Art De Vany: Cell Competition and Cooperation, or Why Fat Cells Don't Go Willingly

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Cell Competition and Cooperation, or Why Fat Cells Don't Go Willingly

September 18, 2005 11:11 AM

This topic is a blending of evolution, metabolism, and competition; it is one of my favorites because economics is such a powerful tool for bringing these issues together. The idea is to understand cell competition and cooperation as a balance among the cell colonies that occupy and constitute a living body. Every large organization balances the interests of its constituents in a way that leaves them in a sustainable equilibrium

I will return to the topic of the title, fat and why it is so hard to get rid of, but first a few examples of the competition that exists in nature and inside our bodies to lay out the principles.

Plants and animals. Plants that are too easy to eat and are nutritious are attractive to herbivores. So, unless they can respond by limiting the ability of herbivores to digest them or by preventing the reproduction of herbivores, they will not survive the evolutionary race. Consequently, plants have many strategies to disarm, kill, or prevent the reproduction of their predators (herbivores). Grasses and the wheat that we eat that are evolved from them contain mineral sequestering substances that lock up the minerals in an herbivore, preventing mineral metabolism and growth. Phytic acid is one of the most prevalent of these and it binds zinc and calcium so that the herbivore does not develop. Phytic acid does the same thing in the human body so that a child raised on a high grain diet is deprived of the minerals he or she requires to develop. Rice, a relative of grass, does the same thing, which is one reason why northern Chinese are taller than southern Chinese; the northerners eat far less rice and more vegetables and meat.

Another trick plants have to keep from being eaten is to chemically castrate male herbivores who consume them. The chemical in this case is a form of plant estrogen that de-masculinizes the male plant eater. This happens to human males too and to females who experience too much estrogen from eating soy beans and wheat.

Yet another trick is outright poison. Plant toxins are among the most dangerous in the biological world. Ricin, the deadly toxin that kills almost instantly, is derived from soy beans. Gluten, the deadly protein that dissolves the gut of celiac disease sufferers, is one of the other protective toxins that wheat and grass related plants use.

It is all a matter of the competition for scarce resources and the defenses that one entity marshals against competitors and predators.

When it comes to cancer, strange things happen because cancer tumors compete with one another for the body's resources. Large cancers secrete substances that limit the growth of smaller cancers. Thus, when a large tumor is removed surgically, the smaller ones are now left unsuppressed and may grow rapidly. This can present a problem for the patient. After a major cancer surgery the patient may face further cancers later because they are no longer suppressed by their larger competitors.

A cancer cell is a cell that does not obey the cellular signal to commit apoptosis (cell death). It has broken away from the cooperation that generally, but not always, prevails among our body's cells. A tumor is a coalition of cooperating cells that breaks from the super coalition of the cells; the core, the sustainable equilibrium among cells in which the imputation to the cells is highest, is violated. Perhaps the equilibrium is disturbed by a virus or collateral damage from the immune system. Something renders the cancer cells less willing to cooperate with the other cells of the body and to seek their own goals. (This somewhat anthropomorphic way of putting it is harmless, but cells do not have goals per se; they just execute their programs.) It is the programs, the genes, that are changed by cancer, giving them less relatedness to the other cells. Thus, cancer cells, being farther from normal body cells in gene space, do not share the interests of the coalition of cells that constitute a living human.

Moving to the more general point, the cells in one's body are close relatives since they share the same genes. This close-relatedness tends to reduce in fighting among the cells, just as the workers in an ant colony tend not to fight because they are all sisters or brothers. The mitochondria are former plant organisms and so the cooperation between them and our own dna derived cells is somewhat lessened. So, there may be more trouble between our cells and these micro-organisms, and there is generally. Sometimes the mitochondria go into steep decline and cease to energize our cells. No one knows why, but this decline creates an energy crisis for the other cells and is a major factor in aging.

Then there is gestational diabetes. This is a situation where the fetus, in competition with the mother for the body's scarce resources, emits hormones that make the mother insulin resistant. When she is insulin resistant she cannot effectively metabolize nutrients and they go to the baby instead.

More generally, insulin resistance is a resource reallocation strategy used by various colonies of cells in the body. Insulin resistance diminishes first the ability of muscle to metabolize glucose. This makes more available to the brain, whose requirements for glucose are higher than all the other organs. muscle versus brain. This was an adaptive strategy for our ancestors who had scant access to glucose and were very active. Insulin resistant muscles were probably essential to the survival of our species. Now, it is killing us in novel ways. This is an ancient adaptation gone wrong in our present world.

Finally, fat.

Fat is an organ competing for resources. In obese people it is the largest organ or cell colony in the body. What strategies do fat cells have to shift resources to them and take them from other cells? Lots, it turns out.

Fat cells secrete many active hormones whose cumulative effect is to make other cells insulin resistant. Fat cells also become insulin resistant but at about half the rate of muscle. Thus, fat cells gain a competitive advantage over muscle cells in the competition for nutrients. In addition, fat cells secrete leptin. If the fat stores are large enough, the mass action of leptin secretion creates leptin resistance. The effect of leptin resistance is to moderate the negative effect of leptin on appetite. A similar effect holds for insulin; when we are insulin resistant, insulin does not shut down the appetite as strongly. And lipolysis is diminished.

The advantages to fat cells of insulin resistance and diminished appetite suppression are directly related to the total mass of fat. Fat cells thrive and get richer, the fatter you are. Consequently, there may be a nutrient or resource economy of scale to fat mass. Such an economy of scale would redirect nutrients to fat at such a pronounced degree that the average return to fat cells increases as fat mass increases.

No one knows if this is true, but if it were it would help to explain how large the fat mass becomes in some individuals. I would also conjecture that fat cells cause fatter individuals to expend less energy. This would be an obvious strategy for the fat colony against the muscle colony. I would go so far as to argue that some hormone or other messenger emitted by fat cells will be found with precisely that effect. It is known that the obese do expend less energy, but the reasoning has always been that they are fat because of it. Given the powerful weapons fat has to defend itself, it is also likely true that fat mass diminishes energy expenditure per unit of active muscle tissue.

Thus, just as the large cancer sites diminish the ability of smaller cancers to grow, fat may diminish the ability of other organs to grow or sustain their mass. The health consequences would be large.

Fat cells do not obey the cellular apoptosis signal and they live a very long time in the body. I would conjecture that the fatter one is the more resistant to the apoptosis signals fat cells become. This would make fat cell turnover per unit of fat less for the obese than for the non obese.

So, what do you do to get rid of those fat cells who won't give up their contents to other cells and who refuse to die?

You have to starve them, but not by starving your other organs. You must change the allocation of resources away from fat and to the other organs and muscle. You must empty the muscle of its glycogen stores so that muscle cells become highly sensitive to insulin, in spite of the attempts of fat cells to deter this. Aerobics won't be enough because 1. if you are obese you are probably made "lazy" by that very fat you are trying to lose, 2. you will not drain enough glycogen, and 3. you will not sufficiently alter the hormone profile to redirect nutrients away from fat. You have got to do glycogen-draining anaerobic exercise. And, you have to eat less, but intermittently as in every other day eating. This begins to attack those fat cells in a way against which they cannot effectively defend themselves.

· Evolutionary Fitness

Comments

As far as the tabata studies go my understanding was that they were done on competitive athletes - perhaps they did not have much fat to lose in the first place.

I have used Art's advice and got amazing results after struggling to lose any weight at all with convention gym diets and exercise programs.

Losing a large amount of body fat in a short time and then keeping it off for nearly 2 years now.

I'm definitely a believer on developing more fast twitch muscle - which requires some form of anaerobic training.

Fast twitch muscle burns more calories - even when resting. Fast twitch muscle and keeping your insulin low through the right diet and eating patterns are the key for me.

That said - walking is all good.

Posted by: Hone Watson at September 23, 2005 6:58 PM

All of Ellington Darden's studies had the people on a calorie-restricted diet - that is what was behind the large weight loss. Also, strength training is more intense than aerobic exercise and will burn more calories (and also encourage the body to hold onto lean mass).

To say it differently, an hour of strength training will burn more calories both during and after than an hour of walking. But how many people can do an hour of strength training per day without getting overtrained? On the other hand, most people can do an hour of walking per day fairly easily.

And Art is prescribing brief periods of anaerobic exercise. So a high enough volume of low-intensity work (walking) will necessarily produce more fat loss than a small volume of anaerobic work. Again, if you look at the original Tabata and Treblay interval training studies, you will find the subjects lost very little fat.

Maybe mentioning this study will clear things up:

The effect of combined aerobic and resistance exercise training on abdominal fat in obese middle-aged women.
J Physiol Anthropol Appl Human Sci. 2003 May;22(3):129-35.

One group did 6 hours of aerobics per week and lost roughly 12 pounds over twelve weeks. Another group did 3 hours of aerobics and 3 hours of strength training and lost roughly 26 pounds.

A combination of the two is clearly better, but Art's exact words were "aerobics won't be enough" and "You have got to do glycogen-draining anaerobic exercise." I am instead pointing out that one can lose weight through aerobic exercise alone - I am not suggesting it is the best method.

Posted by: matt m at September 21, 2005 9:49 AM

Matt M,

All of Ellington Darden's studies found the exact opposite of what you are claiming. The group doing the strength training typically lost the most (by a large amount) and the group doing a mix of strength training and aerobics and the group doing aerobics lost the least. You may find fault with his studies but the methodology appeared sound to me and there was a large sample size, n=100 for each group.

David

Posted by: David at September 21, 2005 6:21 AM

Hone,

Yes, everything you said about anaerobic exercise is true, but it is far overrated in terms of fat loss. If you look at the actual research studies on interval training, you will see that the subjects lost very little fat. If you look at studies where subjects started weightlifting 2-3 times per week, you will also find they lost very little fat. In comparison, studies show that walking an extra one hour per day will yield roughly one pound of fat loss per week.

Art is in favor of walking, as shown by his previous posts. It is obviously part of our evolutionary heritage, and should be part of a healthy lifestyle.

I know Art is against jogging and the like, but the research does show a person can lose fat through aerobic activity. That was my disagreement with an otherwise very good, very informative post.

Posted by: matt m at September 20, 2005 8:47 PM

Matt,

Low intensity aerobics may burn fat at a higher percentage compared to anaerobic exercise, but anaerobic exercise has been shown to burn more fat overall because it burns far more calories overall.

When you stop your aerobic exercise, you stop burning fat, where as with anaerobic exercise you can keep burning additional calories for up to 24 hours+ due to the hormone drives produced by the anaerobic exercise and the repair and building of muscle.

However, I personally believe, walking and hiking over varying terrains on a daily basis should be an essential part to a normal active lifestyle.

Not that I'm trying to put words in Art's mouth but if you look at other stuff Art has written, you will see that he has nothing against walking, and when he talks about aerobics, he's talking more about jogging, ticking up the kilometers (and hours) on cardio machines at the gyms, and aerobic classes etc

Posted by: Hone Watson at September 20, 2005 6:15 PM

Great post, though I disagree with some of the conclusions regarding aerobics. Several studies, such as Ross, Freeman, and Janssen (2000), show that a high enough volume of low-intensity aerobics (walking an hour a day) is sufficient to lose fat. Low-intensity aerobics will preferentially burn fat, so it won't matter in this case if the glycogen stores are full or not.

As you mentioned, aerobics by itself will not alter the hormone profile (encourage the body to hold onto lean mass), so some high-intensity work is necessary as well.

Posted by: matt m at September 20, 2005 9:28 AM

Really interesting comments and I hope you devote more to this little understood subject in your book. Do you think that there is a physiological difference between men and women's fat cells? If so, would your general comments for consistent and prolonged weight loss still hold true?
tks
CJ

Posted by: cj at September 20, 2005 9:17 AM

Cell Competition and Cooperation, or Why Fat Cells Don't Go Willingly

September 18, 2005 11:11 AM

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