no tomorrow and ended up gaining weight at a much faster pace than their never-obese peers, who were likewise allowed free access to the HFD.
  
  And it gets even worse, as the conclusion the scientists draw based on their results says that despite the fact that "caloric restriction on a HFD provides metabolic benefits", it may actually require a previously obese dieter to continue on the path of caloric restriction (i.e. never eat to 'satiety') for the rest of his/her life!
  
• Morning to evening decline in insulin response to carbs suggests breakfast is the time where your body reacts most sensitive to carbs (Saad. 2012) -- Likewise published in the latest issue of Diabetes is a study by Ahmed Saad and colleagues from the Mayo College of Medicine in Rochester and the the University of Padova in Italy, which does at first not really sound like it was revolutionary new. Two definitive advantages of the study at hand were yet that the scientists used healthy individuals as subject and gave them regular mixed meals instead of a glucose solution in order to confirm the existence and identify the characteristic features of the diurnal pattern of glucose tolerance most people take for granted.
  
  

  

  The implications of this study for intermittent fasting are not as clear as you may think and certainly don't imply that you must break your fast in the morning (read more about breaking the fast, here)

  Overall 20 healthy volunteers with normal fasting glucose (4.8 ± 0.1 mmol/L) and HbA_1c (5.2 ± 0.0%) participated in the study. They were provided with identical mixed meals during breakfast, lunch, or dinner at 0700, 1300, and 1900 h in a random order on 3 consecutive days. Physical activity was held constant so that e.g. muscle glycogen depletion and subsequent increases in AMPK induced GLUT-4 expression  would not skew the results.
  
  What Saad et al. fonud was that the postprandial glucose excursion was significantly lower (P < 0.01) at breakfast than lunch and dinner. At the same time the β-Cell responsivity to glucose was higher. This means there was more insulin released per unit of glucose, than during lunch or dinner.
  
  The time the hepatic insulin extraction was also lower at breakfast; although the difference reached statistical significance only in comparison to the dinner condition. Since the overall meal glucose appearance did not differ between meals and that the suppression of endogenous glucose production "tended to be lower (P < 0.01) and insulin sensitivity tended to be higher (P < 0.01) at breakfast than at lunch or dinner" (Saad. 2012), it is no wonder that the spike in blood glucose was largely augmented, when the subjects consumed the standardized meal for breakfast.
  
• Adipocyte size is a determinant of non-alcoholic fatty liver disease (NAFLD) risk (Petäjä. 2012) -- One thing scientists still have not really understood is how some obese people seem to be way better off than others, although their BMIs, fat and lean mass appears to be identical. In view of the latest paper by a group of researchers from Finland and Sweden on the association between the average fat cell size and the occurrence of NAFLD, it could well be that ratio of the total adipose volume to the total fat cell number, which obviously is the adipocyte size, may be providing at least another piece to the puzzle that holds the answer to this question.
  
  

  

  In a previos post on the yoyo effect, I already discussed some aspects of adipocyte morphology - read more

  The scientists have studied 119 non-diabetic subjects in a cross-sectional study. The participants had a median age of 39 (26-53) years, and a mean BMI of 30.0±5.7kg/m². Subcutaneous abdominal fat cell size, as well as the total amount of liver fat were measured by proton magnetic resonance spectroscopy, intra-abdominal (IA) and abdominal subcutaneous adipose tissue (SC) volumes by magnetic resonance imaging (MRI) and an additional gene analysis yielded information about the genotype (susceptible or not susceptble to metabolic syndrome) of the individuals.
  
  Simply based on a multiple linear regression analysis, age, gender, BMI, the intra-abdominal to subcutaneous fat ratio and the subject's PNPLA3 genotype, the results were only able to explain 42% of the variation of the liver fat. The inclusion of the adipocyte sizes increased the predictive value by 11%, so that "21% of the known variation in liver fat could be explained by adipocyte size alone" (Petäjä. 2012) This does yet also mean that once we are up to a 90% explanation  (which is unrealistic, by the way) the adipocyte size will only be able to explain "of the known variations".
  
• Antibiotic that's commonly used in animal fattening kills body fat (Szkudlarek-Mikho, 2012) -- Reserachers from the College of Medicine at the University of Toledo in Ohio have found that polyether ionophoric antibiotics including monensin, salinomycin, and narasin, which are widely used in veterinary medicine and as food additives and growth promoters in animal husbandry including poultry farming have toxic effects on adipose cells.
  
  

  

  Whether eating the chicken that ate antibiotics is going to make  you lean does still have to be established. Based on the results of the study at hand, it does however appear likely that eating antibiotics could - I do however doubt that they will achieve that without potentially serious side effects.

  Although previous studies suggest that salinomycin has anti-carcinogenic effects (Huczyński. 2012), the sharp increase in poultry consumption over the last decade(s) and the increased use of these "growth promoting" antibiotics by veterinaries and poultry farmers has often been suspected to be involved in the increase in metabolic and autoimmune diseases.
  
  At least in view of the former, i.e. metabolic diseases in general and obesity, in particular, it may therefore be surprising that the scientists from the University of Toledo discovered that the tested ionophoric antibiotics did not just inhibit the differentiation of cancer, but also that of preadipocytes into adipocytes:
  

  "The block of differentiation is not due to the induction of apoptosis nor the inhibition of cell proliferation. In addition, salinomycin also suppresses the transcriptional activity of the CCAAT/enhancer binding proteins and the peroxisome proliferator-activated receptor γ." (Szkudlarek-Mikho. 2012)

  Now, I would fully subscribe to the scientists suggestion that these "ionophoric antibiotics can be exploited as novel anti-obesity therapeutics", but until that has been done and we know which other cells' differentiation they may inhibit, as well, I'd strongly discourage anyone from 'supplementing' with the antibiotics from his or her poultry farmer next door. After all, you may well end up not just with less body fat, but with less brain tissue, as well... what? You don't care? Oh I see. The doctor must have inserted the cannula into your ears instead of your belly on your last liposuction, right?
  
• Alpinia officinarum, a plant in the ginger family, stops fat gains in its tracks (Jung. 2012) -- Jung, Jang, Ahn and the rest of the researchers from the Korea Food Research Institute in Seongnam, report in their latest paper that an ethanol extract from Alpinia officinarum, a plant in the ginger family that's cultivated in Southeast Asia and is also known as lesser galangal, is yet another mainstay of traditional medicine with significant anti-obesity effects.
  
  

  

  It looks almost like ginger and works almost like ginger, but A. officinarum contains galangin, not gingerol and works via the PPAR-gamma pathway, as well. That's something gingerol doesn't do (Huang. 2012)

  Originally used throughout Asia in curries and perfumes, A. officinarum contains a dietary flavenol called galangin, which has already been shown to exert profound anti-cancer effects (Kapoor. 2012), whether it is solely responsible for the in vitro and in vivo inhibitory effects on lipid accumulation during the differentation of 3T3-L1 adipocytes is not certain, but appears to be likely.
  
  Via its effects on the fat synthesis and breakdown and PPAR-gamma activity the A. officinarum extract (AOE) lead to dose-dependent decreases in body weight gains of mice who were fed a high fat diet. It also reduced the visceral and liver fat deposition and partially restored the abnormally elevated insulin and leptin levels of the rodents.
  

  "Collectively, these results suggest that AOE prevents obesity by suppressing adipogenic and lipogenic genes. AOE has potential for use as an antiobesity therapeutic agent that can function by regulating lipid metabolism." (Jung. 2012)

  Certainly another nice find, but let's be honest, what's the real value of all this herbs? I mean yeah they work almost as effectively (in some cases even better) than pharmacological drugs, but both share a detrimental downside, that's not mentioned under "side effects" on the package insert or supplement bottle: They will only manage a problem the root course of which is the net result of a totally messed up diet.

That's it and since you've gotten the bottom line in advance and another time, just to make sure nobody can over-read it, in the last paragraph of the last news item, I just want to remind everyone that there are a couple of other interesting science news and links, for example about ...

• the pro-carcinogenic effects of shift work and to a lesser degree constantly working at night (read),
• the connection between high GI carbs and prostate cancer (read), or
• the idiocy of battling the high GI carb induced decline in cognitive performance with even more sugar (read)

waiting for you on Facebook. Have a nice day and get lean and stay lean ;-)

References

• Huang TH, Teoh AW, Lin BL, Lin DS, Roufogalis B. The role of herbal PPAR modulators in the treatment of cardiometabolic syndrome. Pharmacol Res. 2009 Sep;60(3):195-206. Epub 2009 Apr 7.
• Huczyński A, Janczak J, Antoszczak M, Wietrzyk J, Maj E, Brzezinski B. Antiproliferative activity of salinomycin and its derivatives. Bioorg Med Chem Lett. 2012 Dec 1;22(23):7146-50.
• Jung CH, Jang SJ, Ahn J, Gwon SY, Jeon TI, Kim TW, Ha TY. Alpinia officinarum Inhibits Adipocyte Differentiation and High-Fat Diet-Induced Obesity in Mice Through Regulation of Adipogenesis and Lipogenesis. J Med Food. 2012 Nov;15(11):959-67.
• Kapoor S. Galangin and its emerging anti-neoplastic effects. Cytotechnology. 2012 Oct 25.
• Kirchner H, Hofmann SM, Fischer-Rosinsky A, Hembree J, Abplanalp W, Ottaway N, Donelan E, Krishna R, Woods SC, Müller TD, Spranger J, Perez-Tilve D, Pfluger PT, Tschöp MH, Habegger KM. Caloric restriction chronically impairs metabolic programming in mice. Diabetes. 2012 Nov;61(11):2734-42. doi: 10.2337/db11-1621.
• Petäjä EM, Sevastianova K, Hakkarainen A, Orho-Melander M, Lundbom N, Yki-Järvinen H. Adipocyte size is associated with NAFLD independent of obesity, fat distribution and PNPLA3 genotype. Obesity. 2012. Ahead of Print.
• Saad A, Dalla Man C, Nandy DK, Levine JA, Bharucha AE, Rizza RA, Basu R, Carter RE, Cobelli C, Kudva YC, Basu A. Diurnal pattern to insulin secretion and insulin action in healthy individuals. Diabetes. 2012 Nov;61(11):2691-700.
• Szkudlarek-Mikho M, Saunders RA, Yap SF, Ngeow YF, Chin KV. Salinomycin, A Polyether Ionophoric Antibiotic, Inhibits Adipogenesis. Biochem Biophys Res Commun. 2012 Oct 31.
• Tzeng TF, Lu HJ, Liou SS, Chang CJ, Liu IM. Reduction of lipid accumulation in white adipose tissues by Cassia tora (Leguminosae) seed extract is associated with AMPK activation. Food Chem. 2013 Jan 15;136(2):1086-94. doi: 10.1016/j.foodchem.2012.09.017.