Inulin & Beta Glucan Reduce Body Fat Gain By -50% & -33%! Both Have Similar Effects on the Gut Microbiome, But Only Inulin Appears to Be More Than An Appetite Suppressant

What do these Jerusalem artichokes, agave, bananas, burdock, camas, chicory, coneflower, costus, dandelion, elecampane, garlic,jicama, Leopard's-bane, mugwort, onion, wild yams, yacon and a whole host of other foods have in common? Right! They contain inulin. Whether you will be able to get a whopping amount of 10% inulin in your diet w/out the use of supplements or "enriched" foods, is yet as questionable as how beneficial this actually is for friends of physical culture.

The gut microbiome is not just one of the hottest topics in the (health-)blogosphere, it is also a subject of ongoing research. Research, however, that is, if we are honest, still very much in its infancy. As impressive as the results from the latest studies into the metabolic downstream effects of the administration of fermentable fiber to rodents may be and as obvious as their relation to certain changes in the gut microbiome of the animals may appear - in the end, our understanding of the underlying mechanisms does not allow any reliable prognoses like "double the amount of lactobacilli and you will eventually be able to lose that pouch of body fat you've been carrying around for years now". And yet, if the results from the latest rodent experiments at the Imperial College in London, could be reproduced in humans, I can already foresee that both, the consumption and use of the foods I listed in the caption of the image to the right, as well as related products, extracts and supplements, which contain more or less significant amounts of the naturally occurring polysaccharides, we usually refer to as inulin, will increase in the months and years to come.

Fermentable fiber and the gut-brain-axes: The key to lifelong leanness?

If this is not your first visit to the SuppVersity, you will certainly be aware that the idea of a magic pill (or fiber) that will allow you to eat whatever, whenever and in whichever amounts without having to cope with the metabolic consequences is illusive. When the addition of 10% inulin (or beta glucan) to the diets of 36 male C57BL/6 mice had an "anti-obesogenic" effect, this does not mean that the poor critters who were kept on a hypercaloric high fat (41.8%) diet for 8 weeks did not get obese. What it does mean, though, is that the addition of 10% fermentable (=being food for certain gut bacteria) fiber in the form of

*the producers of these products did not fund or support the study (at least the scientists don't mention that in the respective disclosure ;-)

• inulin from Synergy(TM)*, a fructan based preparation containing both long and short chain
  fructooligosaccharides, or
• beta-glucan from Glucagel(TM)* a highly rich (,80%) barley derived b-glucan preparation

to their otherwise iso-caloric diet (the HFD control contained cellulose) was not without helped to mitigate the negative effects of this diet - a fact the majority of you, of whom I would expect that they are not on a fast-food diet should keep in mind, before they head over to their favorite online supplement vendor and type "Synergy inulin" into the search box.

Figure 1: Effect of addition of 10% fermentable fiber as inulin or beta glucan to the high fat diet of male mice on cumulative weight gain (left), body composition and fatness (middle) and food intake (right) over the course of 8 weeks (data adapted from Arora. 2013)

In spite of that, the results are simply too impressive not to think about their implications in otherwise healthy and even more so previously obese individuals. This is particularly true, because the same microbial changes about which the authors write in a previously published paper from May 2013 that the ...

"[...] increases in both Bifidobacteria and Lactobacillius and a significant increase in short chain fatty acids (SCFA) [went hand in hand with] increase in neuronal activation within the arcuate nucleus (ARC) of animals that received In [inulin] supplementation" (Anastasovska. 2013)

do not (and this is a result of the researchers very latest experiments) simply blunt the rodents appetite. If that was the case, the rodents that received the beta glucan supplemented chow and consumed 12% less energy should have had the most favorable body composition. A cursory glance at figure 1 will yet tell you that this was not the case, though.

Inulin beats beta glucan when it comes to body fat reduction / repression

If we take a closer look a the differential effects of inulin and beta glucan, there yet only one figure that really sticks out and that's the accumulation of fat within the musculature of the animals. The "beautiful marbling" people are looking for in their steaks, however, usually is a harbinger of impeding or even existing skeletal muscle insulin resistance. A muscle fat content above the high fat control (it's certainly a weakness that we don't have a "real" control group on standard rodent chow, here) as Arora et al. observed it in the tissue samples of the beta glucan group, does thus tell you something about its potential usefulness, or rather uselessness of this specific type of fermentable fiber.

Figure 2: Effects of the different types of fermentable fiber on cecal microflora groups (figures are in scientific notation, this means "1E+6" equals 1mio, "1E+9" would be 1 billion etc.; data based on Arora. 2013)

In conjunction with the information about the corresponding changes in the gut microbiome (see figure 2), which appear virtually identical in both groups (specifically the extreme increasesin in both Bifidobacteria (BIF) and Lactobacillius (LAB) really stick out), this does however suggest that the modulatory effect on the composition of the gut flora, or at least the part of it the scientists evaluated in the study at hand, cannot be the only driving force behind the beneficial metabolic effects of inulin.

Inulin or beta glucan? This is not a question... 

While the latter, i.e. inulin, which has by the way been found to directly suppress lipogenesis in a 2011 study by Belgian scientists in a similar HFD rodent model (Dewulf. 2011), appears to be promising for everyone, regardless of whether he or she is poisoning him- or herself with the standard American diet (which is, with its high fat and high carbohydrate content de facto an identical twin of the so-called "high fat diet" in rodent studies), the ingestion of larger amounts of the former, i.e. beta glucan, does at least appear questionable.

If you want to use inulin to your metabolic advantage, you better make sure you get your self a more comfortable place to answer the call of nature - it could call thrice as often! Moreover, large amounts of inulin and other fermentable fiber can induce gastrointestinal distress-

The question is therefore not so much whether it's worth supplementing (it's certainly worth to incorporate some of the initially mentioned foods into your diet, as most of them contain a whole list of other advantageous micronutrients) with inulin or beta glucan - the answer would obviously be inulin - but rather whether it's worth adding larger amounts of inulin to an already healthy diet. And while we cannot answer this question based on the results of the previously cited rodent studies, we could argue that Marwa Zenhom and her colleagues from the Christian Albrecht University in Kiel have already supplied relevant evidence that this would be the case (Zenhom. 2011). After all, the German researchers have been able to show that the PPAR-gamma related anti-inflammatory effects (significant reductions IL-12 secretion in Caco-2 cells and gene expression of IL-12p35, IL-8, and TNFa as well as NF-kB) of oligosaccharides are not (exclusively) brought about by their effects on the gut microbiome, because bacteria simply were not present in their in-vitro study with human Caco-2 cells (cells from the gut lining). Bassaganya-Riera et al. even argue that this effect could be beneficial for IBS patients (Bassaganya-Riera. 2011).

Whether having 10% of your diet in form of inulin, or to make this more conceivable, having 1 tablespoon of plain inulin for every 9 tablespoons of whatever else you eat is either feasible or reasonable, is a whole different story (to put that into perspective: The average inulin intake of Westerners is 1-10g per day (van Loo. 1995). Even 10g would yet only be enough if you ate only 100g of food within 24h!)... and I must forewarn you, if you go by the fecal volume of the mice in the Arora study, it is possible that you will spend >3x more time on the toilette than usual ;-)

References:

• Arora T, Loo RL, Anastasovska J, Gibson GR, Tuohy KM, Sharma RK, Swann JR, Deaville ER, Sleeth ML, Thomas EL, Holmes E, Bell JD, Frost G. Differential effects of two fermentable carbohydrates on central appetite regulation and body composition. PLoS One. 2013;7(8):e43263.
• Anastasovska J, Arora T, Sanchez Canon GJ, Parkinson JR, Touhy K, Gibson GR, Nadkarni NA, So PW, Goldstone AP, Thomas EL, Hankir MK, Van Loo J, Modi N, Bell JD, Frost G. Fermentable carbohydrate alters hypothalamic neuronal activity and protects against the obesogenic environment. Obesity (Silver Spring). 2013 May;20(5):1016-23.
• Astegiano M, Pellicano R, Terzi E, Simondi D, Rizzetto M. Treatment of irritable bowel syndrome. A case control experience. Minerva Gastroenterol Dietol. 2006 Dec;52(4):359-63.
• Bassaganya-Riera J, DiGuardo M, Viladomiu M, de Horna A, Sanchez S, Einerhand AW, Sanders L, Hontecillas R. Soluble fibers and resistant starch ameliorate disease activity in interleukin-10-deficient mice with inflammatory bowel disease. J Nutr. 2011 Jul;141(7):1318-25.
• Dewulf EM, Cani PD, Neyrinck AM, Possemiers S, Van Holle A, Muccioli GG, Deldicque L, Bindels LB, Pachikian BD, Sohet FM, Mignolet E, Francaux M, Larondelle Y, Delzenne NM. Inulin-type fructans with prebiotic properties counteract GPR43 overexpression and PPARγ-related adipogenesis in the white adipose tissue of high-fat diet-fed mice. J Nutr Biochem. 2011 Aug;22(8):712-22.  
• van Loo J, Coussement P, de Leenheer L, Hoebregs H, Smits G. On the presence of inulin and oligofructose as natural ingredients in the western diet. Crit Rev Food Sci Nutr. 1995 Nov;35(6):525-52.
• Zenhom M, Hyder A, de Vrese M, Heller KJ, Roeder T, Schrezenmeir J. Prebiotic oligosaccharides reduce proinflammatory cytokines in intestinal Caco-2 cells via activation of PPARγ and peptidoglycan recognition protein 3. J Nutr. 2011 May;141(5):971-7.

Leucine + Resveratrol - Synergistic Sirtuin Boosters: +118% Fatty Acid Oxidation, 60% Increase In Muscular Glucose Uptake, -30% Visceral Fat & More - To Good to be True?

Image 1: Can you really team up leucine (or HMB) and resveratrol to make tired mitochondria get a move on? NuSirt Sciences says "YES!" And in the dish and rodents it's actually already working.

What happens if you marry a well-known AMPK promoter and exercise mimetic, with an even more prominent exercise adjuvant and nutritional mTOR booster? Will they neutralize each other? Think about it.... ok, now gimme your answer: What happens if you put resveratrol and leucine together? At first it does not really make sense, does it? Right, it doesn't, at least not unless you follow the same train of thought, the researchers from NuSirt Sciences. NuSirt? That rings a bell, hah? Yeah those were the guys who did a study on their 250mg leucine + 30mg vitamin B6 proprietary blend NuFit (see "Testosterone - 12% Drop /W 75g Glucose? Fat Loss - Adzuki, Leucine + B6 or HiMaize & More") and actually, the leucine + resveratrol combination is sort of a spin-off of this initial research.

If you put Sirt1 & Sirt1 together, it suddenly makes sense!

In their latest study (and you bet a future product!) Bruckbauer et al. build on their previous research on the agonistic effects HMB, alpha-KIC or leucine have on skeletal muscle Sirt-1 activity (Bruckbauer. 2011) and rationalize that it seems legit to combine one Sirtuin portein promoter with another one in order to achieve an even more pronounced effect - makes sense, right? Resveratrol the proven AMPK-promoter and igniter of the longevity, gene transcription, cell survival and apoptosis regulating Sir2 proteins (=sirtuins) and leucine the mTOR promoting and, as of late, proven Sirt1 agonist, they could actually form a synergistic duo for fat oxidation, glucose management, the reduction of oxidative stress and inflammation and even longevity!

Figure 1: Effects on sirtuin & AMPK expression in muscle and fat cells upon incubation with leucine, HMB and resveratrol and the respective combinations (left) and effects fatty acid oxidation in isolated rat skeletal muscle upon incubation in low and high glucose conditions (data based on Bruckbauer. 2013)

Now, aside from Sirt1, which is mainly expressed in the nucleus of a cell, another one of the Sir2 proteins, Sirt3, which is expressed predominantly in the mitochondria has as of late gathered quite some attention, as mitochondrial dys- or malfunction is one, if not the common denominator of many of the pathological features of the metabolic and neuro-endocrine ailments the Western diabesity society is suffering from: insulin resistance, type II diabetes, Alzheimer's , you name them! No wonder the NuSirt guys (and girls) are striving to find a marketable way to set them both in full gear and if you take a closer look at the data in figure 1 their initially counter-intuitive approach to bath muscle and fat cells in resveratrol  + HMB / leucine solutions yields impressive results:

• resveratrol, leucine and HMB, alone, exerted only weak independent effects on Sirt1, Sirt 3 and AMPK
• resveratrol and leucine or HMB, combined, yielded Sirt1 and Sirt3 activity increases in the ~50% range (p < 0.05) and AMPK increases of +42% and +55% (p < 0.03); particularly noteworthy are the ~125-175% increases (p < 0.02) muscle cells (remember: Sirt3 is expressed in the mitochondria!)
• the ensuing increases in fatty acid oxidation in incubated muscle cells reached statistical significance in the presence of low (5 mM) glucose levels, only, when and 5 µM HMB or  0.5 mM leucine were co-incubated with 200 nM (~18%; p < 0.05), in the high glucose condition, however, all treatments broad about significant increases in fatty acid oxidation, of which those in the leucine- and HMB-resveratrol combination treatments were the most pronounced (118% and 91% stimulation, respectively; p < 0.005)

Especially the last finding, i.e. the increase in fatty acid oxidation in an in-vitro condition that resembles the hyperglycemic state the average type II diabetic who is not popping tons of metformin and/or injecting insulin is constantly in, makes these results particularly interesting, as it appears as if a "non-pharmacological" (what by the way is "pharmacological" and what isn't?) solution to the diabesity problem could already be hidden on the shelves of your GNC right next door (I assume they carry leucine and resveratrol products ;-)!

Outside of the box... ahh, I mean, ... the petri dish!

In view of the fact that 75% of the in-vitro high performers suck in the rodent model already and of those another 75% don't work in human trials you will be pleased to hear that NuScirt Sciences' resveratrol + leucine / HMB combination has already overcome the first of these hurdles: At least in DIO (diet-induced-obese) rodents who on a 6-week high fat diet regimen, the combination works.

Figure 2: Weight gain, visceral adipose volume, PET measured palmitate uptake, respiratory rate (lower levels = higher relative fat oxidation), heat production relative to body weight, food intake; all value expressed relative to DIO mice who were maintained on an unsupplemented control diet (data based on Bruckbauer. 2013)

Now, it's not as if the rodents would have made it to the Mr Olympia stage, but if you take a closer look at the pattern that's emerging here, it's quite clear that the sirtuin booster does its job in this rodent model. Aside from its ameliorative effect on weight gain, the combination of resveratrol and leucine, led to statistically significant improvements in glucose management and improvements in inflammatory markers (including the anti-inflammatory adipokine adiponectin, see figure 2).

Figure 2: Glucose, insulin and HOMA IR levels, muscular glucose uptake (left), C-reactive protein , IL-6, MCP-1 and adiponectin (right) ; all value expressed relative to DIO mice who were maintained on an unsupplemented control diet (data based on Bruckbauer. 2013)

Most importantly, however it effectively cut through the exuberant amount of visceral adipose tissue (>30% reduction), ramped up the palmitate (fatty acid) uptake, oxidation and heat production (=thermogenesis). Despite all these metabolic improvements which took place in the absence of a simple reduction in food intake, there are still a couple of things left to be desired:

What are the human equivalent doses, here? Since I know you would be asking I did the math for you and you will be pleasantly surprised (HED for 80kg humans)

• 12.5mg resv. = 9mg
• 225mg resv. = 136mg
• 2g HMB = 1.1-1.4g
• 10g HMB = 7.2g
• 24g leucine = 14.3g

I am well aware that it must look as if I had the typical poor arithmetic abilities of the average physicist who has totally forgotten how to calculate using figures instead of letters, but the reason for the discrepancies is that I calculated the exact HEDs based on body weight and food intake for each of the groups.

1. Supplementation with the respective human equivalent doses should yield the same astonishing results in humans as it did in the diet-induced obese mice.
2. The protocol should have effects not just in morbidly obese diabetic human beings, but also in overweight and ideally even lean individuals.
3. The supp must work if you don't put it into the chow, but pop it in separate doses (e.g. 3x/day) as a capsule or tablet.

The good news however is that if 1-3 apply, you could start benefiting from this "super supplement" right now! After all, the resveratrol dose of 12.5mg per kilogram of chow (the mice in the study did not consume more than max. 4g(!) per day) is so low that the 10g package I just saw for 20$ over at the webshop of a major bulk supplier would last you literally forever ...

Unfortunately, this is exactly why I don't believe that LeuResSirt, or whatever other stupid name the final product will be given, is going to work - I mean, come on, you can't tell me that there are not already people out there who get 15-20g of leucine everyday and pop resveratrol in 100x the necessary dose of 8-9mg everyday!? And did they turn into a beast, become fast-food resistant or lose fat magically? What? Yeah... that must be Phil Heath secret, right... how come I did not realize that before? ;-)

Bottom line: Regardless of the probably justified skepticism, I will still keep you posted on whether or not NuSirt knocks out another incredible (in the literal sense) human study like the one on NuFit (see "Testosterone - 12% Drop /W 75g Glucose? Fat Loss - Adzuki, Leucine + B6 or HiMaize & More"). So stay tuned, you all know that no supplement will ever more ergogenic than your daily dose of SuppVersity news!

References:

• Bruckbauer A, Zemel MB. Effects of dairy consumption on SIRT1 and mitochondrial biogenesis in adipocytes and muscle cells. Nutr Metab (Lond). 2011 Dec 20;8:91.
• Bruckbauer A, Zemel MB, Thorpe T, Akula MR, Stuckey AC, Osborne D, Martin EB, Kennel S, Wall JS. Synergistic effects of leucine and resveratrol on insulin sensitivity and fat metabolism in adipocytes and mice. Nutr Metab (Lond). 2013 Aug 22;9(1):77.

Saturated Fat Kills Gut Bacteria & Modifies Genes in the Distal Small Intestine - Another Reason Why We Get Fat? Plus: Bacteria, Fiber, SCFA, GLP-1 & PYY Revisited

Image 1: Bacteria, there are >100 trillion of them right inside of your digestive track, you can hardly know them all and scientists do neither - the only thing we are beginning to understand, though, is that it may be a good idea to get them to know at least somewhat better ;-)

I guess some of you have already noticed that I was (and probably am now, again) somewhat behind, as far as answering your questions, comments an wise remarks are concerned. Actually it is still more of a coincidence that today's SuppVersity news, which, as you see is not an Adelfo Cerame post (don't forget to keep the fingers crossed for him! This is his weekend!), could actually be interpreted as my somewhat lengthy response to a comment from Vincente on the effects of GLP-1 on chocolate preference in rats and an interesting hypothesis of his, on how this could all relate to my previous post on the fat burning effects of GLP-1 ("Eat More, Burn More and Lose Fat Like on Crack with GLP-1!?"). What, that was Vincente's reasoning, what, if those obese individuals had just messed up their gut bacteria an would lack those beneficial bacteria, which convert the fiber and resistant starch that makes it through your small intestine, right down into your long one to short chain fatty acids?

Does obesity come from within?

I guess by now some of you may already be asking themselves, where all that relates to GLP-1 and eating more, burning more and losing fat like on crack. Well, the missing link if you will is actually not a link, but rather a receptor - the free fatty acid receptor, FFR, which "sniffs" the presence of the short chain fatty acids and triggers the release of GLP-1 and PYY. Those two incretin hormones, of which researchers have found within the past 10 years or so that they are way more than mere "satiety signals. Several research studies in rodents have shown that the anti-obesogenic effects of GLP-1 and PYY are if at all, only partly mediated by reductions in food intake, yet mostly via complex downstream effects on total energy expenditure, glucose and fatty acid oxidation.

Contrary to exogenously administered GLP-1, which is actually being used in the treatment of diabetes an the metabolic syndrome, the in-vivo data from rodent studies, which suggests that high fiber diets protects those little critters from diet induced obesity (Aziz. 2008; Shen. 2008; Zhou. 2008) have, as Robertson et al. pointed out only recently, not yet been confirmed in humans trials (Robertson. 2013). Moreover, the latest results from the Merck Reserach Lab show, contrary to previous evidence from the Cambridge Institute for Medical Research (Tolhorst. 2013), that even our current assumption with respect to the underlying mechanism, could at least be incomplete (Lin. 2013). This does not mean that the short chain fatty acids would not produce the desired increase in GLP-1 nad PYY, but rather that their effects are not solely mediated by  the aforementioned free fatty acid receptor in the gut.

Let's make things even more complicated and bring some long chain fatty acids to the table!

What is yet self-evident though is that the way GLP-1 and PYY modulate energy utilization punches yet another huge hole in the prostrated "calories in vs. calories out hypothesis", one that has little to nothing to o with insulin and one that acquires yet another shade of gray, when we look at the long-chain counterpart of the "bacterial excrements" the dreaded or beloved (depending on the standpoint of the individual) saturated fatty acids (SFA) and a recently published study by scientists from the Wageningen University in the Netherlands (De Wit. 2013), who investigated the long-term effects (8 week, study conducted on mice) of high fat diets with fats from different fat sources

• palm oil - representing the saturated fatty acids,
• olive oil - representing the mono-unsaturated fatty acids, and
• safflower oil - representing the polyunsaturated fatty acids

on body weight gain, liver triglycerides and the whole other standard parameters and their relation changes in the gut microbiome and the amount of fat that "left" the animals undigested.

Figure 1: Fecal fat and energy loss, total energy intake and relative (to control on normal chow) liver triglycerides, oral glucose tolerance and weight gain over the 8 week study period (de Wit. 2013)

A casual look at the data in figure 1 should suffice to see that there is a profound mismatch between almost all classic features of the metabolic syndrome of which we would usually expect that they would be closely associated:

• the rodents in the palm oil group ate the least amount of energy, excreted the greatest amount of fat and total energy in their feces and still gained the greatest amount of body weight and had the highest amount of liver triglycerides (beginning non-alcoholic fatty liver disease)
• the rodents in the olive oil group did not consume significantly more amount of energy or excrete significantly more amount of fat / energy in their feces and still gained ~40% less body weight and did not exhibit similarly high triglyceride storage in the liver as the rodents on the saturate fat (palm oil)
• the rodents in the safflower oil group were comparably ravenous (+20% energy intake), but although they did not excrete more energy and fat than their peers, their bosy weight gain was profoundly reduced and their liver triglycerides were better than in the "non high fat control group" and yet their glucose tolerance was not the best, but the worst of all the three groups

All that does only make sense, when a second parameter, or I should say another 100 trillion bacterial parameters come into play and the SFA induced reduction in microbial diversity and
composition (increased the firmicutes/bacteroidetes ratio) are accounted for, as well. those, this is at least what de Wit et al. believe are namely responsible for the complex changes in genes that regulate the fatty acid metabolism and expression of inflammatory markers, the scientists observed

Chicken or egg, cause of correlation? Or just gut optimization?

Even tde Wit et al. do yet point out that their observations do not provide significant evidence to establish a causal relationship between the bacterial changes, which are a direct result of an overflow of (selectively) antimicrobial saturated fats into the distal part of the intestine, the subsequent disturbances in the bacterial balance and (human!) gene expression in the gut and the  particularly pronounced obesogenic effects of saturated fatty acids.

You could, at least in my humble opinion, even argue that these are simply adaptive effects that ensure that the "host", in this case the rodents, "gets the most" out of his diet - after all, this is exactly what we are seeing here: A modulation of genes related to the conservation and storage of energy, such as the downregulation of the Bcmo 1 gene that predisposes to the development of obesity and non-alcoholic fatty liver disease (Hessel. 2008),  which allows for maximal energy efficiency despite greater fecal energy loss.

Conclusion? Drink safflower oil?

That these results should not be taken as an incentive to guzzle safflower oil (or drop your coconut oil for the latter) should be obvious. Just as obvious, by the way, as the realization that despite all the hoopla and my own excitement about the newly discovered importance of the gut microbiome as one of the possible contributers to the global obesity epidemic. We are understanding way too little about its interactions with its host, i.e. us, to exclude that we are not - yet again - confusing cause and effect, causation and correlation and take our gut microbiome, which is eventually nothing else than a mirror of our healthy or unhealthy lifestyle for the real deal, and try to modulate and fix the mirror image with anti-, pro- or prebiotics without working on what stands right before the mirror: The sedentary, convenience food consumer, who works to jobs and rather watches TV till late at night instead of getting his 7-8h of sleep....

References:

1. Aziz AA, Kenney LS, Goulet B, Abdel-Aal el-S. Dietary starch type affects body weight and glycemic control in freely fed but not energy-restricted obese rats. J Nutr. 2009 Oct;139(10):1881-9. Epub 2009 Aug 19. 
2. Hessel S, Eichinger A, Isken A, Amengual J, Hunzelmann S, Hoeller U, Elste V,  Hunziker W, Goralczyk R, Oberhauser V, von Lintig J, Wyss A. CMO1 deficiency abolishes vitamin A production from beta-carotene and alters lipid metabolism in mice. J Biol Chem. 2007 Nov 16;282(46):33553-61.
3. Lin HV, Frassetto A, Kowalik EJ Jr, Nawrocki AR, Lu MM, Kosinski JR, Hubert JA, Szeto D, Yao X, Forrest G, Marsh DJ. Butyrate and propionate protect against  diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms. PLoS One. 2013;7(4):e35240.
4. Robertson MD. Dietary-resistant starch and glucose metabolism. Curr Opin Clin Nutr Metab Care. 2013 Jul;15(4):362-7. 
5. Shen L, Keenan MJ, Martin RJ, Tulley RT, Raggio AM, McCutcheon KL, Zhou J. Dietary resistant starch increases hypothalamic POMC expression in rats. Obesity  (Silver Spring). 2009 Jan;17(1):40-5. Epub 2008 Oct 23.
6. Tolhurst G, Heffron H, Lam YS, Parker HE, Habib AM, Diakogiannaki E, Cameron J, Grosse J, Reimann F, Gribble FM. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes. 2013 Feb;61(2):364-71.
7. Zhou J, Martin RJ, Tulley RT, Raggio AM, McCutcheon KL, Shen L, Danna SC, Tripathy S, Hegsted M, Keenan MJ. Dietary resistant starch upregulates total GLP-1 and PYY in a sustained day-long manner through fermentation in rodents. Am J Physiol Endocrinol Metab. 2008 Nov;295(5):E1160-6.
8. de Wit NJ, Derrien M, Bosch-Vermeulen H, Oosterink E, Keshtkar S, Duval C, de Vogel-van den Bosch J, Kleerebezem M, Müller M, van der Meer R. Saturated fat stimulates obesity and hepatic steatosis and affects gut microbiota composition by an enhanced overflow of dietary fat to the distal intestine. Am J Physiol Gastrointest Liver Physiol. 2013 Jun 14.
9. Zhou J, Martin RJ, Tulley RT, Raggio AM, McCutcheon KL, Shen L, Danna SC, Tripathy S, Hegsted M, Keenan MJ. Dietary resistant starch upregulates total GLP-1 and PYY in a sustained day-long manner through fermentation in rodents. Am J Physiol Endocrinol Metab. 2008 Nov;295(5):E1160-6.