Interaction of Fat Cell Size, Protein Intake & Co. W/ Fat Gain + Insulin Res. in Overfed Men + Women in Metabolic Ward

That's rather the low protein variety of overfeeding... but wait, was the high protein diet even "high" in protein? Well high enough to affect liver fat, for sure.

You will probably remember José Antonio's high protein overfeeding study series (learn more) from the articles here and on the SuppVersity Facebook page. The results were quite impressive, but the number of controlled covariates were small and the dietary control was limited to food logs.

In a more recent study, George A. Bray and colleagues from the Pennington Biomedical Research Center of the Louisiana State University System, the George Mason University, and the FL Hospital & Sanford-Burnham Prebys Discovery Research Institute (Bray. 2016) determined the effect of overfeeding diets with 5%, 15% or 25% energy from protein on glycemia + body fat distribution in healthy men and women with add. covariates and in a metabolic ward.

Yes, the high protein intake clogged the liver during overfeeding

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In total, 15 men and 5 women were overfed by 40% (extra calories above maintenance) for 56 days with diets containing

• 5% (LP) of the total energy as protein, 
• 15% (NP) of the total energy as protein, or 
• 25% (HP) of the total energy as protein

Insulin sensitivity was measured using a two-step insulin clamp at baseline and at 8 weeks. Body composition and fat distribution were measured by DXA and multi-slice CT scan ... so far not so different, but the subjects were contained in a metabolic ward, cheating on the diet was thus as impossible, as taking supplements or working out like maniacs.

Figure 1: Diagram that illustrates the 8-weekstudy design; N = 10 male, 5 female subjects (Bray. 2016).

In conjunction with the scientists' analysis of the subjects abdominal subcutaneous fat cell size, which was determined on osmium fixed fat cells, these are two strengths of a study, of which it is yet quite obvious that it also had its disadvantages:

• 

  Review the effects of different macronutrients in overfeeding studies | more

  the protein content of the diet is simply hilarious - that's not just because eating 5% protein, only is nothing but idiotic, but also because 25% of protein is far away from what can be considered "high protein" these days;
• the lack of exercise limits the significance of the results - at least for the majority of SuppVersity readers overeating in phases in which you don't exercise is probably nothing they would even remotely consider.

The scientists observations that neither the subjects' insulin sensitivity and free fatty acids during low and high levels of insulin infusion did not differ after 8 weeks of overfeeding.

Figure 2: Effect of 8 weeks of overfeeding on abdominal fat distribution, ectopic lipid; rel. changes (Bray. 2016).

What did differ, however, were the changes in body fat distribution according to DXA and how the latter depended on the protein content on fat cell size before the overfeeding period. More specifically, ...

• the fat free mass (FFM) and intrahepatic lipid increased more on the high protein, whereas 
• % BF and fasting free fatty acids (FFA) increased more on the low protein diet, while

In addition, the scientists observed that a high initial fat cell size predicted increased visceral fat gains and the FFA suppression during the high-dose insulin clamp.

Figure 3: Relation of Baseline Fat Cell Size to Change in Visceral Adipose Tissue Mass with Eight Weeks of
Overfeeding in heathy volunteers (VAT 0.040 +/- 0.70(FCS); P < .0063 | Bray. 2016)

The subjects' insulin levels at baseline, on the other hand, predicted the increase in subcutaneous but not visceral fat accumulation (see Figure 3) - most intriguingly with low fasting insulin
at baseline correlated predicting higher changes in % fat (for insulin the scientists observed a correlation with r = –0.43; P < .034), but not with other variables. It is thus not surprising that the most insulin sensitive subjects also gained the most subcutaneous fat... or, as the scientists put it: "HOMA IR predicted the increase in DSAT (r = 0.50; P <.016), but not other variables" (Bray. 2016).

Those are important insights of which the authors rightly point out that they clearly indicate that "an induction of insulin resistance with overfeeding is related to fat cell size and requires more than an expansion of adipose tissue stores" (Bray. 2016).

A surprising, but not debatable result of the study at hand is that the high protein diet increased liver fat (HUs;  measured with DXA, too).  The low protein diet, on the other hand, helped to decrease the subjects' liver fat significantly - remember: we are talking about a diet with 40% extra energy on top of the regular diet (Bray. 2016).

Bottom line: Yes, you've read all that in individual articles (albeit often about rodent studies) on SuppVersity before: (1) the more protein, the greater the lean mass gains; (2) the less protein, the greater the ratio of fat to lean mass gains; (3) the fuller your fat cells, the more likely you will gain metabolically unhealthy visceral fat; and (4) the more insulin sensitive you still are, the more metabolically healthier subcutaneous fat you will gain.

What is news, or at least has not been observed in Antonio's study in active individuals (also because they didn't look) is the surprisingly ill effect of high amounts of protein on liver fat (see Figure, right): while the low protein diet reduced the subjects' liver fat sign, the high protein diet triggered a small, but undesirable accumulation of liver fat during overfeeding in normal-weight subjects - not good, but not yet critical and hopefully something you'd not see w/ concomitant exercise or smaller calorie excess | Comment!

References:

• Bray, George A., et al. "Effect of three levels of dietary protein on metabolic phenotype of healthy individuals with 8 weeks of overfeeding." The Journal of Clinical Endocrinology & Metabolism (2016): jc-2016.

Fat-Blocker Effect of Tea Catechins Confirmed (?) in Man - Sign. Abdominal Fat Loss (5-8%) in 12 Weeks W/Out Diet

Tea catechins (which can also be found in black and jasmin tea | see Figure 3) can help you keep particularly unhealthy abdominal fat (Després. 2012) at bay.

It is one thing to have in-vitro and rodent data that green tea can inhibit the digestion of dietary fat (reported previously in the SuppVersity Facebook News); it is another thing, however, to have a human study like the one Makoto Kobayashi and colleagues are about to publish in the peer-reviewed scientific journal Food & Function that shows that the "[i]ngestion of a green tea beverage enriched with catechins with a galloyl moiety (THEA-FLAN 90S) during a high-fat meal reduces body fat in moderately obese adults" (Kobayashi. 2015).

Ok, the abdominal fat loss does not, as the previous quote from the conclusion appears to suggest, occur instantly right after you've consumed your first tea w/ a single meal.

You can learn more about green tea at the SuppVersity

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Will Drinking Tea Solve Your Sugar Problem?

Rather than that, 124 subjects (two of the initially 126 subjects 2 dropped out for personal reasons unrelated to the trial), 53 men, 71 women, who consumed similar, albeit non-standardized diets (see Figure 1 | note: physical activity was also identical) and began the study with body fat levels of ca. 31-35% had to consume the previously mentioned tea beverage that contained tea catechins (250 mL with 215.3 mg green tea catechins containing 211.0 mg green tea catechins with a galloyl moiety) twice or three times daily during mealtimes for 12 weeks, before the significant reduction in body fat became visible.

Figure 1: Macronutrient composition (in g an % of energy) of the non-energy reduced diets the subjects consumed; the values in the left pie chart represent a group average of all three intervention groups. Since the data is based on food records with photographs, it is probably more reliable than in your average diet study (Kobayashi. 2015).

Now, in view of the fact that this is not the first study to demonstrate weight loss effects in overweight subjects consuming green tea or, as in most other studies, green tea extracts, the word "during" and thus the fact that the green tea beverage was consumed with at least two of the three meals per day should be highlighted as a specific feature of the study at hand that is highly relevant to its interpretation.

Figure 2: Detailed analysis of the rel. change in fat area in the abdominal depot of the subjects (Kobayashi. 2015)

It is after all the requirement that the green tea beverage had to be consumed with a (preferable high fat) meal that allows the authors to conclude that the significant fat loss Kobayashi et al. measured by the means of computer tomography predominantly in the abdominal area are the result of an inhibition or slowing of the intestinal fat absorption and thus warrant the conclusion that "the ingestion of green tea beverages enriched with CGM together with high-fat meals may be an effective strategy for reducing body fat in moderately obese adults" (Kobayashi. 2015) - an observation of which I would like to add that the underlying mechanism is not 100% certain.

What about weight and, even more importantly, muscle loss? No, losing lean mass was not an issue in, because weight loss (-0.6 and -0.8% in the low and high dose group, respectively | measured by bio-electrical impedance vs. computer tomography as it was the case for the abdominal fat area) was actually not an issue, either. If you want to measure your success on the scale, green tea is thus not going to be the "diet tool of choice" (unless you use it alongside an energy-reduced diet)... however, if you take into account that the placebo group actually did what the average Westerner does, these days, i.e. gain weight and body fat over the 12-week study period, you may argue that you can still see the results on the scale which could finally stand still after years of displaying subtle, but eventually relevant increases in body weight.

The authors base their conclusion that it is "unlikely that absorbed green tea CGM leads to increased energy expenditure, followed by reduced abdominal body fat area" (Kobayashi. 2015) on two reasonable, but experimentally (in this study) not confirmed assumptions which are that little to no catechins actually made it into the bloodstream, because ...

1. the low caffeine content of the beverage limits the bioavailability of EGCG & co (caffeine enhances its bioavailability | Nakagawa. 2009) and
2. the ingestion of the beverage with a meal has been shown to significantly reduce the bioavailability of green tea catechins in comparison to the fasted state (Chow. 2005).

The assumption that its just a blockade of the digestion of fat becomes even more questionable, if you (re-)read my 2014 article on the carb blocking effects of tea... Well, eventually, though, you may argue that it does not matter if the reduction in abdominal fat was due to thermogenic effects, thermogenic and fat-blocking effects or, as the scientists believe, mediated exclusively an "inhibit[ion] or slowing [of the subjects'] intestinal fat absorption" (Kobayashi. 2015). And let's be honest, I guess you're right. What matters is that there were significant reduction ins abdominal fat (visceral, subcutaneous and total abdominal fat area). Reduction of which the data in Figure 2 tells you that ...

1. 

   Table 1: Catechin composition of the test beverages.

   the fat loss in the abdominal area was dose dependent - even if the differences between the low and high dose group did not reach statistical significance (for the exact catechin composition see Table 1 on the right) - and that 
2. roughly 50% of the benefits were lost within only 5 weeks when the subjects stopped consuming the green tea beverage, even though their diet didn't change at all (in fact, they consumed minimally less energy in the withdrawal phase from week 12-17).

Now, (b) is obviously good news for green tea lovers, but bad news for those who cannot imagine consuming green tea containing beverages "for the rest of their lives".

Green tea forever, it is then!? Well, as usual we have to consider what limits the generalizability of the results. Firstly, we are dealing with a group of people who have more than a few pounds of extra-weight on their hips. An abdominal fat loss of 8% in 12 weeks is thus not impossible, but not exactly likely to be seen in someone who starts at a body fat percentage of 15% or less (which is half what the subjects in the study at hand began with).

Figure 3: Catechin content (mg/10ml) of black, green and jasmine tea prepared from commercial tea w/ different infusion times (Bronner. 1998).

The second thing we have to keep in mind is the beverage itself. As you've previously read, it has been enhanced with catechins with a galloyl moiety (CGMs | EGCG, ECG, GCG, CG). Does this mean that you cannot achieve similar results if you simply drink green tea? Luckily, data from Bronner, et al. (1998) suggests otherwise. As you can see in Figure 3, it would take only 100 ml of commercially available freshly brewed (infusion time 3 min) green tea and even less black tea to achieve similar concentrations of EGCG and the other catechins with a galloyl moiety in your tea. Accordingly, the second obstacle to the gene- relizability of the study is actually irrelevant.

Third- and lastly, there's yet still the fast reversal of the effects which suggests that it is necessary to become a habitual tea drinker to see long-term / lasting benefits of green tea (or as the data in Figure 3 suggests even catechin containing tea in general) on your body weight and, more importantly, body fat you're carrying around | Comment on Facebook!

References:

• Bronner, W. E., and G. R. Beecher. "Method for determining the content of catechins in tea infusions by high-performance liquid chromatography." Journal of Chromatography A 805.1 (1998): 137-142.
• Chow, HH Sherry, et al. "Effects of dosing condition on the oral bioavailability of green tea catechins after single-dose administration of Polyphenon E in healthy individuals." Clinical Cancer Research 11.12 (2005): 4627-4633.
• Després, Jean-Pierre. "Body fat distribution and risk of cardiovascular disease an update." Circulation 126.10 (2012): 1301-1313.
• Kobayashi, Makoto, et al. "Green tea beverages enriched with catechins with a galloyl moiety reduce body fat in moderately obese adults: a randomized double-blind placebo-controlled trial." Food & Function (2016).
• Nakagawa, Kiyotaka, et al. "Effects of co-administration of tea epigallocatechin-3-gallate (EGCG) and caffeine on absorption and metabolism of EGCG in humans." Bioscience, biotechnology, and biochemistry 73.9 (2009): 2014-2017.

More Aerobics, More Subcutaneous, Yet not More Visceral Fat Loss - Despite or Because of Higher Energy Intakes?

Visible abs require low subcutaneous, not visceral fat levels: Why? Well, despite being located at the midsection, the nasty fat covering your abs is subcutaneous.  

I should probably call today's SuppVersity article a "classic"; not because it was published in this form before, but rather because it is based on a paper that has been accepted for publication back in 1997. In view of the fact that the question its authors sought to answer is as topical today as it was in the late 1990s, though, I thought it may be worth writing a brief article about Takahashi Abe's quest for relationship between training frequency and subcutaneous and visceral fat loss in women (Abe. 1997). As Abe et al. point out, their study was "designed to investigate the effect of varying frequencies of aerobic exercise training and caloric restriction on [visceral fat mass] and [subc. fat mass]" (Abe. 1997).

In that, the scientists speculated that due to the increased energy expenditure the 13 women who had been randomly assigned to the 3-4 sessions per week group should lose significantly more subc. and visceral fat than their pendants who went to the gym only 1-2 times per week.

You can learn more about cardio at the SuppVersity

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During the complete study period subjects were advised to cut their energy intake by 200kcal/day and perform 30 min of medium-intensity cardio at 50-­60% of their individual maximal heart rate reserve (0.5≈0.6 [maximal pulse ­ resting pulse] + resting pulse) as calculated from a maximal exercise test. With the same baseline dietary deficit, the 3-4SW group would thus have a significantly more pronounced weekly caloric deficit than the 1-2SW group if all subjects stuck to their diets and their otherwise sedentary lifestyle.

Energy deficit - contribution of exercise vs. diet (Abe. 1997).

No diet = better weight loss? Now what is particularly interesting is that the high frequency training group 2-3SW did not not achieve the prescribed 200kcal (~15%) reduction in energy intake - and that despite the fact that the 3-4SW group only trained 2.8x per week (you see, adherence is a problem in scientific studies, too). If we do the math on intake vs. output, the 1-2SW group actually had a more pronounced deficit than the 3-4SW group. Against that background it's all the more surprising that they achieved a significantly more pronounced reduction in subcutaneous body fat (-16.2% vs. -4.9%) - even if we take into account that the calculations do not account for potential reductions of the basal metabolic rate in the dieting 1-2SW group.

As you already know from the headline, though, the expected difference showed only for the subcutaneous (that's the fat you actually see hanging around), yet not for the visceral (inter-organ) fat (see Figure 1) which was actually (non-significantly) more reduced in the 1-2SW group.

Figure 1: Changes in subc. and visceral fat over the course of the 13-wk study period (Abe. 1997).

Seeing that fat depots don't melt at the same speed is and was by no means news, though. And the difference doesn't exist for visceral vs, subcutaneous fat, but also for different subcutaneous fat depots.

Despres et al. (1985) for example found almost 2x higher rates of trunk fat vs. extremity fat loss in young men who lost 2.6kg of body fat over the course of a a 20­ wk aerobic exercise training program. Likewise in contrast to the results of the study at hand, a 9­ to 12­ month aerobic exercise training program on sedentary older men and women, that was conducted by scientists from the Washington University School of Medicine St. Louis showed a significantly greater reduction of upper trunk vs. extremityfat. (Kohrt. 1992).

So, do you do cardio to cut subc. and strenght to cut visceral fat? Both observations are mirrored in the study at hand, where the ladies lost sign. more SFM in the truncal segment compared with the limb segments, but they stand in contrast to the observations Treuth et al. made in a similarly designed study, in which the slightly older female study participants did yet not do 30 min of medium intensity steady state cardio, but rather upper and lower body resistance training.

If we compare the results of cardio (e.g. Abe, 1997, Kohrt, 1992) and strength training studies like the one by Treuth et al. (1995) from which I took the data in the figure above, it looks as if weights were the better visceral, while low-to-medium-intensity steady state cardio exercise the better subc. fat burner... well, on average.

With significant reductions in visceral (intra-abdominal), but only negligible reductions in subcutaneous fat, a comparison of the results of the study at hand with the Treuth-study does in fact suggest that strength training may have an edge over low(er) intensity steady state cardio when it comes to getting rid of the unhealthy fat in ones midsection.

What I would doubt, though, is that the same difference would be seen for resistance vs. HIIT or resistance vs. high intensity cardio training. Generally speaking, though, this difference appears to confirm another old bodybuilding mantra which is to combine intense strength training and relatively light, but frequent cardio training before stepping on stage. If we go by the results of the studies discussed in this article, as well as the STRIDE trial which shows reduced visc. fat with low volume and reduced visc. and subc. fat with higher amounts of exercise (Slentz. 2005), it does look as if high (not insane) volume cardio + high intensity weights was another reasonable bodybuilding practice.

And while the role of the total energy deficit still requires investigation it appears as if dieting would be the prerequisite to lose the unhealthy visceral fat, the extent of the deficit appears to be less important than exercise when the reduction of unaesthetic, but comparatively benign subcutaneous body fat is what you want to lose. One thing I can tell you without further research, though, is that the "last fat" is not going to go without a reduction in energy intake | Comment on Facebook!

References:

• Abe, T., et al. "Relationship between training frequency and subcutaneous and visceral fat in women." Medicine and science in sports and exercise 29.12 (1997): 1549-1553.Després, J. P., et al. "Effects of aerobic training on fat distribution in male subjects." Medicine and science in sports and exercise 17.1 (1985): 113.
• Kohrt, Wendy M., Kathleen A. Obert, and John O. Holloszy. "Exercise training improves fat distribution patterns in 60-to 70-year-old men and women." Journal of gerontology 47.4 (1992): M99-M105.
• Slentz, Cris A., et al. "Inactivity, exercise, and visceral fat. STRRIDE: a randomized, controlled study of exercise intensity and amount." Journal of Applied Physiology 99.4 (2005): 1613-1618.
• Treuth, MARGARITA S., et al. "Reduction in intra-abdominal adipose tissue after strength training in older women." Journal of Applied Physiology 78.4 (1995): 1425-1431.

Battling Fat W/ Fat: Subcutaneous Fat Implant Improves Glucose Tolerance and Alleviates Inflammation | Plus: Beware of the Potential Ill Health Effects of Liposuction

BMI is not a good predictor of metabolic health. One reason it isn't is the differential contribution of visceral and subcutaneous body fat on diabesity an CVD risk. The rodent study at hand demonstrates that quite drastically.

It is absolute bogus to deny the contribution of the ever-increasing amount of fat many of us are carrying around day by day to all sorts of potentially fatal diseases. In that, it is yet important to differentiate between the accumulation of intra-abdominal or visceral adipose tissue (VAT) which is associated with type 2 diabetes, dyslipidaemia and hypertension and high amounts of subcutaneous fat which are (comparatively "benign").

As Hocking et al. (2014) highlight in their latest paper, "[t]his relationship [between VAT, type 2 diabetes, dyslipidaemia and hypertension] was originally attributed to increased NEFA [non-esterified fatty acid] flux from VAT into the portal circulation" (Hocking. 2014).

HIIT is an excellent way to shed both subcutaneous and visceral body fat!

Never Train To Burn Calories!

Tabata = 14.2kcal /min ≠ Fat Loss

30s Intervals + 2:1 Work/Rec.

Making HIIT a Hit Part I/II

Making HIIT a Hit Part II/II

HIIT Ain't For Everyone

A closer look at the low relative contribution of VAT to the total NEFA concentration in our blood does yet suggest that other factors, such as the proinflammatory cytokine production that is particularly pronounced in visceral (vs. subcutaneous) would be at least as important as the constant efflux of non-esterified fatty acids.

To probe the differential acute and chronic effects of subcutaneous (non-inflammatory) and visceral adipose tissue on glucose metabolism and whole body inflammation, researchers from the Garvan Institute of Medical Research in Australia conducted an interesting experiment in which they performed time course studies to investigate the short- and long-term effects of inguinal subcutaneous→visceral (SubQ→Vis) and  epididymal visceral→visceral (Vis→Vis) adipose tissue transplantation in HFD-fed mice.

Figure 1: The transplantation of subcutaneous fat into the intra-abdominal cavity of the mice did not just improve the glucose tolerance it did also (albeit non-significantly) blunt the HFD-induced weight gain (Hocking. 2014).

Yes, it may sound hilarious, but instead of removing intra-abdominal fat, the scientists transplanted subcutaneous or visceral fat into the abdominal cavity of their lab animals. Ca. 150-225mg of fat that's tantamount to 13% of their total body fat that was thus redistributed.

Yes, the study at hand does also underline the fallacies of liposuction: Unlike lifestly-induced weight loss that will target both visceral and subcutaneous body fat (for the obese the visceral fat will usually go first), liposuction will remove only subcutaneous fat. It is thus not surpFrising that liposuctions will have no effect on insulin action and risk factors for coronary heart disease (Klein. 2004). With significant increases of 16% (range 13 to 21 percent) in women and 13 (10-17%) of the visceral to subcutaneous fat ratio, as they were observed by Matarasso et al. (1998), and post-liposuction gains in total visceral fat, the removal of unaesthetic subcutaneous fat may eventually even worsen a patients' metabolic health (assuming the liposuction is not complemented by profound lifestyle changes | no energy surplus, no fat gain!).

Now, what is intriguing, though, is that "sick" were only those rodents who had been transplanted with metabolically active and highly inflammatory visceral fat. The rodents who harbored an additional 13% of formerly subcutaneous fat in their abdominal cavity actually experienced significant improvements in glucose tolerance and inflammation within the 6 week post-transplantation study period and that despite the fact that they received the same obesogenic high energy + high fat diet as the rodents who were sham operated or received visceral donor fat.

A closer examination of the underlying mechanisms revealed that the SAT transplantation prevented HFD-induced hepatic triacylglycerol accumulation and normalised the expression of hepatic gluconeogenic enzymes.

"Grafted fat displayed a significant increase in glucose uptake and unexpectedly, an induction of skeletal muscle-specific gene expression. Mice receiving subcutaneous fat also displayed a marked reduction in the plasma concentrations of several proinflammatory cytokines (TNF-α, IL- 17, IL-12p70, monocyte chemoattractant protein-1 [MCP-1] and macrophage inflammatory protein-1β [ΜIP-1β]), compared with sham-operated mice. Plasma IL-17 and MIP-1β concentrations were reduced from as early as 4 weeks after transplantation, and differences in plasma TNF-α and IL-17 concentrations predicted glucose tolerance and insulinaemia in the entire cohort of mice (n=40)" (Hocking. 2014).

That's in contrast, mice receiving visceral fat transplants who were glucose intolerant, with increased hepatic triacylglycerol content and elevated plasma IL-6 concentrations.

Being heavy is not the problem. The problem is being fat. Even if your BMI is in rance, men and women with body fat levels >25% / 35%, respectively have significantly increased risks of developing one or all of the central features of metabolic syndrome (Oliveros. 2014) 

Is this a viable treatment option for humans? Probably not, but the results of the study at hand highlight the often overlooked of invisible intra-abdominal fat. Specifically women appear to be at high risk of being "skinny at" or "normalweight obese", which means that they have a normal BMI but body fat levels far above the normal range of <30%. As the data from a 2014 study by scientists from the Mayo Clinic in Rochester indicates, their risk of suffering from one or even all of the features of the metabolic syndrome is significantly increased.

Specifically for this group of subjects, a subcutaneous → visceral fat transplant may actually alleviate he symptoms, but whether that's a sensible treatment option is more than questionable. Rather than that, diet and exercise the unbeloved standard recommendations are still the way to go. In conjunction they are the #1 visceral fat burner - with meds being necessary only for the severely obese to bring the into a situation where they are actually able to adhere to the necessary lifestyle interventions | Comment on Facebook!

References:

• Hocking, Samantha L., et al. "Subcutaneous fat transplantation alleviates diet-induced glucose intolerance and inflammation in mice." Obesity Research & Clinical Practice 8 (2014): 99-100.
• Klein, Samuel, et al. "Absence of an effect of liposuction on insulin action and risk factors for coronary heart disease." New England Journal of Medicine 350.25 (2004): 2549-2557.
• Matarasso, Alan, Richard W. Kim, and John G. Kral. "The impact of liposuction on body fat." Plastic and reconstructive surgery 102.5 (1998): 1686-1689.
• Oliveros, Estefania, et al. "The concept of normal weight obesity." Progress in cardiovascular diseases 56.4 (2014): 426-433.

30 Min of Exercise Can Avoid Costly & Unhealthy Gestational Diabetes. Carbohydrate Oxydation Determines Appetite After Workouts. Using a Measuring Tape to Judge Visceral Fat Mass. Update: Vitamin D, Age & Obesity.

85 sessions (general fitness class, three times/week, 55-60 min/session from weeks 8-10 to weeks 38-39 of pregnancy are nothing but healthy for mother + child (Barakat. 2013)

Obese mothers with gestational diabetes are more than just a financial burden. That's what the SuppVersity Figures of the Week clearly indicate.

According to a recently published paper from the National University of Ireland Galway woman who develop gestational diabetes during pregnancy (mostly due to pre-existing extra fat-pounds; not BMI), produce 34% higher health-care costs (Gillespie. 2013). Just as the 75% increase in the necessity to have the kids being delivered by cesarean section, this would still be tolerable, though, if their poor offspring did not also have a increased risk of being born with pathological ventricular hypertrophy (Ullmo. 2007) and a 214% higher likelihood of having to be admitted to the neonatal unit, which, in turn, is associated with "increased and/or aberrant adiposity, in addition to postnatal growth retardation" (Gianni. 2012).

Another good reason to (a) get healthy (and contrary to what the soothing news in the mainstream media will tell you this involves having normal body fat levels), before you even think of bringing a baby into this world and (b) not dropping your exercise regimen all-together, when you're pregnant:

 "A supervised program of moderate exercise performed throughout pregnancy is not a risk of preterm delivery for heal thy pregnant women." (Barakat. 2013) 

This, by the way, works not only in type II, but also type I diabetic mothers, whose chance of developing gestational diabetes and/or even more hazardous extreme spikes and troughs in blood glucose can be reduced from 19% to ZERO with only 30 min of light exercise per day (a self-paced walk in the park is enough!) and making the right food choices (Kumareswaran. 2013).

• Related D-News from Japan: Vitamin D deficiency in Japan comes with current smoking, being female, lack of regular walking and low dietary vitamin D intake, study shows (Yoshimura. 2013).
  

  Overall, 81.3% of the subjects in the study from the University of Tokyo were vitamin D insufficient - only 1.2%, though, had a full-blown deficiency, defined as 25OHD levels below 10 ng/ml.
  Being fat is a critical determinant of baseline vitamin D levels and the response to vitamin D supplement in older Irish adults (Forsythe. 2013).

  "In older adults, vitamin D status was inversely associated with BMI (kg/m2), WC (cm), FM (kg and %), FMI (kg/m2) and FM:FFM (%) at baseline (r − 0·33, − 0·36, − 0·33, − 0·30, − 0·33 and − 0·27, respectively, all P values < 0·01). BMI in older adults was also negatively associated with the change in 25(OH)D following supplementation (β − 1·27, CI − 2·37, − 0·16, P = 0·026)."

  What's surprising, though, is the fact that this correlation of which I have previously argued that is is probably based on the pro- and anti-inflammatory effects of obesity and vitamin D and initiated by being fat, not vitamin D deficient, was not present in the younger study participants.
  
  Just as a review I mentioned only a couple of days ago said: There is still much to learn about vitamin D - in that case D2 & D3 - and how their enzymatic hydroxylation influences both our baseline levels as well as their metabolic downstream effects (read more)

• Exercise does not make you hungry, per se, but the more carbs you burn during your workout the hungrier you're gonna be afterwards (Hopkins. 2013) That's the main finding of a recent study from the Leeds Trinity University in the UK.
  
  

  

  There comes a time, when getting fat and sick is no longer only about making the "wrong" food choices or a non-warranted urge to eat. A time, when neither the apple nor granny's pie will satisfy your hunger, and your cells will be starving within a nutritious cocktail of partially oxidized fatty acids and sticky glucose molecules... yet still, or I should say, exactly for that reason simply "cutting calories" won't solve the problem. Learn more about how this state is creeping up on the obesity generation (read more)

  According to the data the researchers gathered in the course of a bout of cycling individually tailored to expend 400 kcal (EX) or a time-matched no exercise control condition in a randomized, counter-balanced order,
  

  "[...] there was a marked individual variability in compensatory EI. The difference in EI between EX and the control condition ranged from -234.3 to 278.5 kcal. Carbohydrate oxidation during exercise was positively associated with postexercise EI, accounting for 37% of the variance in EI (r=0.57; p=0.02)" (Hopkins. 2013)

  That's particularly interesting, because the average total energy intake did not differ significantly between the exercise and the control condition (666.0±203.9 vs 664.6±174.4 kcal, respectively) in the overweight and obese women with a mean BMI of 29.6±4.0 kg/m².
  
  These observations provide further evidence of the detrimental effects of metabolic inflexibility, a classic characteristic of developing or full-blown metabolic syndrome and a state in which your body is heavily (in the worse cases almost exclusively) reliant on glucose as a substrate - a paradox, in view of the fact that thee aberrant insulin resistance of obese individuals has their cells starve in a state of glucose abundance (learn more)

• Toss your scale and use a measuring tape! Nothing predicts metabolic risk and high risk visceral fat as adequately as the circumference of your midsection (Grundy. 2013)
  
  As a SuppVersity reader you should actually have banned your scale into the depth of your "things I will never need again (!)"-cupboard, once you achieved a normal body weight (on a side note: I don't have a functional scale). From the many questions I receive on a daily basis, I do yet know that some of you are either hesitant to do that or fill inclined to get it back out from time to time to ruin their days and results by stepping on the scale at least thrice a week. If that's you, I suggest you take a peak at the results of a recent study from the Clinical Nutrition and Center for Human Nutrition and the Division of Cardiology of the University of Texas Southwestern Medical Center in Dallas.
  
  To find out whether or not a simple measuring tape by the means of which you would assess the circumference of your waist (WC) would be an adequate measure of total abdominal fat (TAF), abdominal subcutaneous fat (ASF) and intraperitoneal fat (IPF) Scott M. Grundy and his colleagues correlated the measuring tape data with results they had obtained from magnetic resonance imaging (MRI) and found an excellent correlation between WC and total abdominal fat (R² = 0.81 − 0.88) "with progressively lower correlations with ASF (0.65–0.82) and IPF (0.29–0.85)" (Grundy. 2013)
  

  

  Figure 1: Median intra-abdominal fat (median in kg), waist circumferences and corresponding intraperitoneal to total abdominal fat rario (IP/ABS x10) for quintile 1-5 of total abdominal fat in men (left) and women (Gruny. 2013)

  As hinted at in the arrow in figure 1 the accuracy of the waist circumference as a means to quantify the body fat levels and metabolic risk does not only depend on gender, but also on ethnicity, with African American men and women having lower median IPF masses than Whites and Hispanics, in general, but high(er) greater amounts of subcutaneous. In view of the fact that unlike IPF, ASF correlated only with HOMA2-IR, whereas elevated IPF values were also reliable predictor of high triglyceride levels, as well - African Americans may be at a slightly, but probably not significantly lower risk of developing heart disease (high triglycerides are a neat predictor here) than Whites and Hispanics of whom the latter tend to carry the most vicious visceral fat per cm on their waists.

Believe it or not, but that's it for today! I know that was fast and therefore I'll provide you with a couple of additional facebook news, you may be interested in.

• 

  The fact that simply dropping the weight and lying around for weeks could lead to fat gains is actually not that surprising right? So what can be done to make constant progress without overtaxing the system? One of the answers certainly is P-E-R-I-O-D-I-Z-A-T-I-O-N and the Step By Step Guide to Your Own Workout Routine is the series, where you can learn about planning your training schedule in the long and short run to maximize your results and accommodate it to your personal goals (read more)

  Is giving up physical culture worse for your health than being a sedentary slob in the first place Rodent study suggests there is propensity for increases in visceral fat gain during 4-week detraining that surpasses in previously trained rats that of the sedentary controlled (read more)
• Fooled again 2.0: By one way or another Subway bamboozles customers to believe their junkfood was less junky than that of the competition. According to a recent Harvard study, adolescents dining at Subway underestimate the caloric value of their nutrient deficient junk food by more than 500kcal! That's... (read more)
• The "starve yourself to live longer"-bubble is bursting! Now scientists realize that even in yeast, what you eat is more important than how much you eat and that the simple addition of a pH buffer can go a long way (read more)
   
• SuppVersity Suggested Read: Prolotheraphy? Can you actually HEAL those chronically painful tendons, ligaments and cartilage without having to resort to a butcher's... ah, I mean a surgeon's knife? My buddy Sean Casey just posted part II of his scientifically grounded answer (read more).

Now that you're through with these as well, all that's left to be said is: "Have a nice weekend, everyone, and don't forget that the SuppVersity is open on Sundays, as well!"

References:

• Barakat R, Pelaez M, Montejo R, Refoyo I, Coteron J. Exercise Throughout Pregnancy Does Not Cause Preterm Delivery. A Randomized, Controlled Trial. J Phys Act Health. 2013 May 10.
• Forsythe LK, Livingstone MB, Barnes MS, Horigan G, McSorley EM, Bonham MP, Magee PJ, Hill TR, Lucey AJ, Cashman KD, Kiely M, Strain JJ, Wallace JM. Effect of adiposity on vitamin D status and the 25-hydroxycholecalciferol response to supplementation in healthy young and older Irish adults. Br J Nutr. 2012 Jan;107(1):126-34. 
• Giannì ML, Roggero P, Piemontese P, Orsi A, Amato O, Taroni F, Liotto N, Morlacchi L, Mosca F. Body composition in newborn infants: 5-year experience in an Italian neonatal intensive care unit. Early Hum Dev. 2012 Mar;88 Suppl 1:S13-7.
• Gillespie P, Cullinan J, O'Neill C, Dunne F; ATLANTIC DIP Collaborators. Modeling the independent effects of gestational diabetes mellitus on maternity care and costs. Diabetes Care. 2013 May;36(5):1111-6. 
• Kumareswaran K, Elleri D, Allen JM, Caldwell K, Westgate K, Brage S, Raymond-Barker P, Nodale M, Wilinska ME, Amiel SA, Hovorka R, Murphy HR. Physical Activity Energy Expenditure and Glucose Control in Pregnant Women With Type 1 Diabetes: Is 30 minutes of daily exercise enough? Diabetes Care. 2013 May;36(5):1095-101. 
• Ullmo S, Vial Y, Di Bernardo S, Roth-Kleiner M, Mivelaz Y, Sekarski N, Ruiz J, Meijboom EJ. Pathologic ventricular hypertrophy in the offspring of diabetic mothers: a retrospective study. Eur Heart J. 2007 Jun;28(11):1319-25.
• Yoshimura N, Muraki S, Oka H, Morita M, Yamada H, Tanaka S, Kawaguchi H, Nakamura K, Akune T. Profiles of vitamin D insufficiency and deficiency in Japanese men and women: association with biological, environmental, and nutritional factors and coexisting disorders: the ROAD study. Osteoporos Int. 2013 May 15.

What's Worse: YoYo-Dieting or Constant Gluttony? What Happens During Weight Cycling? And Why Does Every Diet Make You Fatter? Lots of Questions, a Couple of Answers

Image 1: To eat or to diet, what's worse?

Despite the fact that the magazines are still full of "X pounds in Y weeks" diets, more and more people begin to realize that "diet hopping" and even "dieting" in the conventional sense, i.e. following a special, usually very strict and non-sustainable nutritional regimen for a very short amount of time, are futile. But can calling a halt before you blow up like a balloon from time to time actually be worse than letting yourself go all-day, everyday? According to the results of an experiment that has been conducted at the Institute of Biology of the State University of Rio de Janeiro, the results of which have just been published in the open access journal PLoSOne, the answer to this question must be: YES, it can! And that may be true, even when you are not starving yourself!

Even "healthy" weight cycling turns out to be profoundly unhealthy!

Now, the unfortunate news first: We are, as so often dealing with a rodent study - one that was done conducted with 80(!) 3-months old C57BL/6 mice. "Wow! 80 mice? That's plenty!" Yeah, initially it may sound like that, but in view of the fact that their number was decimated every 8 weeks, there would not have been the necessary 4x8 rodents left at the end of the 24-week study period for the final evaluation of the four experimental groups, which were

• standard chow (SC; 15kJ/g) - rodents in this group received the standard chow (76% energy from carbohydrates, 14% energy from protein, and 10% energy from fats) for the whole study period
• high fat diet (HF; 21kJ/g) - rodents in this group received a fattening hypercaloric diet (26% energy from carbohydrates, 14% energy from protein, 50% energy from animal lard and 10% energy from soy bean oil 
• SC ↔ HF - rodents in this group received standard chow for the first 8-week cycle, high fat diet for the 2nd 8-week cycle and standard chow for the third and last 8-week cycle
• HF ↔ SC - rodents in this group received high fat diet for the first 8-week cycle, standard chow for the 2nd 8-week cycle and high fat  for the third and last 8-week cycle 

If we go back to the initial question, the HF group would be our 24/7, 365 days a year eat everything the worst Western diet you can imagine has to offer, while the animals in the group SC ↔ HF and HF ↔ SC group would be representative of

• the high school football player who turns to a sedentary lifestyle and bad eating habits when he goes to college, is partying all night, bear pizza, etc. eventually, he realizes he got fat, and diets again (SC ↔ HF ↔ SC) and
• the obese kid who eventually turns to physical culture, works out, eats health and loses weight, when he starts college, to then fall back into his old bad habits and starts letting himself go, when he marries and has kids (HF ↔ SC ↔ HF)

I know this is a little far-fetched and as we are going to see later, mice are not exactly the best model to study things like that, but still, the way the weight of the rodents, who had free access to the respective chow they were on during the whole experimental period, developed is quite telling:

Figure 1: Despite intermediate fat loss the increased feed efficiency (=weight gain per kcal) that is especially pronounced in the HF phases of the weight cycling groups quashed the previous weight loss. If age effects had not become a problem this effect would have been more obvious in a 4th cycle.

And the message the data in figure 1 is sending is quite clear: Dieting, as in changing your eating habits only intermediately, is useless, at best! - "at best", because it becomes increasingly difficult to lose and constantly easier to gain weight or, as Barbosa-da-Silva et al. put it:

[...] after three consecutive WC [weight cycles], the reduction of BM is less marked during the SC cycle, as well as the increase of BM is more prominent during HF cycle (Barbosa-da-Silva. 2012).

Now, we probably would not have had to do a 24-week rodent study to know that, right? Right! Notwithstanding, though, the beauty of working with rodents - instead of Biggest Losers, for example - is that they usually don't complain much when you slaughter them, so that the scientist could not only measure the serum leptin (figure 2, left), triglycerides, cholesterol, insulin and glucose levels, but also count the number and measure the size of the adipocytes in their visceral fat pads.

Figure 2: Leptin expression and adipocyte density per area of adipose tissue mass after the 1st, 2nd and 3rd weight gain/loss cycle (data adapted from Barbosa-da-Silva. 2012)

And as you can see in figure 2 (right) the weight cycling induced quite profound effects on the adipose tissue morphology; effects that are similar to what we have seen in previous discussions on the underlying causes of the yoyo effect (see "Nasty Insights into the YoYo-Effect"). You have to keep in mind, though, that you would be comparing apples and oranges if you compare the two weight cycling groups with each other, as one group has always just lost weight, when the other has gained weight so that in one group the adipocytes will  be depleted, when they are filled to the seams in the other one. If there had been a fourth cycle in the course of which the fat cells of the SC ↔ HF group would have been repleted, we may thus safely assume that the absolute size-differences, which reached statistical significance only in the HF ↔ SC group after the third cycle (violette bar in figure 2, right), would have been similar or even more pronounced after 32 weeks and 4 cycles in the then HF dieting SC ↔ HF (note: one of the reasons the researchers did extend the experiment for another 4 weeks was that even now, age-related effects and obesity related morbidities would have reduced the significance of the data).

Adipocyte morphology, leptin expression, fat pad restructuring and body fat that sticks

Apropos significance, you ay remember from the "previously mentioned post" on this issue that one of the currently discussed hypothesis that could  (at least partly) explain why formerly obese people are not just having a really hard time to lose weight, but also, and often even more so, to keep that weight off, relates to what I have previously labeled "relative leptin defiency" (too little leptin production per adipose tissue mass) or, and this would be an alternative hypothesis, "leptin resistance" (more than enough leptin in the blood, but the signal transmission does not work).

The first thing we can say based on the data Barbosa-da-Silva acquired on the absolute fluctuations of leptin in the blood of the rodents (figure 2, left) ist that previously made conclusions about the effects of weight gain, weight loss and energy intake on leptin, like

1. weight loss and fasting are associated with reduced leptin levels, 
2. weight gain is associated with an increase in leptin concentration 
3. chronically increased leptin can lead to leptin resistance
4. meals and according to meal composition or short-term swings in energy balance such as fasting or overfeeding induce swings in systemic leptin levels

appear to be accurate. To check whether there is evidence for my "relative leptin deficiency" hypothesis, especially in weight cycling groups, I ploted the ratio of serum leptin to body fat in figure 3 (left):

Figure 3: Leptin levels in serum per body fat (left), leptin expression in adipose tissue (middle), and sectional area of adipocytes of the different groups (based on Barbosa-da-Silva. 2012)

And what is interesting is that in this calorically non-restricted scenario, the respective "relative leptin deficiency" occurs only in the SC ↔ HF group during the third and last cycle, when their relative leptin levels which should actually be identical to the SC group (we must compare them to the SC group, because the current diet will influence leptin expression as well) are 36% lower than they "should" be. In the same third cycle, the HF ↔ SC group (remember, those are our "formerly obese kids") have 21% more leptin in their blood than they "should" - given their current adipose tissue mass.

Some food for thought - Though not directly related to the topic, there is one thing pertaining to the heavily debated "CLA post" from last week (cf. "CLA Destroys Body Fat"), I want to mention. If we assume that the CLA-induced adipose tissue apoptosis Kim et al. observed in their recent study is as rodent-specific as the natural death and rejuvenation of adipose tissue Cinti et al. observed in the study I cite relating to the limited adipose tissue growth in rodents, this would not just indicate that taking copious amounts of CLA would not help to reverse the damage you may have done during previous "diets", but could also explain why conjugated linoleic acid supplements don't work in humans (or horses; see yesterday's news).

Now this segues directly into the allegedly somewhat counter-intuitive conclusion that anything that soothes the raging inflammation in your fat cells may ameliorate the downstream detrimental effects on glucose and lipid metabolism, but will, on the other hand, help your fat cells to survive or maybe even proliferate in amidst the TNF-alpha induced cytokine storm (Prins. 1997), which would otherwise kill them. Now with the current paradigm of "inflammation = bad" this may sound hilarious. In the the end, it does yet only echo the title of a 1999 paper by Hube and Hauner, "The role of TNF-alpha in human adipose tissue:  Prevention of weight gain at the expense of insulin resistance?" (Hube. 1999) and would provide us with a mechanistic explanation of several otherwise non-explicable phenomena such as the profound fat loss in rodents who lack the master antioxidant glutathion (see "Inflammation Is the True Fat Burner"),,, but as indicated: This is just some food for thought ;-)

In combination with the leptin overshoot (+153%) in the "former football players on their college binge", this data would suggest that we are not dealing with "relative deficiency" and "leptin resistance" but rather with a complex mixture of both, where the latter is probably a result of repeated overshoots like the one we see in the SC ↔ HF group after their first high fat feeding cycle (2nd cycle, 154% elevated leptin levels).

Relative leptin deficiency, systemic resistance and now local differences?

And as if things were nor already complicated enough, there are also potentially important differences between circulating leptin levels and local leptin expression in isolated fat pads figure 3 (middle; compare data to figure 2, left, 3rd cycle). Thus, the drop in leptin levels upon "fasting" in the (SC ↔ HF, 2nd cycle  and HF ↔ SC, 3nd cycle) is systemic, but does not reflect the expression of leptin in the intra-abdominal tissue. This stands in line with my previous dissertation on "relative leptin deficiency" and the differences between...

• intra-abdominal (easy to shed on a diet), and 
• subcutaneous (esp. in the lower body compartment difficult to shed on a diet)

...adipose tissue in "Nasty Insights into the YoYo-Effect" (a similar depot-specificity has been reported for pre-adipocytes, i.e. developing fat cells, as well - intriguingly only in 9 out of human subjects (=81%); cf. Niesler. 1998). Due to the fact that the expansion of adipose tissue in rodents appears to be limited and the cell-turnover high (contrary to humans, where you get the impression that obesity is only limited by death and the cell-turnover - if it exists at all - must be very slow), these effects are probably even more pronounced in humans than in mice. Consequently, it can be expected that the diet / feasting induced upward shifts of the body fat set point are more pronounced and their morphological reversal either more time-consuming (probably true for the visceral body fat) than in rodents or simply impossible (could be the case for parts of the subcutaneous body fat) in human beings.

Image 1 : Lose 20lbs now, gain 25 back and have 5 stick with every diet! We still don't understand exactly why, but by now it should be clear, diets like the "Kendra diet" are rather part of the problem than viable solutions

Implications: Despite the fact that we still don't really understand what's happening, when we are trying to shed the body fat we have acquired in times of gluttony, the few novel insights we have gained from the study at hand should make it even more obvious that "classic" dieting does not hold the answer to the obesity problem. Neither on an individual, nor on a societal level. Instead of "eat less, exercise more", the main message should read: "Don't ever think of dieting, again! Revamp your life, your activity profile and the way you eat and wait for things to fall in place." After all, the "formerly obese kids" in the HF ↔ SC group were not too bad off, when they had returned to a (for rodents!) healthy diet in the 2nd cycle. We may even speculate that the difference the rodents in the control group (SC) would not have been significant anymore, if the scientists had kept the HF ↔ SC rodents on standard chow for another 8 weeks.

The same group is however living (now dead ;-) proof that the notion that you could diet today, look better tomorrow and then return to what has gotten you into misery before is not just illusive, but outright life-threatening. Since caloric restrictions, which are still at the heart of 99% of the mainstream diets, will probably magnify the amplitude (i.e. the up and down) of the yoyo effect and its negative metabolic consequences, it appears reasonable to assume that the yoyo-dieter will eventually be worse off than the "happy fatso" who has been eating whatever he wanted for all his life and dropped dead morbidly obese with a heart attack at 45. After all, it seems likely that he (or she!) will not even live to the 45th year before he falls victim to the very same fate and that after not despite, but rather because of all the temporary austerities... now, this may be like choosing between pest and cholera, and the third option, i.e. following the path of physical culture would alway be my first choice, but honestly, if I had to choose, I'd rather be the fatso who enjoyed his 45 years of pizza, pasta and chocolate pie than the frustrated yoyo dieter.

References

• Barbosa-da-Silva S, Fraulob-Aquino JC, Lopes JR, Mandarim-de-Lacerda CA, Aguila MB. Weight Cycling Enhances Adipose Tissue Inflammatory Responses in Male Mice. PLoS ONE 2012; 7(7): e39837.
• Cinti S, Mitchell G, Barbatelli G, Murano I, Ceresi E. Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res 2005; 46: 2347–2355.
• Hube F, Hauner H. The role of TNF-alpha in human adipose tissue: prevention of weight gain at the expense of insulin resistance? Horm Metab Res. 1999 Dec;31(12):626-31.
• Kim JH, Kim J, Park Y. trans-10,cis-12 Conjugated Linoleic Acid Enhances Endurance Capacity by Increasing Fatty Acid Oxidation and Reducing Glycogen Utilization in Mice. Lipids. 2012 Jul 11.
• Niesler CU, Siddle K, Prins JB. Human preadipocytes display a depot-specific susceptibility to apoptosis. Diabetes. 1998 Aug;47(8):1365-8.  
• Prins JB, Niesler CU, Winterford CM, Bright NA, Siddle K, O'Rahilly S, Walker NI, Cameron DP. Tumor necrosis factor-alpha induces apoptosis of human adipose cells. Diabetes. 1997 Dec;46(12):1939-44.
• Zhu. Ncb5or in Fatty Acid Desaturation and Metabolic Diseases. Zhu Diabetes Research Group. University of Kansas School of Health Professionals. < http://www.alliedhealth.kumc.edu/school/research/zhu/more_info.html > retrieved July 22, 2012