Showing posts with label set point. Show all posts
Showing posts with label set point. Show all posts

Monday, November 11, 2013

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. 2013 --) 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. 2013)
    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. 2013) -- 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. 2013) -- 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 HbA1c (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. 2013), 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. 2013) -- 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. 2013) 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, 2013) -- 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. 2013), 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. 2013)
    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. 2013) -- 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. 2013)
    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. 2013), 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. 2013)
    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. 2013 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. 2013 Nov;15(11):959-67.
  • Kapoor S. Galangin and its emerging anti-neoplastic effects. Cytotechnology. 2013 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. 2013 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. 2013. 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. 2013 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. 2013 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.2013.09.017.

Thursday, August 29, 2013

5% Calorie Restriction & Longterm Dieting Make You Fat and Insulin Resistant. Plus: Model Predicts Weight Loss Based On Number, Weight Lost & Diet Pill Use On Previous Diets

Image 1: "Bikini Body Now!", headlines like this and the unfair suggestion that by following diet X or taking supplement Y you would make it onto the cover of a magazine like that are part of the problem why diets fail, people get discouraged and caught in the diet trap.
The issue of yoyo dieting and the existence and non-existence of a body weight or body fat set-point has been an issue in more than a handful of SuppVersity posts, already (click here to read more). None of the studies I cited (and not even one of those I have read) did yet provide a conclusive and experimentally verifiable answer to the question whether or not there is such a thing as a "set point" and how or even if dieting influences the latter. What common "wisdom" would suggest, though, is that dieting will ruin your metabolism, so that both the post-dieting weight rebound, as well as future problems with losing weight would be programmed.

So the question is: Can you diet yourself fat?

As I have pointed out in previous posts, as well, the hypothesis that you cannot only diet yourself fat, but also make it practically impossible ro reverse the damage is supported by a myriad of N=1 reports on the Internet, objective evidence, on the other hand, is very rare, often inconclusive and mostly either of epidemiological or experimental nature.

In the case of the most recent study from the Pennington Biomedical Research Center at the Louisiana State University, this is yet somewhat different, as it is one of the few studies to combine a controlled dietary intervention with a focus on lifestyle changes that went beyond just telling participants to cut calories (and fats ;-) and a detailed epidemiological analysis of the weight loss history of the subjects to produce a model that would actually allow predictions of future weight loss based on specific aspects of the weightloss history of a given individual.
Figure 1: Based on the diet history and the weight loss success during the 6-month weight loss intervention, the scientists developed a model to predict future weight loss - I would take the exact quantities with a grain of salt, but the qualitative trend, as well as the confounding factors are interesting (data based on Myers. 2013)
As you can see in figure 1, there is something like a "breaking point" at the 10+ diets margin, when it comes to the ability to lose weight. Aside from the fact that you will have all dieters with more than 10 diets packed in there (people could have dieted 100 times or more!), this is by no means evidence for the existence of negative physiological / metabolic side effects of dieting.

In view of another important finding of the study, which is the prognostic validity of previous successful weight loss (figure 1, left) as a positive indicator of future weight loss success, it is much more likely that people who failed 10 or more times, simply make the same mistake(s) over and over again - and while most of them are probably falling victim to one or another of the following culprits
Did you know that a reanalysis of data from the DiOGENES study, a large scale dietary intervention with participants all across Europe, yielded an astonishing result which is yet pretty much in line with the weight loss success of the biggest losers Myers et al. report?

According to Monica H.T. Wong and her colleagues, who scrutinized the weight loss and subsequent weight maintenance of 502 study subjects from 8 different study centers, those participants who lost the most weight during the initial 8-week weight loss phase on a very low calorie diet (800kcal/day) were also the ones who did best in staving the weight off!

Moreover, neither the starting weight nor the glucose sensitivity were significantly associated with the ability to weight and to avoid the dreaded weight rebound, in the course of the 6-months follow up (Wong. 2013). After the weight loss, on the other hand, those participants who lost the most weight also saw the greatest improvements in insulin resistance - ex-post, this could therefore at least be one physiological factor contributing to the long-term success of the biggest losers.
  • following an unbalanced, single-sided / fad diet (e.g. cabbage diet, etc.)
  • starving themselves for X weeks and falling off the wagon, before lasting results can even be achieve
  • cheating too often / not cheating at all
  • overexercising (and undereating)
  • doing no exercise at all
  • meticulously counting  calories and grossing up energy expenditure (as measure with a heart rate monitor and pieces of cake eaten after the workout)
  • eating too little protein to ever be satiated and keep your muscles from being cannibalized 
  • eating too much protein (and no carbs or fats) and running on cortisol and catecholamines until you crach
  • (ab-)using fat burners (esp. stims) and burning out (cf. figure 1, right)
  • seeking for the magic pill, both in supplement and diet form
  • sticking to a diet, because it worked so well for X months, when your body has long changed and the previously optimal diet is now inappropriate for your novel you (e.g. following Atkins diet when you got rid of most of the blubber and turned to physical culture)
an older study by Xi et al. appears to suggest that one item that's not usually on lists like the above could pose a similar, if not even more pronounced thread even to the "educated" dieter.

Being in a very mild caloric deficit, is no solution, but a potential cause of the problem. In fact, "not dieting hard enough" could be just as detrimental, as any of the previously mentioned self-imposed obstacles.

Figure 2: Total and resting energy expenditure of mice that were exposed to a -5% reduction in energy intake for 21 days (graph from Xi. 2010)
This is at least what the results of a study from the Department of Nutrition Sciences at the University of Alabama at Birmingham, Birmingham in Alabama, would suggest.

In 2010, already, Xi et al. have shown that a mild (=5%) reduction in energy intake is probably the worst approach to dieting rodents (and probably humans, as well ;-) can take, as it triggered...
  • increases in fat mass (p < 0.01) 
  • decreases in lean mass (p < 0.01),
  • decreases in total energy expenditure (p < 0.05) and  
  • resting energy expenditure (p < 0.05) 
and all that within no more than 3 weeks and in the absence of reduction in locomotor activity (Xi. 2010) - which means that you cannot exercise these detrimental effects away!

The HIID solution: High Intensity Interval Dieting to get ripped and stay ripped?

You may now certainly complain that biggest losers and mice are nothing you want to go by and you are certainly right; yet still, the notion that slow and steady is not the way to go is also corroborated by results of another 2010 study, this time done in humans and not from Alabama, but from the Washington University School of Medicine, where Fontan et al. conducted an ex-post analysis of the effects of really long-term moderate caloric restriction (and endurance exercise) on insulin-sensitivity and glucose management.

The subjects of the study were 28 volunteers, who had been eating a calorically restricted diet for an average of 6.9 +/- 5.5 years, (mean age 53.0 +/- 11 years), 28 age-, sex-, and body fat-matched endurance runners (EX), and 28 age- and sex-matched sedentary controls eating the SAD or standard Western diet (WD). (Fontana. 2010):
Figure 3:  Parameters of glucose management in 23 subjects who have been following a calorically restricted diet for ~7y  (range 3–20 years; CR) and 28 endurance runners who had been training for an an average of 21 years (range 5–35y; 20 to 90miles/week) relative to 28 sedentary (regular exercise <1 h per week) age and sex matched individuals eating typical Western diets (WD); data calculated based on Fontana. 2010.
Probably much to the surprise to all researchers who love their worms and fruit flies and still believe that starving was the solution to all your problems, Fontana et al. found that long-term caloric restriction in the absence of exercise had statistically highly significant negative consequences on glucose tolerance, as measure in a standardized oral glucose tolerance test (figure 2, small graphs). What's particularly interesting though is that
  1. the non-exercising long-term calorie restricters were practically insulin resistant and still had perfect HOMA-IR values, and that
  2. among long-term dieters there were only 11 subjects (CR-IGT subgroup) who were so glucose intolerant that the result was still statistically significant, though the other 12 subjects' (CR-NGT subgroup) ability to clear the glucose from the bloodstream was in the normal range
Now, while former (1) does tell you much about the validity of HOMA-IR values as a marker of insulin resistance in people on long-term calorie restriction, the latter (2) observation flies right into the face of the "cut your calories to live longer and healthier" paradigm - after all, those 11 calorically restricted subjects had apparently become (or maintained?) glucose intolerant despite having lower BMIs and lower caloric intakes than their peers (1,858 kcal/day, BMI 18.6 vs. 1,729kcal/day, BMI 20 in glucose tolerant caloric restriction subjects, CR-NGT).

Due to the size of the two subgroups in the calorie-restricted group on which Fontana et al. conducted a sub-analysis, we cannot come to any clear-cut conclusions with respect to physical mechanisms that would  explain the general tendency towards a reduced glucose tolerance and the intra-group differences between those who stayed glucose tolerant and those who are now underweight, malnourished and still glucose intolerant:
Dont fall for the false believe that being "normal weight" or even skinny means being healthy! Researchers from the Mayo Clinic in Rochester have found only recently that subjects with normal BMI but central obesity as defined by a high waist-to-hip ratio had the highest cardiovascular death risk and the highest death risk from all causes among the six subgroups (normal weight / overweight / obese x normal waist-to-hip ratio / high waist-to-hip ratio). The risk of cardiovascular death was 2.75 times higher and the risk of death from all causes was 2.08 times higher in normal weight obese people as compared with subjects with normal BMI and normal waist-to-hip ratio. And Dr Lopez-Jimenez points out: "Our research shows that if a person has a normal BMI, this by itself should not reassure them that their risk for heart disease is low. Where their fat is distributed on their body can mean a lot, and that can be determined easily by getting a waist-to-hip measurement, even if their body weight is within normal limits." In lights of the increased fat deposition in the aforementioned rodent study by Xi et al., constant calorie restriction is thus probably not the way to lead a healthy, let alone happy life (ESC. 2013).
"To try to obtain some insight regarding the mechanism responsible for this difference, we did a post hoc evaluation of the data. There were no significant differences between the CR-NGT and CR-IGT groups in either the HOMA-IR (0.32±0.20 versus 0.24±0.10) or the ISI (19.6±7.6 versus 16.8±4.7). Fasting plasma glucose, insulin, and C-peptide concentrations were similarly low in the two CR subgroups. Plasma 30-, 60-, 90-, and 120-min glucose concentrations were significantly higher in the CR-IGT subgroup than in the CR-NGT subgroup. Glucose AUC was significantly higher in the CR-IGT group than in the CR-NGT subgroup. Plasma insulin and C-peptide concentrations after the glucose load were not significantly different between the two CR subgroups except for the 120-min C-peptide value, which was higher in the CR-IGT groups. Insulin AUC and C-peptide AUC were not significantly different between the CR-IGT group and the NGT-CR group." (Fontana. 2010)
If you take closer look at the actual data there are however certain parameters that could at least point into the right directions for future research and provide us with some clues that may help us in setting up our own dietary regimen.

Though not statistically significant (mostly a result of the small size of the dataset for this sub-analysis with N=11 and N=12 subjects in each group), there are a couple of things, it cannot be negated that the insulin tolerant subjects had ...
  • 33% higher IGF-1 + 78% higher testosterone levels,
  • 36% lower fiber intakes + 28% greater VO2MAX
  • 8% higher BMIs
than their insulin resistant peers. Now, you tell me what does "Lower fiber intake, higher IGF-1, higher testosterone, higher BMI" sound like?

Yeah, exactly the nightmare of every physician and exactly what the medical orthodoxy would consider to be indicators of a skewed metabolism and would be trying to solve by putting you on a fiber-laden energy, fat, nutrient and often even protein deficient diet that may work as long as you are morbidly obese and every pound less on the scale takes you one step away from dying from a heart attack but will make you, an already (more or less) lean physically active individual starve yourself into an asexual catabolic state, of which I do not believe and do not even care if it will allow me to live 2 or maybe even 10 years longer...
So what? Conventional wisdom will tell you that the first diet is always the most successful one, that you will regain weight after dieting, no matter what, and that it will become increasingly difficult to get rid of the fat and avoid the yoyo effect.

And in fact, all this will become true, as long as you do your very best to make it become a self-fulfilling prophecy by setting yourself unattainable goals (e.g. "by tomorrow everything will be different") and regarding your "diet" as a temporary step to get from A to B (e.g. "I lost 50 pounds! Hurray, let's party for the rest of the year...")
Implications: Before I get into an essentially pointless rant, let's briefly recapitulate what main, or I should say most relevant outcomes of the individual studies were:
  • Myers' and Wong's studies "proof" only one thing: You got to be prepared to and actually make lifestyle changes! If you do, you will have success, huge success, in fact, in losing and staving off the weight.
  • Xi's and Fontana's studies, as well as the recent results from the Mayo Clinic, on the other hand, underline the fallacy of lifelong dieting. If anything, it is this, i.e. never eating to satiety, always counting calories and disregarding the mandatory nature of exercise, that's underlying reason of "diet resistance" and "diet induced obesity"
None of the studies, however provides significant evidence, let alone "proves", that there was a general physiological response to intentional weight loss that would make subsequent reductions in body weight harder and maintaining your weight (assuming this is not already in the skinny / anorexic zone) near to impossible!
The general message should thus be clear: A "diet" (as in restricted eating) is always just a temporary tool to be used within the broader context of lifestyle changes that are designed to maintain a healthy weight and improve the cardiovascular, and metabolic fitness that is the cornerstone of every goal in the SuppVersity's navigation bar, i.e. staying healthy & improving longevity, boosting performance, building muscle, losing fat and even having a fulfilled sex life... and don't fool yourself and take any of those for granted!

References:
  • Anderson JW, Konz EC, Frederich RC, Wood CL. Long-term weight-loss maintenance: a meta-analysis of US studies. The American Journal of Clinical Nutrition. 2001; 74: 579–584.
  • European Society of Cardiology (ESC). Normal weight individuals with belly fat at highest CVD risk. ScienceDaily. August 27, 2013. < http://www.sciencedaily.com­ /releases/2013/08/120827074153.htm > retrieved August 29, 2013.
  • Fontana L, Klein S, Holloszy JO. Effects of long-term calorie restriction and endurance exercise on glucose tolerance, insulin action, and adipokine production. Age (Dordr). 2010 Mar;32(1):97-108.
  • Li X, Cope MB, Johnson MS, Smith DL Jr, Nagy TR. Mild calorie restriction induces fat accumulation in female C57BL/6J mice. Obesity (Silver Spring). 2010 Mar;18(3):456-62. 
  • Myers VH, McVay MA, Champagne CM, Hollis JF, Coughlin JW, Funk KL, Gullion CM, Jerome GJ, Loria CM, Samuel-Hodge CD, Stevens VJ, Svetkey LP, Brantley PJ. Weight loss history as a predictor of weight loss: results from Phase I of the weight loss maintenance trial. J Behav Med. 2013 Aug 21.
  • Wong MHT, Holst C, Astrup A, Handjieva-Darlenska T, Jebb SA.Caloric Restriction Induces Changes in Insulin and Body Weight Measurements That Are Inversely Associated with Subsequent Weight Regain.PLoS ONE. 2013; 7(8):e42858.