SCFA's inhibit insulin signalling in fat cells

I havent seen this study reported anywhere else in the blogosphere!

The gut microbiota suppresses insulin-mediated fat accumulation via the short-chain fatty acid receptor GPR43.

 Hence, this report also supports our results that suppression of adipose insulin signalling by GPR43 activation leads to prevention of obesity and improves systemic insulin sensitivity.

Look at how blasphemous this statement is, suppression of insulin signalling in adipose tissue prevents obesity.    lol  whha  ??!?!?!?!?!!!!?

Anyway, to cut a long story short, GPR43 is a receptor for short-chain fatty acids including acetate, and is expressed in various tissues including the adipocyte. There was some controversy surrounding the function of GPR43 in adipocytes because in vitro studies had shown that it promoted adipogenesis, but this research group claims to have shown that the in vitro observations of GPR43 do not match those of in vivo.

This study seems to support the nutrient partitioning idea, as GPR43 not only suppresses insulin signalling in adipocytes but improves systemic insulin signalling including in the muscle.

One observation I would like to make however, is that I have tried on numerous occasions high dose inulin for several days/weeks at a time but did not notice a reduction in fat mass.

sigh..............

More on Fat Cell dynamics, - in response to weight loss/calorie restriction

cba today so ima just copy/paste

Adaptation of human adipose tissue to hypocaloric diet

• In a study on type 2 diabetes patients submitted to 1-year dietary intervention combined with exercise, the authors stratified the adipocytes into four subfractions in respect to the cell size.16 At the end of intervention, the adipocyte size was reduced just in subfraction of ‘large’ adipocytes, while the other three remained unchanged.
• investigations suggest that individuals with hypertrophic obesity—who are at higher metabolic risk6, 18, 19, 20—are more responsive to the adipocyte size-reducing effect of hypocaloric diets in comparison with those with small adipocytes, that is, with hyperplasic obesity.
• In another study, using electron microscopy, the response was variable in a group of six patients submitted to 6 weeks’ LCD: in subjects with higher proportion of large adipocytes (hypertrophic obesity), the authors observed a shift from the fraction of large adipocytes towards the small ones, whereas in subjects with higher proportion of small adipocytes (hyperplasic obesity) no shift between the fractions occurred.
• no reduction of adipocyte size in abdominal (but not in gluteal) SCAT was found after 20 weeks’ LCD in one study.15

Lipogenesis

• insulin stimulation of de novo lipogenesis measured on isolated SCAT adipocytes was blunted after 4-weeks’ VLCD.10 However, in weight-maintenance phase, 1–3 years after initiation of the weight reducing program or after gastric banding, both, the basal- and insulin-stimulated, de novo lipogenesis measured on isolated adipocytes were increased when compared with the pre-diet condition.31

Prospective and controlled studies of the actions of insulin and catecholamine in fat cells of obese women following weight reduction.

• Many of the adipocyte abnormalities associated with obesity improve after weight loss [12–15]. Fat cell size decreases, as does basal lipolysis. Insulin and catecholamine actions are improved. However, it is not known if these actions completely return to normal. A full normalisation would suggest that the abnormalities are secondary to obesity. However, incomplete normalisation would suggest primary defects in adipocyte function that cannot be cured by weight loss
• A prominent finding in this study was a decrease in fat cell volume below the control level in weight-reduced obese subjects. Since BMI, fat distribution and body fat content were similar in obese subjects and their controls, the results imply that adipose hyperplasia (at least in abdominal subcutaneous adipose tissue) is a major feature of weight-reduced obese subjects
• This further strengthens the idea that insulin resistance is secondary to obesity, whereas adipose hypercellularity and low adipose lipolytic rates may be primary factors in obesity.
• In conclusion, adipose tissue hyperplasia (many small fat cells) is present in the weight-reduced state and probably explains the low rates of adipocyte lipolysis in this condition. However, adipocyte insulin resistance is a secondary and fully reversible phenomenon in obesity.

You cant select a random obese person from the population then tell him "fat mass is only about CICO", because you have no idea of the amount of fat cell hyperplasia they are suffering from. The more fat cells you have, the fatter youll be, BY DEFAULT.

Why am I posting this? Because I want it to be apparent that people suffering from significant hyperplasia will be unable to resolve their dysfunctional metabolism with diet and exercise alone, despite what you may hear from high standing medical doctors and bloggers. More likely we will need pharmaceutical intervention or in the worst case scenario, surgery.

How can you tell if your suffering from hyperplasia? Well, while I dont have references to back up these claims, I have several ideas. Firstly, the ease with which you rebound weight gain after weight loss will signify hyperplasia. Also the degree to which you are metabolically healthy despite significant increases in weight will signify significant hyperplasia. If you was very heavy but with no clear signs of diabetes = significant hyperplasia.

Also, just look at your fat tissue, is it very "lumpy" with lots of partitions? or is it very roundish and circular? The former = hyperplasia. See pictures in this post for example. The guy in the left most likely has significantly more hyperplasia than the right.

The dissonance of obesity

I was prompted to write this post after watching a guest video by David Pizzaro on the topic of "disgust".

He describes the emotion of disgust as a universal response, i.e. it is similarly present throughout many different culture's, and so this is good evidence that it is hardwired into our biology.

"people seem to have a natural aversion response to things that are gross, i.e. things that might contaminate us or give us diseases"

Obviously the emotion disgust has survival benefits, by making us avoid things which "disgust" us decreases our likelihood of infection. A key point here is "avoidance". Usually, "avoidance" is the primary action we take when our emotion of disgust is invoked. But there are ofcourse other actions we might take depending on how it directly affects us.

For example, imagine you wake up one morning and find a pile of dog shit right in the middle of your doorstep. What action will you take? Now ofcourse, upon first contact, your very likely to experience the emotion of disgust and your natural instinct will be to "avoid" the poop. But there is a problem, it affects you because its on YOUR doorstep. Avoiding it forever is not a viable option. So instead, you will most likely, reluctantly,  clean it up, using plastic gloves ( avoidance again ).

But now lets say one morning you wake up and find a pile of dog shit on your neighbor's doorstep. What action will you take here? It will ofcourse be complete avoidance, you certainly wouldn't clean it up for your neighbor would you? Since its not on your doorstep, it doesnt directly affect you, and so complete avoidance is likely to be the ONLY action you will take.

Anyway, cut to the chase, something which I have long noticed, and cant seem to shake, is that fat people, especially morbidly obese people, seem to invoke the disgust reflex. I cant speak for others, but when I see the severely obese people, I am revolted. This is despite every logical and rational thought telling me that these people are essentially, victims.

When I see a severely obese person in the street the first thought that comes to mind is "how could you let yourself get like that, its gross" But this is not me thinking, its not my conscious logical rational mind coming up with this, but rather this thought is coming deep from the hindbrain.

The question is, why ? WHY does obesity invoke the disgust reflex? Well, if we go back to the definition etc, we know the disgust emotion has been designed to make us avoid things that could contaminate us, infect us, or things that are likely to be diseased. In this light, it seems as if the body instinctively regards the state of obesity as one of disease. We all know that obesity reduces sexual attractiveness, being disgusted by obese people could be one way our biology protects us from mating with potentially poor gene's. 

As an example, physicians are less likely to 'Bond' with overweight patients. Why is that? Does the state of obesity in the patients subconsciously invoke the disgust reflex and subtly guide the physicians to action "avoidance" with them?

'Most' of us who has studied the subject of obesity intensely know all too well the truth. I.E. that obesity is a disease. Something about the adipose tissue has malfunctioned. The dissonance part is what I find interesting.  I.E. the dissonance between our bodies instinctively regarding obesity as a disease and the idea that "over-feeding" causes obesity.

The dissonance is that I believe that these 2 points ( i.e. obesity being a disease and simultaneously being caused by over-eating ) are evolutionary incompatible.

In an uncertain, unpredictable, and aggressive world, it should be advantageous to have access to a large of amount of calories. Having a consistent and bulky supply of nutritious food would surely be of benefit to those organisms who can access it. You might even expect this advantage to propagate and advertise itself through the organism by having the organism display a physically and sexually appealing phenotype. Afterall, we all know that emaciation is a massive sexual turn off.

And the more, the better, right? I.E. The greater the quantity of nutritious food we have access to, the more likely it is that we should survive in a harsh world. Right ? And we should advertise that increased chance of survival through consumption of that food which will gives us a physically pleasing phenotype.

But here's the paradox, because apparently, taking advantage of that large cache of food and consuming it leads ( allegedly ) to the state known as obesity, which accordingly, decreases our chance of reproduction through reduced sexual appeal, aswell as ( again, allegedly ) predisposing us to a whole host of other ailments that reduce our chance of survival.

If you believe that over-eating causes obesity, then essentially what your saying is that,  paradoxically, having access to and taking advantage of large caches of food which would normally increase an organisms survival, actually leads to a state that reduces survival and chance of gene propagation.

Having access to something which normally increases your survival, actually, decreases your survival if that something ( food ) is overindulged in.

Does that make sense?

Remember that our biology regards the state of obesity as a disease. So its almost like saying your body regards the state of having access to large quantities of food as a disease.

hhhhhhmmmmmmmm.

calorie counting is just dumb

The more I think about the idea of CICO the more I realize just how full retard it is. I mean, firstly, lets say you decide to cut your calorie intake to 1200 per day. Have you even thought about what it is exactly that your trying to achieve by doing this? You have NO IDEA what your energy expenditure is, and even if you did, the act of changing your calorie intake will change that expenditure.

This is exactly like a dog chasing its own tail going round in circles, because while your busy trying to lower your calories to decrease fat stores, your body is constantly monitoring your energy intake and adjusting your energy expenditure to match that energy intake so that fat stores are preserved and held constant.

The very moment you start consciously cutting calories, you become the dog chasing its own tail. Your chasing something which is in turn chasing you back.  Your trying to create a large gap between energy in and energy out, meanwhile your body is constantly trying to close that same gap,

Referring back to the Myths/presumptions paper on obesity, we can quite easily see why Myth #1 is false.....

Myth number 1: Small sustained changes in energy intake or expenditure will produce large, long-term weight changes.

This notion that if you over-eat 10 calories per day youll gain 1lb of fat in 350 days is completely backwards logic and putting the cart before the horse. The faulty logic is that "we need to regulate our energy intake to match our energy expenditure" to be weight stable. This is NOT how it works. This is backwards. Whats REALLY happening is that energy expenditure is constantly being tweaked to match energy intake. Its not that we have to fine tune our energy intake to match our energy expenditure over the long term to remain weight stable.

Instead, our energy expenditure is constantly being fine tuned to match energy intake over the longterm. THATS why normal lean people remain weight stable despite wild fluctuations in energy intake.

The reason it works this way is simple. Energy availability from the environment is unpredictable. The organisms body cannot force the organism to intake a certain amount of calories per day because that calorie availability is completely unknown and uncertain. Instead biology has evolved to manipulate its energy expenditure based on the energy intake the organism can achieve in that day.

To correct myth 1, it should be re-stated as....

Changes in energy expenditure will occur in response to changes in energy intake such that over the long-term energy expenditure will match energy intake..

All the evidence I have seen indicates that fat stores are the most protected commodity in the body. Long term starvation usually results in death from organ failure due to loss of lean mass, Death from starvation never results from fat mass reaching zero. I.E. , you never run out of calories. Your body values its fat stores more than the lean mass. But we also have to remember that lean mass loss in starvation is because your body is reducing energy output, like a crew on a sinking ship thats throwing stuff over-board so as to reduce its weight and keep it afloat, your body throws out stuff that contributes to energy expenditure.

I enjoyed the latest spark form Gary Taubes,  he makes the same point that many of us have been throwing around for yonks, i.e. that the overeating causes obesity type of thinking is circular logic.

Why do we get fat? Because we overeat.
How do we know we’re overeating? Because we’re getting fatter.
And why are we getting fatter? Because we’re overeating.
And so it goes, round and round.

I have argued previously that even the concept and word "overeating" is all but impossible to define. At no point can you feed someone amount of calories X and then confidently say whether or not you have "overfed" them.    This is because, the current way "overfed" is defined  is if you feed someone X amount of calories and that they gain weight from it. But it is (nigh) impossible to predict how much weight someone will gain from feeding them X calories.

Lets say I take a random person off the street, and feed them 5000 calories for the day. But thats the ONLY information I give you. How are you gonna predict if and how much weight they will gain? You cant, because I havent told you anything about the persons genetic and/or metabolic status, nor have I told you what im feeding them with. I could be feeding them with 5000 calories of doughnuts or 5000 calories of fatty meat and vegetables. Simply focusing on caloric intake alone gets you NOWHERE.

Slept well last night

Took 9mg melatonin last night about 2hrs before bed, felt drowsy within about 30 minutes then couldn't stay awake at 2hr mark. Had good deep sleep. I have noticed that I feel most refreshed when I get quality REM sleep, that is, that period near the end of sleep where your half-awake, half asleep, and also dreaming. If this final phase of sleep goes well, I just feel amazing, I get up feeling full of energy and brain works exceptionally well.

Felt a bit groggy in the morning which I know was due to the melatonin dose, but it wore off within 2 hrs. I had to take the melatonin because the Cabergoline was giving me insomnia. 2 things I have noticed about Cabergoline is that, I get severe anxiety on it, but also libido is massively increased!

Im struggling a bit with this blog at the moment, its getting harder and harder to find stuff to blog on because there are TONS of health/nutrition blogs out there. Competition for novel information is fierce. Although im not trying to turn this blog into some public guru know it all website. This place is for me to document my personal thoughts/theories aswell as information that I find valuable. Dont get me wrong, I appreciate feedback ALOT, but I want to avoid falling into the mindset of blogging to appease an audience, but instead I want to blog for myself. Then again, I dont want to blog on things that others have blogged on elsewhere, and so this further makes new content very difficult to come up with, also my occupation is not the field of nutrition/medicine so im not "in the loop".


I want to throw up some info from Dan's video here.....


22:00 minute mark

• How do we avoid making the same mistakes over and over and over again?

The idea is, that we have a natural way of looking at the information that comes at us. And when we rely on this natural way of looking at this information, there's a good chance we'll get it wrong, because our natural ways of dealing with the information can be biased. However, the question is can we get over these natural tendencies and under what conditions can we?

This reminds of the problem in Metabolic Syndrome and biased obesity research. Basically  alot of health issues are "mistakenly" attributed to as being "caused" by obesity, and I think this is happening because of how we are being fed information. Humans are massively biased towards visual information, seeing is believing.  For example, when we see an obese person, we automatically attribute all health problems that person has to their weight, because the weight is the thing we "see" has changed so dramatically from a healthy normal lean person. 

We dont "see" all the little things going on inside an obese person with metabolic syndrome, like hepatic IR, insulin hyper-secretion  + all the other biochemical changes going on. In this case it is thus very easy to fall into the trap of thinking that obesity "causes" all these health problems because the increase in bodyweight is so glaringly obvious meanwhile the biochemical changes are massively obscure and difficult to measure. 

31:00

• Should we trust our intuitions?

Our intuitions are often wrong, but also, we often dont recognize our faults. The only way to get reliable information to get the correct answer to a problem is through experimentation, measurement etc. If you want the right answer, it is best to remove all human intuition, remove all human judgement, and bias, and just follow the dots. 

For example the other day I was texting a lady friend, and I didnt get a reply. My intuition was to think, she was ignoring me, she didnt like me. Or something. Turns out that she was replying to my texts, but they got stuck in the network, and several days later I got her texts all together simultaneously ( the delayed text problem ). My intuition was wrong you see, she was not ignoring me, it was a stupid mobile phone network error that was the issue. 

I want to take this opportunity to link to another example of this. This little post by Armstrong is so true. Peoples "intuition" was wrong about 

Chernobyl. 

You have to just follow the breadcrumbs and stop trying to further theories that support what someone wants to happen. 

Also in 31:00 segment of the video Dan also talks about the best way to learn, ( which can also be ascribed to "the best way to get the right answer" )  The best way is to try lots of times, with changing different variables, and to have immediate feedback, and for that feedback to be precise.

This is a good explanation for why obesity research is a mess, and why figuring out sleep is difficult. Lots of variables, some randomness due to genetics etc. 

43:22

• Can we avoid emotional interference's in our daily decision making?

Emotions are designed to take over cognition, override "free will" in a sense. Dan says emotions are designed to aggressively take over and execute a specific sequence of events. But most importantly, he says emotions are "hard to fight"

Infact Dan then argues that trying to fight your emotions is kind of pointless. The best you can do is instead modify your situation so that you will not be put in a place where those emotions are invoked and so you do not have to fight them.

I think this bears significance for LC and dieting. If you want to avoid falling off the LC bandwagon, the best you can do is avoid situations where carby food is going to be available. I notice people often report succumbing to carbs during holidays. In these situations I dont think you should blame yourself.  

Powdered food ( carbs? ) appears to be very evil

Hat-tip to "steve" for this paper + to sidereal for supplying the full text.

We decided to compare the effects of three different puri-fied diets on body-weight development and physiological parameters in C57BL/6N mice when identical diets were either provided in powder form or as pellets.

Ok for the jist of this paper,  we are simply feeding obesity-prone mice many different diets and seeing what happens to their fat mass. The different diets are......

1) Chow=control diet in 2 varieties, hard pellet form and a form where its ground into a powder
2) "High-fat"  60% fat, 19% prot, 21% carb, both in the hard pellet and powder forms
3) "western style" 36% fat, 17% prot, 47% carb, . in hard pellet form, this was provided in 3 different flavors ( peanut, chocolate, banana ), to test the support for food reward in energy intake, but also it was provided in powdered form.

 To start with, here is the graph of body weight in response to the hard pellet forms of the diets, again, nothing we don't already know, the mice are lean on chow and obese on high-fat and western style.

Now, here comes the first interesting part of the experiment, something of which I certainly have never seen before....

This is the graph of the 3 chow/high-fat/western diets given in powdered form. Yes thats right, once you turn the hard-pellet into powder, the "chow" control diet that usually produces a lean rodent now produces an obese rodent! Infact all 3 diets in powered form produced the exact same degree of obesity. Please note, no changes were made to the "chow" diet other than it was simply ground into a powder. I.E. there was no change in macro-nutrient ratios.

But that aint all, it gets even better, 

I suppose your thinking now that since the "chow-powder" diet induced obesity, the mice must be have been gorging on extra calories? Remember the golden rule of obesity research? All that matters for fat mass balance is CICO.

Well, sorry, but the golden rule just fell flat on its face. Because the mice eating powdered chow ate just 0.4% more calories than the lean mice eating hard pelleted chow. Not statistically significant.

Infact all mice eating all 3 different versions of the powdered diets consumed pretty much the same amount of calories. Normally, mice eating high-fat consume extra calories compared to chow when both are hard-pellet form, but not so for powdered form. In powdered form, mice stop showing hyperphagia on high-fat, although they still develop obesity. There is something gruelingly suspicious here, somehow, changing the texture of the diet changes the diets satiating properties if the diet is high in fat.

This reminds me or something I have noticed when eating butter myself. Namely that, butter that is gently warmed and drank is more satiating than cold butter eaten straight from the fridge.

What about insulin, was insulin raised on the chow-powder diet?

Yup.....

Insulin on all the powder diets was absolutely through the roof. As was leptin. I have no idea if this insulin is due to hyper-secretion or insulin resistance. Despite the very high insulin levels, I would be hesitant to say that this is what is causing the obesity in the powder feed mice, although its not impossible. 

Apparently, there was no difference in body weight in the mice fed the different flavored western style diets, thats bad luck for the food reward hypothesis. 

Here, we show for the first time that a pellet-based high carbohydrate/starch diet fails to trigger obesity, whereas the same diet given in powder form produces an obese phenotype similar to a HF or W diet. While all mice receiving the high-carbohydrate C diets ingested very similar amounts of food and lost similar quantities of energy through faeces, they displayed quite different body-weight gains.

The conclusion from this paper seems to be that, powdered carbs in particular are obesogenic. Its not correct to say this of the high-fat diets because the high-fat and western diets induced similar weight gain regardless if they were hard-pellet or powder.

The thing that immediately comes to mind here is flour and flour/bakery products. This is powdered carbs that we feed to humans. I think we all know how obesogenic these foods are, for example, doughnuts, cookies, cakes, pastry, pizza bases etc. If this research paper is anything to go by the lesson here should be that we should all stay away from powdered carbs.  If your on the LC bandwagon and want to cheat, I would suggest that cheating with powdered carbs is the absolute WORST thing you can do. 

Though generally any source of carbs will make you gain weight when straying from the LC bandwagon, I would say DEFINITELY stay away from powdered carbs. Refined sugar is also quite close to the "powdered carbs" category. Extrapolating to say that "all powdered" food should be avoided however, is, not so straight forward. 

For example, Whey protein is obviously a powdered food, yet it is anything but obesogenic.  And infact is more associated with weight loss and leanness. 

There is some speculation from the researchers as to why the hard-pellet forms dont induce weight gain, including the hard-pellet form passing through the GI tract undigested and turning to SCFA in the colon, aswell as the hard-pellet form increasing postprandial thermogenesis.  

The researchers close with the thought that, all obesity research that has been done comparing high-carb chow to high-fat is essentially flawed. 

Finally, we would like to critically ask whether a pellet- based, high carbohydrate/starch diet is a proper C diet when used for comparison with HF diets. Feeding diets with . 45 % energy as fat is meanwhile accepted as a ‘gold standard’ to induce obesity in normal or transgenic mice models. The pellets of this C diet have an exceptionally hard texture and are therefore difficult to chew, to swallow and may need huge amounts of energy for handling in the gastrointestinal tract. They may also cause a loss of energy by the delivery of larger amounts of undigested starch to the microbiota and may after all produce an artificially ‘lean phenotype’.

Obesity research being flawed? Imagine that.........

Im not done yet.

 I was very depressed and felt self-destructive when I deleted everything, although im feeling a bit better now.

I still have things to post on, and obesity is not solved! I also joined Dan Ariely's free online course which I will be making a few posts on, mainly just putting up all the best and important points.