Robert Santana RD SSC: Bodyfat, Health, and Longevity

[Robert Santana]

Huh, interesting. Is there a way to control what kind of fat you put on, whether it be ectopical or subcutaneous? Sumo wrestlers come to mind. I've heard while they are large, their lifestyle allows them to keep visceral fat content low.

Great question. The reason sumo wrestlers have a low visceral adipose tissue content is because of their training. If they continue the same diet upon cessation of training, VAT accumulates and so does their risk for cardiometabolic diseases. Now keep in mind these guys. are athletes; obese athletes but athletes nonetheless. So they are training a lot so we can't really generalize the effects of a sumo wrestling training program to folks who are just exercising recreationally. In general, the take away here is that exercise has been shown to bend the curve when it comes to blood pressure, insulin sensitivity, and vascular function in the absence of weight loss.

[Yonason Herschlag]

Impossible to measure this but if the theory holds true then your body would go into adaptive thermogenesis and your metabolic rate would adjust to meet your current intake.

Thank you for your presentation Robert, I found it very interesting. And I agree with your above response, that when cutting calories the body adapts by slowing the metabolism.

Concerning the idea proposed that we can't lose fat cells, from what I have read that's not true.

The normal lifespan of a fat cell is approximately 8.5 years. Roughly 10 percent of one’s fat cells die/self-destruct and are replaced each year. Ten percent of fifty billion fat cells (amount of a typical overweight, middle-aged person) is five billion fat cells. If we divide that by 365 days per year, we get roughly fourteen million; when we divide this number by twenty-four hours, we get roughly six hundred thousand. So in a quarter hour, a person with fifty billion fat cells experiences the apoptosis of roughly one hundred and fifty thousand fat cells.

Fat Cell Apoptosis via Vitamins A and D and Calcium
These three nutrients are essential for destroying old fat cells (and vitamin A also represses the reproduction of new fat cells). Here’s the conclusion of one recent study done in June 2014: “High vitamin D and Calcium intakes activate the Calcium (2+)–mediated apoptotic pathway in adipose tissue. The combination of D3 plus Calcium was more effective than D3 or Calcium alone in decreasing adiposity.”

Another study comes to essentially the same conclusion, stressing the importance of high doses of vitamin D and calcium.

According to the following study and mega-analysis (on rats, not humans):
“Feeding a high but non-toxic dose of vitamin A (129 mg/kg diet) resulted in a significant reduction in the adiposity index and retroperitoneal white adipose tissue (RPWAT) weight in obese rats while a marginal reduction was observed in lean rats. The feeding of a vitamin A-deficient diet to rats resulted in increased adiposity and body weight gain. Recent studies substantiate the concept that adipocyte deletion by apoptosis is a significant contributor to the regulation of adipose tissue mass and its loss during weight reduction. Retroperitoneal adipose tissue cell density data clearly showed that chronic vitamin A challenging through diet had no impact on cell size. This formed the basis for our hypothesis that vitamin A-mediated loss of adipose tissue could be through altered (decreased) adipocyte number rather than size.”

[tfranc]

Great question. The reason sumo wrestlers have a low visceral adipose tissue content is because of their training. If they continue the same diet upon cessation of training, VAT accumulates and so does their risk for cardiometabolic diseases. Now keep in mind these guys. are athletes; obese athletes but athletes nonetheless. So they are training a lot so we can't really generalize the effects of a sumo wrestling training program to folks who are just exercising recreationally. In general, the take away here is that exercise has been shown to bend the curve when it comes to blood pressure, insulin sensitivity, and vascular function in the absence of weight loss.

Very interesting. Would you say that their training enables them to put on subcutaneous fat instead of visceral, or just that it just keeps visceral fat off and they would have the same amount of subcutaneous fat whether they trained or not? Hope that question makes sense.

One last question I had:

Just out of curiosity I did some research on their training and lifestyle, and it looks like the bulk of their training is a lot of HIIT and anaerobic work. Is it safe to assume that anaerobic exercise, like lifting weights, has a positive impact on visceral fat over other kinds of physical activity?

[Robert Santana]

Thank you for your presentation Robert, I found it very interesting. And I agree with your above response, that when cutting calories the body adapts by slowing the metabolism.

Concerning the idea proposed that we can't lose fat cells, from what I have read that's not true.

The normal lifespan of a fat cell is approximately 8.5 years. Roughly 10 percent of one’s fat cells die/self-destruct and are replaced each year. Ten percent of fifty billion fat cells (amount of a typical overweight, middle-aged person) is five billion fat cells. If we divide that by 365 days per year, we get roughly fourteen million; when we divide this number by twenty-four hours, we get roughly six hundred thousand. So in a quarter hour, a person with fifty billion fat cells experiences the apoptosis of roughly one hundred and fifty thousand fat cells.

Fat Cell Apoptosis via Vitamins A and D and Calcium
These three nutrients are essential for destroying old fat cells (and vitamin A also represses the reproduction of new fat cells). Here’s the conclusion of one recent study done in June 2014: “High vitamin D and Calcium intakes activate the Calcium (2+)–mediated apoptotic pathway in adipose tissue. The combination of D3 plus Calcium was more effective than D3 or Calcium alone in decreasing adiposity.”

Another study comes to essentially the same conclusion, stressing the importance of high doses of vitamin D and calcium.

According to the following study and mega-analysis (on rats, not humans):
“Feeding a high but non-toxic dose of vitamin A (129 mg/kg diet) resulted in a significant reduction in the adiposity index and retroperitoneal white adipose tissue (RPWAT) weight in obese rats while a marginal reduction was observed in lean rats. The feeding of a vitamin A-deficient diet to rats resulted in increased adiposity and body weight gain. Recent studies substantiate the concept that adipocyte deletion by apoptosis is a significant contributor to the regulation of adipose tissue mass and its loss during weight reduction. Retroperitoneal adipose tissue cell density data clearly showed that chronic vitamin A challenging through diet had no impact on cell size. This formed the basis for our hypothesis that vitamin A-mediated loss of adipose tissue could be through altered (decreased) adipocyte number rather than size.”

All great questions Yonason! So under normal physiological conditions we turnover ~10% of our fat cells per year via apoptosis. This means that old cells are dying and being replaced by new cells. So technically yes fat cells are lost but they are replaced at the rate that they are lost, suggesting no net change. Its a homeostatic mechanism designed to maintain "normal" fat cell size (which varies between individuals). Weight loss studies done on both obese individuals as well as involuntary weight loss in cachectic individuals with cancer have both reported a reduction in fat cell size in the absence of a reduction in fat cell number. To be fair, the role of micronutrient supplementation is still largely unexplored in humans though, so no doubt there are many unanswered questions out there.

In the Sergeev study, they reported difference in weight gain and a lower terminal body weight. This means that the animals supplemented, with C, D, or C+D, with C+D having the greatest effect, gained the least amount of weight. The point here is weight was still gained. Epididymeal fat pad weight, which is a mass of tightly packed fat cells located specifically around the heart, was significantly lower in the C+D group, which again means that it weighed less. Retroperitoneal fat were also lower in the groups receiving supplements.

Similar in the Jayakumar paper. They are reporting less weight gain yet weight gain is still taking place. Both studies are reporting an increase in markers of apoptosis, which in theory, suggests that it may be possible to increase apoptosis and reduce lipogenesis, which, over the long term, may lead to a reduction in fat cell number in obese rats and/or individuals. However, the verdict is still not out there and long term human studies would need to be conducted to see if a short term inhibition of apoptotic pathways might lead to a net reduction in fat cell number.

Below is a good review paper on this. Hope this helps!!

Dynamics of fat cell turnover in humans. - PubMed - NCBI

[Robert Santana]

Very interesting. Would you say that their training enables them to put on subcutaneous fat instead of visceral, or just that it just keeps visceral fat off and they would have the same amount of subcutaneous fat whether they trained or not? Hope that question makes sense.

One last question I had:

Just out of curiosity I did some research on their training and lifestyle, and it looks like the bulk of their training is a lot of HIIT and anaerobic work. Is it safe to assume that anaerobic exercise, like lifting weights, has a positive impact on visceral fat over other kinds of physical activity?

Of course! So HIIT, LSD, and RT all improve insulin sensitivity, BP, and glucose tolerance. When a person becomes hyperinsulinemic (meaning insulin is high), this inhibits lipolysis (the breakdown of fat). Under normal conditions this is a temporary response to eating a meal. In the insulin resistant state, this is happening continuously. This may lead to a compensatory deposition of visceral fat, which will then release free fatty acids in the blood. However, this is occurring during a time when we don't need additional circulating free fatty acids. This creates problems for the liver because if this persists then you get intrahepatic fat deposition (fat storage in the liver), which worsens the insulin resistant state, and eventually leads to a full onset of diabetes.

In the case of our sumo wrestlers, they are blunting most of this by training. If they switch to a sedentary lifestyle and maintain their current fat stores, their risk of experiencing the above increases.

[Yonason Herschlag]

All great questions Yonason! So under normal physiological conditions we turnover ~10% of our fat cells per year via apoptosis. This means that old cells are dying and being replaced by new cells. So technically yes fat cells are lost but they are replaced at the rate that they are lost, suggesting no net change. Its a homeostatic mechanism designed to maintain "normal" fat cell size (which varies between individuals). Weight loss studies done on both obese individuals as well as involuntary weight loss in cachectic individuals with cancer have both reported a reduction in fat cell size in the absence of a reduction in fat cell number. To be fair, the role of micronutrient supplementation is still largely unexplored in humans though, so no doubt there are many unanswered questions out there.

In the Sergeev study, they reported difference in weight gain and a lower terminal body weight. This means that the animals supplemented, with C, D, or C+D, with C+D having the greatest effect, gained the least amount of weight. The point here is weight was still gained. Epididymeal fat pad weight, which is a mass of tightly packed fat cells located specifically around the heart, was significantly lower in the C+D group, which again means that it weighed less. Retroperitoneal fat were also lower in the groups receiving supplements.

Similar in the Jayakumar paper. They are reporting less weight gain yet weight gain is still taking place. Both studies are reporting an increase in markers of apoptosis, which in theory, suggests that it may be possible to increase apoptosis and reduce lipogenesis, which, over the long term, may lead to a reduction in fat cell number in obese rats and/or individuals. However, the verdict is still not out there and long term human studies would need to be conducted to see if a short term inhibition of apoptotic pathways might lead to a net reduction in fat cell number.

Below is a good review paper on this. Hope this helps!!

Dynamics of fat cell turnover in humans. - PubMed - NCBI

Thanks for responding Robert. The article you linked to looks very interesting, but I can't access the full article without paying $20. If I understood the summary correctly, it is claiming that the total number of fat cells doesn't change after reaching adulthood. And that makes no sense to me. The average size (weight) of an adult fat cell is about 0.6 micrograms, but they can vary in size from 0.2 micrograms to 0.9 micrograms. If a person reaches adulthood (let's say 18 years old male) with a healthy 15% body fat (at 200 pounds body weight) and a total body fat mass of 30 pounds, how can you explain how he reached a body weight of 400 pounds at age 40 with the same number of fat cells???!!!

He's gone from 30 pounds of fat mass to 210 pounds of fat mass, seven times more. If at age 18 his normal fat cells were 0.5 - 0.6 micrograms, the most his fat cells could handle would be another 25 pounds of fat. Obviously he increased his fat cell number over the years to the point that at age 40 he has seven times more fat cells than he did at age 18.

We know (from this study) that Ghrelin increases the number of fat cells via receptors in fat cells by inducing the proliferation and differentiation of adipocytes (fat cells) and inhibiting apoptosis (programed cell death/self-destruction) of adipocytes.

Also the simultaneous combination of the hormones insulin and cortisol causes an increase in the number of fat cells. The following descriptions are taken from two studies of fat cells in-vitro (in a test tube), as opposed to in-vivo (live subjects):
In this study, a thirty- to seventy fold increase in the number of developing fat cells was achieved by the addition of cortisol or related corticosteroids in the presence of insulin. Either of the two hormones alone was ineffective.
And in this study, acute amplification of adipose (fat cell) conversion (multiplication) was observed mainly when glucocorticoids (cortisol) and insulin were added simultaneously. Morphological quantification of lipid-containing cells confirmed acceleration of the maturation process.

It could be that what I'm saying is not conventional, and not what's taught in dietetics classes, but not only have I made a strong case proving that total fat cell number can be increased or decreased, but this is really crucial to work on for those who want to attain long term fat loss. Unfortunately the mainstream university courses have totally missed this.

[Robert Santana]

Thanks for responding Robert. The article you linked to looks very interesting, but I can't access the full article without paying $20. If I understood the summary correctly, it is claiming that the total number of fat cells doesn't change after reaching adulthood. And that makes no sense to me. The average size (weight) of an adult fat cell is about 0.6 micrograms, but they can vary in size from 0.2 micrograms to 0.9 micrograms. If a person reaches adulthood (let's say 18 years old male) with a healthy 15% body fat (at 200 pounds body weight) and a total body fat mass of 30 pounds, how can you explain how he reached a body weight of 400 pounds at age 40 with the same number of fat cells???!!!

He's gone from 30 pounds of fat mass to 210 pounds of fat mass, seven times more. If at age 18 his normal fat cells were 0.5 - 0.6 micrograms, the most his fat cells could handle would be another 25 pounds of fat. Obviously he increased his fat cell number over the years to the point that at age 40 he has seven times more fat cells than he did at age 18.

We know (from this study) that Ghrelin increases the number of fat cells via receptors in fat cells by inducing the proliferation and differentiation of adipocytes (fat cells) and inhibiting apoptosis (programed cell death/self-destruction) of adipocytes.

Also the simultaneous combination of the hormones insulin and cortisol causes an increase in the number of fat cells. The following descriptions are taken from two studies of fat cells in-vitro (in a test tube), as opposed to in-vivo (live subjects):
In this study, a thirty- to seventy fold increase in the number of developing fat cells was achieved by the addition of cortisol or related corticosteroids in the presence of insulin. Either of the two hormones alone was ineffective.
And in this study, acute amplification of adipose (fat cell) conversion (multiplication) was observed mainly when glucocorticoids (cortisol) and insulin were added simultaneously. Morphological quantification of lipid-containing cells confirmed acceleration of the maturation process.

It could be that what I'm saying is not conventional, and not what's taught in dietetics classes, but not only have I made a strong case proving that total fat cell number can be increased or decreased, but this is really crucial to work on for those who want to attain long term fat loss. Unfortunately the mainstream university courses have totally missed this.

Thanks for responding. The article I linked discusses what some of what you addressed. I cannot share it here for obvious reasons but if you can get a hold of it from someone it is a useful article. One quote I will share is:

"Analysis of adipocyte turnover using carbon-14 dating (for a detailed methodological description, see Ref. [5]), however, has recently shown that this is not the case, but rather that adipocytes are a dynamic and highly regulated population of cells. New adipocytes form constantly to replace lost adipocytes, such that approximately every 8 years 50% of adipocytes in the human subcutaneous fat mass are replaced [1]."

and

"Necrotic and apoptotic adipocytes are also found in adult human white adipose tissue [11], even though no decrease in adipocyte number is seen with age. Together these data suggest that pre-adipocytes are recruited to become lipid-filled mature adipocytes at the same rate that adipocytes die, and that in this way the fat mass is in constant flux, and adipocyte number is kept constant."

In response to your question regarding the 400 lb individual, this goes back to a major point of my discussion. The male you are describing is less likely to get to 400 lbs if those are his metrics at that age. Its the male who is 30-40% body fat at age 18 who is more likely to get to 400 lbs when he is older because he has a greater number of fat cells. There are humans that walk around at low body fat regardless of what they eat and humans who can get up to 400-600 lbs by "looking at food." The running theory is that these individuals who get to extremes of morbid obesity accumulate a higher number of fat cells in youth and then those fat cells expand in adulthood because hyperplastic obesity is strongly associated with early onset obesity . In other words, class III obese children and adolescents are more likely to get to extremes of body weight as adults because that phenotype typically carries more fat cells. Unfortunately I cannot view the study you linked at this time so I can't comment much on the methodology beyond the fact that in vitro studies and rodent models do not fully predict the response that may occur in a living human.

Ultimately, there is much we don't know and there are many unanswered questions and neither I nor you know the real answer here otherwise we would have a Nobel Prize. What we do know is that based on the critical fat cell size hypothesis, the achievement of a specific mean fat cell size induces a subsequent increase in fat cell number. The extent at which this occurs in humans is unknown and we definitely need long term studies to conclude this. Ultimately, it is impossible to conclude whether the average increase in fat cell number seen in obese and severely obese individuals is the result of adult adipocyte recruitment or rather a reflection of a predisposition, by their pre-adulthood fat cell number, to be become obese/severely obese. The latter is supported by short-term studies in adult humans that do not show increases in fat cell number following significant weight gain. On the other side of the spectrum, human studies on weight loss, both voluntary and involuntary, have reported no reduction in fat cell number despite a dramatic reduction in fat cell size. So there is something definitely going on there but again, lots of variables, lots that we can't measure, and lots of unanswered questions.

To be clear, this is what we currently know as is what you've shared. The hope is that we continue to accumulate more information on this topic so that we can better understand how to treat it, if indeed it needs to be treated. Keep in mind what we discussed above about sumo wrestlers. When you control for exercise, many of the negative health effects associated with obesity are blunted, which brings us back to the main point of this presentation. Is the fat really the issue we want to address or the physical inactivity? No right or wrong answer there but certainly evidence to support either direction.

[Yonason Herschlag]

Thanks for responding. The article I linked discusses what some of what you addressed. I cannot share it here for obvious reasons but if you can get a hold of it from someone it is a useful article. One quote I will share is:

"Analysis of adipocyte turnover using carbon-14 dating (for a detailed methodological description, see Ref. [5]), however, has recently shown that this is not the case, but rather that adipocytes are a dynamic and highly regulated population of cells. New adipocytes form constantly to replace lost adipocytes, such that approximately every 8 years 50% of adipocytes in the human subcutaneous fat mass are replaced [1]."

and

"Necrotic and apoptotic adipocytes are also found in adult human white adipose tissue [11], even though no decrease in adipocyte number is seen with age. Together these data suggest that pre-adipocytes are recruited to become lipid-filled mature adipocytes at the same rate that adipocytes die, and that in this way the fat mass is in constant flux, and adipocyte number is kept constant."

In response to your question regarding the 400 lb individual, this goes back to a major point of my discussion. The male you are describing is less likely to get to 400 lbs if those are his metrics at that age. Its the male who is 30-40% body fat at age 18 who is more likely to get to 400 lbs when he is older because he has a greater number of fat cells. There are humans that walk around at low body fat regardless of what they eat and humans who can get up to 400-600 lbs by "looking at food." The running theory is that these individuals who get to extremes of morbid obesity accumulate a higher number of fat cells in youth and then those fat cells expand in adulthood because hyperplastic obesity is strongly associated with early onset obesity . In other words, class III obese children and adolescents are more likely to get to extremes of body weight as adults because that phenotype typically carries more fat cells. Unfortunately I cannot view the study you linked at this time so I can't comment much on the methodology beyond the fact that in vitro studies and rodent models do not fully predict the response that may occur in a living human.

Ultimately, there is much we don't know and there are many unanswered questions and neither I nor you know the real answer here otherwise we would have a Nobel Prize. What we do know is that based on the critical fat cell size hypothesis, the achievement of a specific mean fat cell size induces a subsequent increase in fat cell number. The extent at which this occurs in humans is unknown and we definitely need long term studies to conclude this. Ultimately, it is impossible to conclude whether the average increase in fat cell number seen in obese and severely obese individuals is the result of adult adipocyte recruitment or rather a reflection of a predisposition, by their pre-adulthood fat cell number, to be become obese/severely obese. The latter is supported by short-term studies in adult humans that do not show increases in fat cell number following significant weight gain. On the other side of the spectrum, human studies on weight loss, both voluntary and involuntary, have reported no reduction in fat cell number despite a dramatic reduction in fat cell size. So there is something definitely going on there but again, lots of variables, lots that we can't measure, and lots of unanswered questions.

To be clear, this is what we currently know as is what you've shared. The hope is that we continue to accumulate more information on this topic so that we can better understand how to treat it, if indeed it needs to be treated. Keep in mind what we discussed above about sumo wrestlers. When you control for exercise, many of the negative health effects associated with obesity are blunted, which brings us back to the main point of this presentation. Is the fat really the issue we want to address or the physical inactivity? No right or wrong answer there but certainly evidence to support either direction.

A well written response. Thanks for giving me the time and effort to respond so respectfully.

To sum up our exchange so far for the less scientific readers, you are taking the mainstream position that is commonly taught today, that the number of fat cells in a person doesn't change much after reaching adulthood, and that added fat mass accumulated with age is primarily an expansion of those fat cells. Whereas I am taking a position challenging this theory saying that not only can the number of fat cells significantly increase, but they can also be decreased... and for the purpose of long term fat loss it is incumbent to strive to reduce fat cell number as much as possible.

I will add, that the reason we need to reduce fat cell number to attain long term fat loss is because fat cells send signals to the hypothalmus via the hormone leptin to direct metabolism to maintain homeostasis of the size of the fat cells. In other words if a person loses fat mass but retains the same number of fat cells, those cells will feel deprived, and get that message to the brain to change metabolism in order to get them filled up with fat mass to their homeostatic level.

What we agree on, is that as you have stated, a person who reaches adulthood as obese will more likely reach middle age as morbidly obese than a person who reached adulthood as normal. Nevertheless, no matter how you dice it, whether a person reaches adulthood slim or fat, we witness in either case that it is very common to reach middle age MUCH fatter than one was just entering adulthood. And the point I am trying to stress is that there is a limit in how much fat cells can stretch. Fat cell stretching simply can not account for more than doubling one's fat mass. Agreed, the case in my previous post citing a person who increased his fat mass by seven times is uncommon, but tripling or quadrupling one's fat mass by middle age is all to common to sweep under the table attributing to fat cells merely stretching.

So despite being a layman (as opposed to a person of scientific background) I am confident in my reasoning abilities to say that without a doubt fat cell number changes significantly after reaching adulthood.

In response to a good point you made in agreement with me "What we do know is that based on the critical fat cell size hypothesis, the achievement of a specific mean fat cell size induces a subsequent increase in fat cell number." In other words, you agree, that if one gets so fat as to stretch their fat cell to their limits, that will spur the body to increase fat cell number to accommodate the higher fat mass. I will add to that an argument that in the same way, if one's fat cells are starved long enough (at least a year - the more the merrier), under the right conditions one can reduce one's number of fat cells. I do not have proof of this argument, as you say studies are lacking, but I do have some evidence. And that is the case studies of people who go through by-pass surgery:

A mega-analysis of sixteen studies of 492 subjects shows that the typical 310-pound subject (height 5’7”; BMI 50) will reach a weight as low as 175 pounds at the two-year mark after surgery (a loss of 77% of excess body weight; BMI 27.4). Then the weight will gradually begin the climb up, such that seven to eight years after surgery he or she is up to 235 pounds (BMI 37).
In review, the typical BMI changes from:
50 before the operation, to
27.4 two years after the operation, to
37 seven years after.

My argument is that would the number of fat cells have remained the same, the forces of homeostasis would bring the subjects back up to their original weight. I am saying that because they successfully starve their fat cells for several years, the number of fat cells must over time become reduced enabling the lower level of fat mass to become semi permanent.

[Robert Santana]

A well written response. Thanks for giving me the time and effort to respond so respectfully.

To sum up our exchange so far for the less scientific readers, you are taking the mainstream position that is commonly taught today, that the number of fat cells in a person doesn't change much after reaching adulthood, and that added fat mass accumulated with age is primarily an expansion of those fat cells. Whereas I am taking a position challenging this theory saying that not only can the number of fat cells significantly increase, but they can also be decreased... and for the purpose of long term fat loss it is incumbent to strive to reduce fat cell number as much as possible.

I will add, that the reason we need to reduce fat cell number to attain long term fat loss is because fat cells send signals to the hypothalmus via the hormone leptin to direct metabolism to maintain homeostasis of the size of the fat cells. In other words if a person loses fat mass but retains the same number of fat cells, those cells will feel deprived, and get that message to the brain to change metabolism in order to get them filled up with fat mass to their homeostatic level.

What we agree on, is that as you have stated, a person who reaches adulthood as obese will more likely reach middle age as morbidly obese than a person who reached adulthood as normal. Nevertheless, no matter how you dice it, whether a person reaches adulthood slim or fat, we witness in either case that it is very common to reach middle age MUCH fatter than one was just entering adulthood. And the point I am trying to stress is that there is a limit in how much fat cells can stretch. Fat cell stretching simply can not account for more than doubling one's fat mass. Agreed, the case in my previous post citing a person who increased his fat mass by seven times is uncommon, but tripling or quadrupling one's fat mass by middle age is all to common to sweep under the table attributing to fat cells merely stretching.

So despite being a layman (as opposed to a person of scientific background) I am confident in my reasoning abilities to say that without a doubt fat cell number changes significantly after reaching adulthood.

In response to a good point you made in agreement with me "What we do know is that based on the critical fat cell size hypothesis, the achievement of a specific mean fat cell size induces a subsequent increase in fat cell number." In other words, you agree, that if one gets so fat as to stretch their fat cell to their limits, that will spur the body to increase fat cell number to accommodate the higher fat mass. I will add to that an argument that in the same way, if one's fat cells are starved long enough (at least a year - the more the merrier), under the right conditions one can reduce one's number of fat cells. I do not have proof of this argument, as you say studies are lacking, but I do have some evidence. And that is the case studies of people who go through by-pass surgery:

A mega-analysis of sixteen studies of 492 subjects shows that the typical 310-pound subject (height 5’7”; BMI 50) will reach a weight as low as 175 pounds at the two-year mark after surgery (a loss of 77% of excess body weight; BMI 27.4). Then the weight will gradually begin the climb up, such that seven to eight years after surgery he or she is up to 235 pounds (BMI 37).
In review, the typical BMI changes from:
50 before the operation, to
27.4 two years after the operation, to
37 seven years after.

My argument is that would the number of fat cells have remained the same, the forces of homeostasis would bring the subjects back up to their original weight. I am saying that because they successfully starve their fat cells for several years, the number of fat cells must over time become reduced enabling the lower level of fat mass to become semi permanent.

Thanks for sharing. So let me rephrase my point because I think it is being missed.

1) Fat cell number does increase and may happen in adulthood but we do not know for sure because studies have shown that in periods of extreme weight gain in adult humans fat cell number doesn't change despite an increase in fat cell volume. This is not the same thing as saying it doesn't happen and there is good reason to believe that it may happen. I'm stating that we do not know for sure.

2) Fat cell number does decrease as a function of fat cell turnover. As new cells die, new cells are created, simple biology there. So yes technically they do decrease. What I have been saying is that it has not been observerd to occur during periods of both involuntary and voluntary weight loss in humans. What you are citing may serve as a foundation for a hypothesis but these studies are not measuring fat cell number so stating that it was reduced is currently speculative. Again, I'm not arguing that it doesn't happen, I'm stating that it has not been observed.

3) Reducing fat cell number may not improve cardiometabolic health outcomes as much as reducing fat cell size. This is because when fat cell size reaches its limit, the cells become hypoxic, which leads to a release of cytokines, which then leads to an inflammatory response, which can then lead to endothelial dysfunction, insulin resistance, diabetes, and CVD. This is why we have individuals who are "healthy obese" and show no risk for cardiometabolic disease. High number, not necessarily a high volume.

Again, the take away here, as well as in my presentation, is that "treating obesity" may not always be the solution. In several meta analyses on long-term weight loss, the vast majority of the individuals that lose weight end up gaining it all back and sometimes more. The rationale for "treating obesity" is because it is associated with a higher risk of cardiometaoblic diseases. The paradox is that weight cycling is also associated with a higher risk of cardiometabolic diseases. However, when you control for fitness, the risk associated with obesity essentially disappears, which begs the question of whether losing weight or addressing the physical inactivity is the better route to take. What I am trying to find out is if we can observe a similar effect with barbell training, hence why I'm gearing my own research in this direction and why I gave this presentation. Hope this clears it all up and if you decide to pursue a career in adipose tissue cellularity research please let us know what you find!

[Yonason Herschlag]

studies have shown that in periods of extreme weight gain in adult humans fat cell number doesn't change despite an increase in fat cell volume.

I haven't seen those studies, but I'd bet that those studies are short term (no more than a year or two at most). That is because the process of gaining fat cells is VERY slow. Perhaps the highest speed of change in fat cell # (gaining or losing) is 5-8% per year. In contrast, a person can add or lose 30 or even more pounds of fat in a year, increasing or decreasing their fat mass by 100% in that short time.

When I was 18, I had the body type of Bruce Lee - thin, muscular, and really cut (at about 145 pounds 5'9"). I probably had only ten pounds of fat at that age. It was only after age 28 that I started gaining weight. By age 49, I weighed 216, with an estimated 66 pounds of fat (a total gain of 71 pounds - 56 fat, and 15 muscle). There is absolutely no way that I increased my fat mass by nearly seven times while maintaining the same number of fat cells. Fat cells simply can't stretch that much. They can accommodate a doubling of fat mass at most.

So when you claim a study shows that fat cell number doesn't change in periods of extreme weight gain, I am certain that the study is talking about an extreme weight gain of 100% increase in fat mass in the time span of one year, with a mere negligible 5% increase in fat cell number. The point being, that if a study were conducted long term comparing twenty year olds to fifty year olds, it would be obvious that after 20-30 years of negligible 5% increases in fat cell number, that adds up after two or three decades to a very significant doubling or tripling of fat cell number.

when fat cell size reaches its limit, the cells become hypoxic, which leads to a release of cytokines, which then leads to an inflammatory response, which can then lead to endothelial dysfunction, insulin resistance, diabetes, and CVD.

Very interesting. So if a person has been gorging himself, stretching his fat cells to their very limit, he's harming his health and needs to cut calorie intake a bit to improve his health.

I'm sure you would know better than me, as you are a dietitian, but I think most yoyo dieters struggle more with keeping lost weight off permanently (due to too many empty fat cells begging the hypothalamus to fill them up), than they do with avoiding stretching their fat cells to the limit.

The rationale for "treating obesity" is because it is associated with a higher risk of cardiometaoblic diseases. The paradox is that weight cycling is also associated with a higher risk of cardiometabolic diseases. However, when you control for fitness, the risk associated with obesity essentially disappears, which begs the question of whether losing weight or addressing the physical inactivity is the better route to take.

At age 49 I started weightlifting. I'm now 53. I went from deadlifting 130kg to 210 kg, and from partially squatting 80 kg to squatting to parallel 160 kg, and from benching 80kg to benching 110 kg(X5) (my progress in benching was held back due to tendonitis). My body weight went from 216 to 230, with a fat mass loss of an estimated 9 pounds, and an estimated added muscle mass of 23 pounds.

I am with you in that I am not interested in yoyo dieting, and weightlifting has surely improved my health (and of course strength). But despite my better health from weightlifting, I am still in dire need of reducing body fat (as most people are).

I am also with you 100% that most people need to get up off their rear ends and start lifting weights. But after four years of lifting quite intensely, at age 53 I can tell you that just lifting weights is not sufficient for attaining ideal health. I'm sure as a dietitian you agree with this. And in all due respect to Mark Rippetoe, I think that aerobics can at times for some people be no less crucial for attaining ideal health than weightlifting. Of course proper nutrition and meal timing are also crucial.