Treating obesity from within the small intestine -- pro/cons?

[Green Xenon]

Hi:

 

I asked a similar speculative question before but am still obsessed with hi-tech measures to treat obesity. I apologize profusely if anyone is annoyed.

 

The following is a theoretical cure of obesity I’m brainstorming about.

 

The patient’s small intestine is populated by hypothetical synthetic bacteria that fit all the following characteristics:

 

1. Not gram-negative

2. Free of lipopolysaccharide

3. Non-pathogenic

4. Aerotolerant-anaerobic

5. Non-allergenic

6. Use homolactic acid fermentation as their only source of energy.

 

These bacteria are present in a pill the patient ingests.

 

These bacteria are designed so that they specifically feed solely on all carbohydrates [in meals that that the patient eats] that will directly on indirectly cause a rise in blood sugar – without affecting other carbohydrates. The bacteria breakdown all these unwanted carbohydrates -- including galactose -- to glucose and then ferment the glucose completely into lactate. Each bacterium converts glucose to lactate at the highest-possible rate. In the unlikely event that the patient ingests glucose, these bacteria will immediately ferment the glucose to lactate.

 

Since homolactate fermentation does not generate gases – such as CO2 – the patient will not experience the bloating that would occur in other types of fermentations.

 

Due to lack of glucose in the bloodstream, the body will be forced to use fat for energy and patient will eventually lose all of his/her adipoctyes. The central nervous system will use ketones for energy, as a substitute for glucose.

 

End result: the patient is no longer obese.

 

However, nothing is without drawbacks. Here are two that I immediately envision:

 

1. Breasts will disappear

2. Patient will difficulty sitting down due to absence of the fat that would otherwise protect the buttocks

 

Are there anymore *medical* or *cosmetic* disadvantages to this hypothetical treatment of obesity?

 

 

Thanks,

 

GX

Edited October 2, 2011 by Green Xenon

[pantheory]

Green Xenon,

 

I feel certain that something like this will be developed in the future but with conceivable side effects and required oversight. Unless you are in this field and have the funding to do it yourself, it would be seemingly far better to go with one of procedures of present technology such as a lap-band or the gastric bypass procedure concerning weight loss. The lap-band is not difficult to reverse if too many problems result.

[Green Xenon]

Green Xenon,

 

I feel certain that something like this will be developed in the future but with conceivable side effects and required oversight. Unless you are in this field and have the funding to do it yourself, it would be seemingly far better to go with one of procedures of present technology such as a lap-band or the gastric bypass procedure concerning weight loss. The lap-band is not difficult to reverse if too many problems result.

 

 

Hi Pantheory:

 

Thanks for your response.

 

Sorry for my persistence on this topic but I have a question regarding another speculative cure for obesity.

 

Let's assume I’m the average 27-year-old male human.

 

It is well-known that the small intestine contains enterocytes which absorb substances -- such as carbohydrates from foods -- into the bloodstream. Currently, these enterocytes rely on aerobic respiration [from glucose and oxygen via their supply of blood from capillaries].

 

Here is where the speculative element enters play: the enterocytes of the small intestine develop organelles that rely on solely on homolactate fermentation for energy. Glucose from digested food enters these organelles to provide them with fuel to initiate the homolactate fermentation. Homolactate fermentation does not generate CO2, the patient being treated will not experience any bloating. Each of these organelles converted glucose to lactate at the fastest rate possible. There are also as many of these new organelles as possible without hindering the absorption of nutrients other than carbohydrates. Any simple sugars *other* than glucose [such as fructose and galactose] are digested by these organelles and converted to glucose, which provides energy for these organelles. Any simple sugar -- that would otherwise be absorbed into the bloodstream -- goes through this conversion to glucose. NO amount of glucose or any simple sugar is absorbed into the bloodstream to ANY extent. Equally *important* is that the waste product of fermentation [i.e. lactate] is not at all absorbed into the bloodstream, instead, all of the lactate molecules are pumped out of these organelles and back into the small intestine. These molecules of lactate are then excreted in the stool via the colon.

 

These homolactate-fermenting organelles do NOT receive any glucose from the blood, but instead feed on the glucose resulting from ingestion of digestible carbohydrates.

 

If, for whatever reason, these organelles are not receiving a sufficient amount of glucose -- such as if/when the patient fasts -- they don't die or experience any damage to any extent. Instead, these organelles enter a metabolically-inactive [dormant] state. When glucose is again present, these organelles will resume their process of converting glucose to lactate. These organelles only die when the attached enterocyte dies. After the programmed cells death [apoptosis] of the current enterocytes, new enterocytes will germinate. These new enterocytes will keep sprouting those glucose-eating organelles so this conversion of simple carbohydrates to lactate will continue for the rest of my life.

 

Last -- but not least -- these organelles have another function. They completely prevent the entry of the following substances into the enterocytes:

 

1. Glycerol

2. Cholesterol

3. Saturated fatty acids

 

As soon as any of the above 3 molecules enter any organelle, the organelle channels the undesired molecule out and back into the small intestine to be excreted in the stools via the colon. This will decrease the concentration of cholesterol and LDL in the bloodstream.

 

Let's say my small intestine suddenly experiences the above metamorphosis.

 

In addition, let's say I take part in the optimum/ideal amounts, durations, intensities, and repetitions of strength-training, flexibility-training -- [such as stretching], and body-building exercises with the optimum/ideal amount of rest in between workouts. However, I do absolutely *no* cardiovascular or aerobic exercises.

 

Let's also say that my diet consists solely of Italian and Indian sweets/desserts along with fruits covered in dairy cream. In addition, instead of eating 3 large meals a day, I eat very many amounts of very small variable-sized meals a day in such a manner that I get the ideal amount of protein per day for my muscular health. Last but not least, the meal sizes vary such that the 1st meal of the day is the largest, and the last meal of the day is the smallest. As the day goes on each meal gets smaller. This routine is similar to the "eats breakfast like a king, lunch like a prince, and dinner like a pauper" type of meal plan, except that is involves much larger amounts of much smaller meals.

 

In terms of water, I also get drink the ideal/optimum amount for health [including muscle strength/size]. I also get the optimum amount of sleep each night and wake up at 5:00 AM each morning.

 

Now, it's obvious that fruits as well as sweets/desserts of any kind tend to be rather low in protein. This means that if I'm getting the ideal amount of protein from such foods, the result will be an extreme excess of lactate in the colon.

 

Final note: All the foods I consume are completely natural and organic. They do not involve any entity -- such as pesticides or industrial pollutants -- that would cause them to be considered un-natural or non-organic. No trans fats or margarine either. Lot's of butter and cream, though!!

 

What will happen if I start and maintain this lifestyle -- in terms of diet and exercise -- after my small intestine goes through the aforementioned changes?

 

Here are my guesses.

 

1. Due to lack of glucose in the bloodstream, the body will be forced to use fat for energy and I will eventually lose all of my adipoctyes. The central nervous system will use ketones for energy, as a substitute for glucose.

 

2. Since body fat will be lost, my breasts will no longer be noticeable when clothed [even men have some amount of visible breast tissue!]. In addition, I will have a hard time sitting due to the absence of fat in my buttocks.

 

3. My muscle mass will increase -- due to the above diet and exercise regime.

 

4. Diarrhea due to colonic irritation caused by the acidity of lactate.

 

5. Steatorrhea due to presence of excessive glycerol, cholesterol, and saturated fatty acids in the stool

 

What else would happen with me in this speculative situation? How long would I survive? What disadvantages would I experience other than #2, #4, and #5 of my above guesses?

 

 

Thanks again,

 

GX

Edited October 7, 2011 by Green Xenon

[Realitycheck]

You can't forget insulin resistance issues and the likelihood that your body will burn muscle for energy over fat when you are eating these unhealthy foods which raise insulin resistance.

Also, it would be greatly beneficial to employ something called nutrient partitioning, which basically stipulates that you should only eat certain foods at the proper time of the day, when your body utilizes the nutrients most optimally, such as grains and starches in the morning and lunch, when your body needs the energy, and slow-digesting greens and essential fatty acids at night, which are also slow-digesting. Moral of the story is that it makes no sense to carboload at night if you are going to sleep it all off and waste the energy, but you alluded to that, to an extent. Also, every teaspoon of sugar you eat throughout the day prevents your body from deriving energy from fat at all for a period of time and if your diet consists of ten deserts spread out throughout the day, then that pretty much short-circuits all your efforts.

 

Also, if your entire body utilizes about 2,000 calories a day to function properly, think about how many bacteria it would take to dispose of a fraction of that. You're going to take a stomach full of bacteria, cram it into your small intestine just to digest one candy bar a day, while your body digests ten candy bars? These bacteria hardly sound up to the task.

 

The bacteria that are there help with digestion but don't really compare in scope. Energy in, energy out. What function could these bacteria possibly have other than bloating up your digestive system to fantastic proportions in no time?

Edited October 7, 2011 by Realitycheck

[Green Xenon]

You can't forget insulin resistance issues and the likelihood that your body will burn muscle for energy over fat when you are eating these unhealthy foods which raise insulin resistance.

Also, it would be greatly beneficial to employ something called nutrient partitioning, which basically stipulates that you should only eat certain foods at the proper time of the day, when your body utilizes the nutrients most optimally, such as grains and starches in the morning and lunch, when your body needs the energy, and slow-digesting greens and essential fatty acids at night, which are also slow-digesting. Moral of the story is that it makes no sense to carboload at night if you are going to sleep it all off and waste the energy, but you alluded to that, to an extent. Also, every teaspoon of sugar you eat throughout the day prevents your body from deriving energy from fat at all for a period of time and if your diet consists of ten deserts spread out throughout the day, then that pretty much short-circuits all your efforts.

 

Also, if your entire body utilizes about 2,000 calories a day to function properly, think about how many bacteria it would take to dispose of a fraction of that. You're going to take a stomach full of bacteria, cram it into your small intestine just to digest one candy bar a day, while your body digests ten candy bars? These bacteria hardly sound up to the task.

 

The bacteria that are there help with digestion but don't really compare in scope. Energy in, energy out. What function could these bacteria possibly have other than bloating up your digestive system to fantastic proportions in no time?

 

1. Insulin resistance is unlikely because carbs aren't entering the bloodstream.

 

2. You're right about the bloating aspect.

Edited October 7, 2011 by Green Xenon

[Psycho]

I briefly read your idea, which seemed vastly over complicated, what is your field of expertise?

 

Really all you need is bacteria which breakdown fats within the small intestine, if bacteria within the intestines can be engineered to break down 20% of the saturated fat consumed to unsaturated/poly-unsaturated fat that will reduce the energy levels of the absorbed compounds and therefore the energy received by the body as well as the level of LDLP created, therefore causing the body to create a more sustainable balance.

 

It isn't about completely stopping the absorption of the nutrients as this will lead to people starving from a lack of them; A sustainable approach is necessary.

[Green Xenon]

I briefly read your idea, which seemed vastly over complicated, what is your field of expertise?

 

Really all you need is bacteria which breakdown fats within the small intestine, if bacteria within the intestines can be engineered to break down 20% of the saturated fat consumed to unsaturated/poly-unsaturated fat that will reduce the energy levels of the absorbed compounds and therefore the energy received by the body as well as the level of LDLP created, therefore causing the body to create a more sustainable balance.

 

It isn't about completely stopping the absorption of the nutrients as this will lead to people starving from a lack of them; A sustainable approach is necessary.

 

1. I'm a biology major @ Cal Poly Pomona

 

2. Why not make a method in which all molecules of glucose, fructose, galactose, glycerol, cholesterol, & saturated fatty acids -- regardless of their concentrations in the given meal -- will fail completely to be absorbed into the enterocytes?

 

3. This isn't about stopping the absorption of all nutrients, just the undesirable ones -- such as what is mentioned in #2

Edited October 7, 2011 by Green Xenon

[Psycho]

1. I'm a biology major @ Cal Poly Pomona

 

2. Why not make a method in which all molecules of glucose, fructose, galactose, glycerol, cholesterol, & saturated fatty acids -- regardless of their concentrations in the given meal -- will fail completely to be absorbed into the enterocytes?

 

3. This isn't about stopping the absorption of all nutrients, just the undesirable ones -- such as what is mentioned in #2

Well point 2 and 3 are contradictory, glucose, fructose, galactose, glycerol, cholesterol, & saturated fatty acids, aren't undesirable.

 

If you stop fatty acid absorption you wouldn't gain any vitamin A and would go blind and this is just one of many examples of why they aren't bad, i'll take some statins over being blind any day of the week.

Edited October 7, 2011 by Psycho

[Green Xenon]

Well point 2 and 3 are contradictory, glucose, fructose, galactose, glycerol, cholesterol, & saturated fatty acids, aren't undesirable.

 

Actually they are undesirable. See below.

 

If you stop fatty acid absorption you wouldn't gain any vitamin A and would go blind and this is just one of many examples of why they aren't bad, i'll take some statins over being blind any day of the week.

 

Incorrect.

 

Note that this hypothetical system of organelles *does* allow unsaturated fatty acids and fat-soluble vitamins to pass into the enterocytes. However, it selectively filters out the unwanted lipids -- cholesterol, glycerol, and saturated fatty acids. These "fatty wastes" are then pumped back into the small intestine and finally excreted in the stools via the colon -- spelling the end of constipation as we know it.

 

We don't need "fatty wastes", as our bodies are fully-capable of producing them [a process which helps consume calories that would other turn into adipose].

Edited October 7, 2011 by Green Xenon

[Psycho]

Actually they are undesirable. See below.

 

 

 

Incorrect.

 

Note that this hypothetical system of organelles *does* allow unsaturated fatty acids and fat-soluble vitamins to pass into the enterocytes. However, it selectively filters out the unwanted lipids -- cholesterol, glycerol, and saturated fatty acids. These "fatty wastes" are then pumped back into the small intestine and finally excreted in the stools via the colon -- spelling the end of constipation as we know it.

 

We don't need "fatty wastes", as our bodies are fully-capable of producing them [a process which helps consume calories that would other turn into adipose].

Wait so you want to genetically engineer new organelles into our cells?

 

I thought you were actually talking about doing something practical, ethically viable and possible in the next 50 years.

 

Think someone needs to conclusively figure out how proteins are directed to organelles for processing before you start making artificial organelles, you have kind of put the cart before the horse, and the horse is a sheep and the wheel hasn't been invented yet.

[Green Xenon]

Wait so you want to genetically engineer new organelles into our cells?

 

I thought you were actually talking about doing something practical, ethically viable and possible in the next 50 years.

 

Think someone needs to conclusively figure out how proteins are directed to organelles for processing before you start making artificial organelles, you have kind of put the cart before the horse, and the horse is a sheep and the wheel hasn't been invented yet.

 

Sorry, "organelle" maybe the wrong term to use here.

 

Perhaps a "secondary" enterocyte could be engineered to do that aforementioned tasks. These secondary enterocytes could pair to the primary [natural & already-existing] enterocytes in the small intestine and do the tasks of:

 

1. Fermenting glucose, galactose, and fructose to lactate -- without letting any of these molecules enter the primary enterocytes.

2. Re-routing glycerol, cholesterol, lactate, and saturated fatty acids back into the small intestine to be excreted in the stools via the colon.

3. Allow the entry of other nutrients [including fat-soluble vitamins and unsaturated fatty acids] into the primary enterocytes.

 

If this worked out, what would be the disadvantages that I haven't spoken of yet?

Edited October 8, 2011 by Green Xenon

[Psycho]

Sorry, "organelle" maybe the wrong term to use here.

 

Perhaps a "secondary" enterocyte could be engineered to do that aforementioned tasks. These secondary enterocytes could pair to the primary [natural & already-existing] enterocytes in the small intestine and do the tasks of:

 

1. Fermenting glucose, galactose, and fructose to lactate -- without letting any of these molecules enter the primary enterocytes.

2. Re-routing glycerol, cholesterol, lactate, and saturated fatty acids back into the small intestine to be excreted in the stools via the colon.

3. Allow the entry of other nutrients [including fat-soluble vitamins and unsaturated fatty acids] into the primary enterocytes.

 

If this worked out, what would be the disadvantages that I haven't spoken of yet?

Ignoring the fact that it is even harder to add a "cell type" to a system than it is to add an organelle to a cell.

 

1. What do you mean by fermenting, humans cells don't ferment things, glycolysis breaks down sugars to pyruvate and then it is hydrolysed to lactate and this isn't a good idea as it pertains pumping acid into your small intestine, sprint down the road and ask me if you want the feeling in your muscles to be in your abdomen every time you eat a burger.

 

2/3. How do allow the entry of fat soluble vitamins without allowing in fat? The only solution would be to constantly cycle it in and out of these cells all the way through the small intestine to allow fat soluble vitamin uptake, which would take so much energy that considering you are no longer getting any of a primary important energy source (fat) would increase rates of malnutrition.

 

Paper on Vitamin A absorption - Just read the paragraph on "Intestinal Absorption of Retinol"

[Green Xenon]

Ignoring the fact that it is even harder to add a "cell type" to a system than it is to add an organelle to a cell.

 

1. What do you mean by fermenting, humans cells don't ferment things, glycolysis breaks down sugars to pyruvate and then it is hydrolysed to lactate and this isn't a good idea as it pertains pumping acid into your small intestine, sprint down the road and ask me if you want the feeling in your muscles to be in your abdomen every time you eat a burger.

 

2/3. How do allow the entry of fat soluble vitamins without allowing in fat? The only solution would be to constantly cycle it in and out of these cells all the way through the small intestine to allow fat soluble vitamin uptake, which would take so much energy that considering you are no longer getting any of a primary important energy source (fat) would increase rates of malnutrition.

 

Paper on Vitamin A absorption - Just read the paragraph on "Intestinal Absorption of Retinol"

 

Thanks for the link.

 

1. If lactate is flowing through the small intestine into the colon then excreted, will there be a painful sensation similar to that of lactate build-up in skeletal muscle?

 

2. Fatty acids are allowed to enter the lacteals supplying the enterocytes as long as they are unsaturated. BTW, the excess energy requirement you describe is probably a good thing as it would force the body to increase it's metabolism and burn even more fat. The source of energy for this are unsaturated fatty acids from food as well as any fatty acids resulting from lipolysis of the visceral adipose tissue.

Edited October 8, 2011 by Green Xenon

[Psycho]

Thanks for the link.

 

1. If lactate is flowing through the small intestine into the colon then excreted, will there be a painful sensation similar to that of lactate build-up in skeletal muscle?

 

2. Fatty acids are allowed to enter the lacteals supplying the enterocytes as long as they are unsaturated. BTW, the excess energy requirement you describe is probably a good thing as it would force the body to increase it's metabolism and burn even more fat. The source of energy for this are unsaturated fatty acids from food as well as any fatty acids resulting from lipolysis of the visceral adipose tissue.

1. I imagine it wouldn't be as bad, but I don't think you will feel great either it is acid in a sensitive area of the body after all, it might have a similar sensation to acid reflux, not great.

 

2. Do you have a transport pathway that allows selective uptake of unsaturated fats and not saturated ones?

 

The body wouldn't increase its metabolism, it would stay the same. What happens when you aren't obese any more, you seem to be completely missing the point of if the system is effective the person would end up dead, there are also essential fatty acids that can't be created or are they also going to be magically selectively transported while others aren't.

 

The only successful way currently to achieve this would be as an embryo and the child would end up dead due to malnutrition, or on a ridiculous diet even though they haven't even had a chance to get obese.

 

The whole idea massively over complicates the idea, people should just go for a walk.

Edited October 8, 2011 by Psycho

[John Cuthber]

They don't call them "essential" fatty acids because they think it's a cool name.

http://www.ncbi.nlm.nih.gov/pubmed/12728744

 

" In the unlikely event that the patient ingests glucose, these bacteria will immediately ferment the glucose to lactate. "

Practically all foods contain glucose because practically everything alive contains glucose. It's hardly unlikely.

 

"The patient’s small intestine is populated by hypothetical synthetic bacteria that fit all the following characteristics:

 

...

6. Use homolactic acid fermentation as their only source of energy. "

So they will be out-competed by bacteria that have more than one string to their bow and will become extinct.

 

"The central nervous system will use ketones for energy, as a substitute for glucose."

I don't think it can. I'm sure it can only run on glucose (via lactate I think).

 

"all of the lactate molecules are pumped out of these organelles and back into the small intestine. These molecules of lactate are then excreted in the stool via the colon."

 

A few days of that (shitting strong acid) and you would wish you had just joined a gym.

Also, what's to stop the lactate being eaten by other bacteria that are present? One possibility is the conversion to hydrogen and acetic acid. Does that sound like fun?

[Green Xenon]

Ok, I'm learning a lot here.

 

Let's forget about the blocking of lipids -- of any kind. Let's allow them to enter the lacteals like they normally would.

 

Let's also forget about directly converting the glucose to lactate.

 

I'm changing this hypothetical situation to the following.

 

Carbohydrates that would normally enter the enterocytes -- such as glucose, galactose, and fructose -- do enter. Galactose and fructose are converted to glucose as they normally would be. However, there is a 100% effective theoretical mechanism that prevents the glucose from entering the bloodstream. Right before any molecule of glucose can enter the bloodstream [as the glucose normally would], the glucose molecule is instead instantly transported out into the lumen of small intestine and then excreted in the stools via the colon.

 

Supposing -- against all odds -- such a mechanism were enabled and was working at 100% efficiency. What symptoms would I experience if I follow the aforementioned diet and exercise plan?

[Psycho]

This hypothesis now sounds similar to the fundamental principals of the aktins diet which removes almost all carbohydrates from the diet, there is no essential need for carbohydrates they can all be produced from fats and proteins via various cellular pathways.

 

The real question is do you have any proposed system to stop the metabolism of external carbohydrate?

Edited October 9, 2011 by Psycho

[Green Xenon]

This hypothesis now sounds similar to the fundamental principals of the aktins diet which removes almost all carbohydrates from the diet, there is no essential need for carbohydrates they can all be produced from fats and proteins via various cellular pathways.

 

The real question is do you have any proposed system to stop the metabolism of external carbohydrate?

 

You're absolutely right. What I'm doing is an Atkins's "induction in a pill" approach. So, the consumer will pretty be in the induction phase for the rest of his/her life regardless of what he/she eats.