Why body not keep excess Triglycerides into adipose but keep it in blodd

[Eliada]

Hi, 

 

I'm new to this forums, please accept my apologies first I'm asking on the wrong forum.

(Some context, I'm not a student / professional on biology / physiology, I'm a IT guy but start getting interest in physiology / health knowledge. I don't satisfy with very general health related suggestion but wondering why. On the other hand, I'm not equipped with knowledge to comprehend the technical literature / papers. Sometimes I struggle to find the information on which is slight more detail than general health focused website).

 

When I try to understand "High Blood Fat" problem, most articles just explain high blood fat is either caused by genetic problem or bad diet.

But I'm trying to understand a little bit deeper on why.

 

As I know, when we digest fat, the digestive process will convert it into triglycerides, which will carry through the blood stream by lipoprotein. It should eventually stored in adipose tissue.

So, if I eat too much fat, then, the natural result should be storing excess body fat in forms of adipose tissue. How does it ends up in the form of high level of triglycerides in the blood?

 

 

Edited January 26, 2020 by Eliada

[guidoLamoto]

https://en.m.wikipedia.org/wiki/Lipogenesis Probably more than you want to know. In a nutshell: fat metabolism is controlled mainly by insulin interacting with several other hormones and transcription factors to regulate the genes responsible for making or using triglycerides. (The evidence that high triglyceride levels are correlated with arteriosclerosis is pretty flimsy.)

Eating fat doesn't make you as fat as eating an equal amount of calories in carbs-- Carbs stimulate more insulin secretion which sets off the enzyme cascade to store more fat and to burn less fat.

A simplistic explanation on the evolutionary value of such a system: our ancestors roaming the hot areas of east Africa where we evolved, would do better if they stored less highly insulating fat, so when times were good and game (hi fat source) was plentiful, they could switch off their fat-saving genes. When hunting was bad and they were forced to eat weeds ( hi carb source), they had a better chance of surviving until their next good meal (meat) became available if they would switch on the fat saving genes. It appears insulin is the chemical signal for this.

Blood levels of triglycerides are defined only after an 18 hr fast. Triglyds can be high after eating a fatty meal (up to a couple hundred mg%) and are meaningless. For high levels after an 18 hr fast, there is essentially no evidence that it correlates at all with arteriosclerosis in men, and only a very weak pos. corr. for older women...There's also the genetic condition of Familial Hypertriglyceridemia where levels are in excess of a couple thousand mg%. Those people have a slightly elevated risk of heart disease, but a very high risk for pancreatitis.

Cholesterol levels are an entirely different matter, controlled almost exclusively by genetics, not diet. Critical analysis of the data shows that, in fact, only those with HDL (the good stuff; H for Happy) levels below 25mg% are at significant risk of early heart disease....and LDL (the bad stuff; L for Lousy) correlate rather poorly with risk.

This whole concept of diet and arteriosclerosis is complicated by pharmaceutical profit motives and malpractice risks. It's  generally not publicized that the benefits of regular exercise completely offset the negative risks of hi chol levels, or that  higher levels of carnitine and CLAs in the diet (only found in meat) are highly correlated with improved risks.

Best advice: do what your mother always told you-- eat everything in moderation. Maintain a normal body weight and exercise regularly. The rest is in your genes and you can't change that.

[Strange]

18 minutes ago, guidoLamoto said:

Cholesterol levels are an entirely different matter, controlled almost exclusively by genetics, not diet.

Harvard University would appear to disagree:

Quote

The biggest influence on blood cholesterol level is the mix of fats and carbohydrates in your diet—not the amount of cholesterol you eat from food.

https://www.hsph.harvard.edu/nutritionsource/what-should-you-eat/fats-and-cholesterol/cholesterol/

[guidoLamoto]

a) Better read the article you just quoted.

b) https://health.clevelandclinic.org/why-you-should-no-longer-worry-about-cholesterol-in-food/

Plenty of articles in the research literature showing low carb diets lower chol levels better than low fat diets BUT-- neither lowers chol levels enough to move you from a higher risk category to a lower risk category, ie-- no practical benefit. Some diets, like the low fat diets, can lower LDL a little, but also lower HDL levels too-- theoretically increasing your risk profile.

BTW- there was a statistical analysis of the chol research lit about 30 y/a-- it found that  those with chol level of 200 lived only an average of 4 days longer than those with chol of 300. (!!) BFD.

Edited February 9, 2020 by guidoLamoto

[Strange]

2 minutes ago, guidoLamoto said:

a) Better read the article you just quoted.

I did.

3 minutes ago, guidoLamoto said:

b) https://health.clevelandclinic.org/why-you-should-no-longer-worry-about-cholesterol-in-food/

Maybe you are confused by the fact that dietary cholesterol has little effect (which has been known for a long time) but diet does.

 

[guidoLamoto]

5 minutes ago, Strange said:

I did.

Maybe you are confused by the fact that dietary cholesterol has little effect (which has been known for a long time) but diet does.

 

Maybe you're confused about the difference between statistical significance and clinical significance. Dietary studies typically show changes of chol  of only 10-20 mg%- - that won't change your risk category. ...LDL levels have only a correlation coefficient vs MI of 0.3 --not all that great as a predictor. At least the LDL/HDL ratio has a coeff. of 0.5-- better, but I still wouldn't bet on any given pt's future based on that.

BTW- statins have a really miserable success rate in preventing 2nd MIs (no effect at all in preventing 1st MI)- The Need To Treat number is 45-- you gotta treat 45 pts with statins to prevent one additional, 2nd MI. Even that "improvement" is better explained by the anti-inflammatory & anti-coagulant effects of the drug. In the few head to head comparisons of the various statins, outcomes were not correlated at all to chol lowering effects.

[Strange]

1 minute ago, guidoLamoto said:

Maybe you're confused about the difference between statistical significance and clinical significance. Dietary studies typically show changes of chol  of only 10-20 mg%- - that won't change your risk category. ...LDL levels have only a correlation coefficient vs MI of 0.3 --not all that great as a predictor. At least the LDL/HDL ratio has a coeff. of 0.5-- better, but I still wouldn't bet on any given pt's future based on that.

You are very fond of referencing "studies". For all I know you have made these numbers up. (I'm sure you haven't. But, on the other hand, you haven't given any sources.)

[studiot]

4 minutes ago, guidoLamoto said:

Maybe you're confused about the difference between statistical significance and clinical significance.

Well I certainly am confused.

Perhaps you would be so kind as to explain it to me.

[Strange]

10 minutes ago, guidoLamoto said:

Maybe you're confused about the difference between statistical significance and clinical significance.

As I never mentioned either (and neither did you, before now), I'm not sure why you would think that.

[guidoLamoto]

2 minutes ago, studiot said:

Well I certainly am confused.

Perhaps you would be so kind as to explain it to me.

Gladly.

Statistical significance  is a mathematical treatment of test results that gives us an idea of how much we should trust the results. Eg- we treat 100 pts with drug A and 100 pts with drug B. After the trial, we find that 80 pts taking A survived and, say, 0nly 40 pts on B survived. After the math is done, we find that the difference is "significant at p =0.05 level" Ie- we''d get similar results if we repeated the test  in 95% of the trials. I'd certainly want to be given drug A if I had that disease.

OTOH- let's say the results were 80 for A and 78 for B, but the statistical analysis still said it's significant at the p = .05 level. We may make the value judgement that that's not clinically significant....If A cost 10x more than B, we'd probably have no reservations about using drug B.

In the matter of diet & chol, they may have easily shown that a change of 10mg% is statistically significant, but risk categories are based on changes of 50 -100mg% so 10  is of no consequence-- clinically insignificant, ie - of no practical value.

Remember that if statisticians torture the numbers long enough, they can get them to confess to anything.

[studiot]

7 minutes ago, guidoLamoto said:

OTOH- let's say the results were 80 for A and 78 for B, but the statistical analysis still said it's significant at the p = .05 level. We may make the value judgement that that's not clinically significant....If A cost 10x more than B, we'd probably have no reservations about using drug B.

 

Is 78 out of 100 statistically different from 80 out of 100 at the stated level?

[guidoLamoto]

I was just making up numbers for the sake of the illustration. If we really applied Student's t-test, I rather doubt the 80/78  result would prove to be significant-- it'd be pretty likely a difference of 2 out of 80 would be random variation. Maybe I should have used as example a study of a drug vs placebo-- and a  70/80 result would mean the drug works but not much better than nothing, while the 80/40 result would mean it was worth taking.....The real point is that sometimes statistically significant results are represented by numbers so small that they don't make any practical difference.

 

[studiot]

11 minutes ago, guidoLamoto said:

The real point is that sometimes statistically significant results are represented by numbers so small that they don't make any practical difference.

 

 

I am asking if that is consistent with their null hypothesis or a failure to establish a proper null hypothesis?

[CharonY]

2 hours ago, guidoLamoto said:

Cholesterol levels are an entirely different matter, controlled almost exclusively by genetics,

So rather trivially that is very unlikely to be true. Metabolites are regulated by a complex interplay of genetic and non-genetic factors. What is true is that the role of specifically dietary cholesterol has been revised significantly. I.e. the simple assumption that high dietary cholesterol intake translates directly in high blood values, does not hold true. However, it is not clear why. Some studies suggest that dietary cholesterol can modulate the de novo synthesis of cholesterol, whereas others point to components other than cholesterol in the diet.

The genetic factors are also not well understood, either. Some variations of apolipoprotein genes, for example have been shown involved in clearance, and mutations appear to increase variability of LDL cholesterol levels. There are a couple of GWAS studies showing certain loci potentially involved in lower blood cholesterol levels, but with unknown mechanism. As a whole the genetic factors are poorly understood and there is little evidence indicating that genetic factors would even the major determinant of blood cholesterol level (though they will certainly play a modulating factor, with all else being the same, which would be a highly artificial situation, of course).

[guidoLamoto]

10 hours ago, studiot said:

 

I am asking if that is consistent with their null hypothesis or a failure to establish a proper null hypothesis?

I'm saying there's a difference between establishing that the results of a study are scientifically  valid vs establishing that they're useful in practical matters.

Another example: suppose we test using a regulation baseball bat vs a corked bat. Let's say we find that the corked bat consistently adds 5 feet to the flight of a fly ball...In a game situation, how many flies fall 5 ft short of the fence?..and for a fly ball that would have gone over the fence with a reg bat, anyway, the extra 5 ft from the corked bat is still a home run-- no extra credit for how far into the stands it goes.

(For you physics purists, I admit this is a disingenuous argument. -- it has been studied and the ball actually goes farther with the reg bat. Hitting a ball is essentially an elastic impulse and represents conservation of momentum, not addition of force...The increase in bat speed attained by corking is more than offset by the loss of mass. "The Physics of Baseball" is an interesting read.)

11 hours ago, CharonY said:

So rather trivially that is very unlikely to be true. Metabolites are regulated by a complex interplay of genetic and non-genetic factors. What is true is that the role of specifically dietary cholesterol has been revised significantly. I.e. the simple assumption that high dietary cholesterol intake translates directly in high blood values, does not hold true. However, it is not clear why. Some studies suggest that dietary cholesterol can modulate the de novo synthesis of cholesterol, whereas others point to components other than cholesterol in the diet.

The genetic factors are also not well understood, either. Some variations of apolipoprotein genes, for example have been shown involved in clearance, and mutations appear to increase variability of LDL cholesterol levels. There are a couple of GWAS studies showing certain loci potentially involved in lower blood cholesterol levels, but with unknown mechanism. As a whole the genetic factors are poorly understood and there is little evidence indicating that genetic factors would even the major determinant of blood cholesterol level (though they will certainly play a modulating factor, with all else being the same, which would be a highly artificial situation, of course).

The cholesterol molecules measured in your blood are not the cholesterol molecules you ate. The cells (mostly in the liver) manufacture cholesterol using the basic building block Ac-CoA derived from the carbs, fats & protein in your diet. Cholesterol itself is essentially a raw material used as the basis for the steroid hormones and is found in the blood en route to the assembly lines that will use it in the various glands.....How much chol the liver dumps into the blood depends mostly on the genetics of chol synthesis, but also, of course, on the availability of raw material--- just like two different auto assembly lines will produce cars at  rates determined mostly by the way the lines are set up and manned, but also on how much raw material each has to work with. Union rules  and company incentives (enzyme inhibitors & stimulators) may also regulate production rates.

The studies done on diet vs chol usually show only small changes in chol levels over the first several weeks to months, with return towards previous levels after 6  months of the continuing diet. ...You'd expect that if it was in fact a self-regulating system. ...It's not nice to mess with MotherNature

 

 

[CharonY]

4 hours ago, guidoLamoto said:

he cholesterol molecules measured in your blood are not the cholesterol molecules you ate.

That is what I meant with dietary cholesterol vs de novo synthesized cholesterol. As mentioned there is some data suggesting modulation of de novo synthesis, but the connection is unclear.

There is more data out there suggesting that lifestyle changes (such as exercise) as well as diet (but, as mentioned, not necessarily related to cholesterol intake) can alter cholesterol levels, but I am unaware of the fact that most of these effects are transient, perhaps you could point me towards the lit? Effects on diet on health are notoriously difficult to establish.

4 hours ago, guidoLamoto said:

How much chol the liver dumps into the blood depends mostly on the genetics of chol synthesis, but also, of course, on the availability of raw material--

That is partially why I said that metabolism cannot be solely dependent on genetics. In addition to the availability of metabolites and its precursors, such as signaling pathways that react to a large number of other external and internal cues play a role (e.g. along the steroid axis you mentioned).  Stress, lack of sleep, physical exercise (or lack thereof) etc. can significantly alter metabolism on many levels. As such I consider the previous claim that all is just genetic to be an extraordinary claim.

[studiot]

4 hours ago, guidoLamoto said:

I'm saying there's a difference between establishing that the results of a study are scientifically  valid vs establishing that they're useful in practical matters.

Yes I understand what you are saying.

But I wish to challenge that since in my view the purpose of the scientific (have we changed from statistical ?) analysis is to establish a measurable confidence interval within which any result can be accepted and outside which any result can be rejected. The two purposes are inextricably linked. Your bat example demonstrates that exactly, in basing the decision to choose bat A on test results, however scanty.

54 minutes ago, CharonY said:

As such I consider the previous claim that all is just genetic to be an extraordinary claim.

 

I think this was just over broad brush treatment and guido was correct in distinguishing sources of cholesterol.

 

Coincidentally I am following a course in Phsychology at the moment and the last session was all about eating disorders and obesity.
That medical studies indicate that little or no correlation between overweight conditions and cholesterol levels was brought up and discussed.

 

[CharonY]

4 minutes ago, studiot said:

Coincidentally I am following a course in Phsychology at the moment and the last session was all about eating disorders and obesity.
That medical studies indicate that little or no correlation between overweight conditions and cholesterol levels was brought up and discussed.

So there is actually some interesting data out there trying to look at this issue. One big problem is that body weight is a composite result of many different factors. In addition, high calorie intake can often be associated with a variety of other lifestyle factors that may affect health outcome differently. For example, folks following a low carbon diet have been shown to decrease body weight, but LDL and HDL-cholesterol levels were elevated. In retrospective studies certain folks with high body weight, low exercise and high carbon diet often (but not always consistently) showed higher cholesterol levels. Some studies suggest a stronger association in youths, as obesity there indicates presence of higher levels of risk factors.

[Dagl1]

18 hours ago, guidoLamoto said:

Eating fat doesn't make you as fat as eating an equal amount of calories in carbs-- Carbs stimulate more insulin secretion which sets off the enzyme cascade to store more fat and to burn less fat.

Do you mean that eating an equal amount of calories of fat or carbs will lead to different fat levels, all things being equal?
Over the long term, if the same amount of calories are eaten (or well, one should find out the efficiency by which the person absorbs carbs and fat and then normalise using that) and the same amount of energy is used up, one would be exactly equally as fat right? Preferably this is not tested in full-fat or full-carb diets, but where only some % of the total calorie intake is changed so that it still remains a sort of balanced diet (carb vs fat wise).
If everything stays equal and their basal metabolism doesn't increase, and they absorb the same amount of calories, then it shouldn't matter what the calories come from. And in the end fat is stored calories, the amount of fat should remain the same over the long term

Edit: I did just realise that of course, there may be some differences in the efficiency of breakdown of fat and carbs, additionally, I believe (but could be wrong, can't find my notes on fat metabolism at the moment) that storing carbs in the form of fat is a net energy loss (as it requires some energy to 'convert' the carbs to fat), so that could also affect the long term fat quantities (when comparing fat vs carbs in diet).

@CharonY Do you know if slowing down or quickening of basal metabolism is possible when absorbing a higher percentage of fats than carbs or vice versa (while everything else remains equal)?

-Dagl

[CharonY]

22 hours ago, Dagl1 said:

Do you know if slowing down or quickening of basal metabolism is possible when absorbing a higher percentage of fats than carbs or vice versa (while everything else remains equal)?

Regulation of basal metabolism is fairly complex and from what I have seen also poorly understood. In addition, most nutritional studies do not provide mechanistic insights. Roughly speaking, there are factors that, depending on the study, might indicate changes in  metabolic rates, but the relationship remain complex. Changes in body mass, for example can change metabolic rate, as well as calorie restriction. The latter is connected to an effect you might be thinking about, called postprandial thermogenesis which reflects the short-term increase of metabolic rate related with the type of food composition (highest if high in protein, lowest if high on fats). However, the actual net effect is difficult to assess because it is also dependent on the amount as well as the precise type of metabolite ingested,  as well as a whole range of characteristics of the subjects  (e.g. age, exercise, nutritional status etc.). So while we know that the basal metabolism shifts depending on food composition, the overall net effect on weight is going to be highly dependent on the individual with quite some contradicting results in the lit.

 

[guidoLamoto]

On ‎2‎/‎11‎/‎2020 at 3:54 PM, CharonY said:

Regulation of basal metabolism is fairly complex and from what I have seen also poorly understood. In addition, most nutritional studies do not provide mechanistic insights. Roughly speaking, there are factors that, depending on the study, might indicate changes in  metabolic rates, but the relationship remain complex. Changes in body mass, for example can change metabolic rate, as well as calorie restriction. The latter is connected to an effect you might be thinking about, called postprandial thermogenesis which reflects the short-term increase of metabolic rate related with the type of food composition (highest if high in protein, lowest if high on fats). However, the actual net effect is difficult to assess because it is also dependent on the amount as well as the precise type of metabolite ingested,  as well as a whole range of characteristics of the subjects  (e.g. age, exercise, nutritional status etc.). So while we know that the basal metabolism shifts depending on food composition, the overall net effect on weight is going to be highly dependent on the individual with quite some contradicting results in the lit.

 

You've brought up several good points in your last several posts.

Nutritional studies, thanks to those inconvenient ethics rules, won't allow us to do real controlled experiments anymore. (I'm sure this is why our prisons are so overcrowded now-- they can't volunteer as guinea pigs anymore to shorten their sentences.) Most studies rely on questionnaires and the reliability of subjects' memories: "How much smoked meat did you consume everyday from  June of1982 - Sept of1996?" as if they could remember and never changed their diets. Other studies with more closely prescribed diets are short term (that's how finding works) and often show any changes occurring over the first few months return to baseline levels after one year-- ?compensatory mechanism as you suggest?

You bring up a good point about some studies showing chol levels actually rising on low carb diets--I don't think it's been studied, but could physiological stress cause chlo levels to go up-- like wbc, sed rate, ferritin levels etc?..That would explain the small but definite risk of CAD vs chol levels---  oxidative or mechanical stress on the intima causes "cracks" which then recruit the healing response (fibrinogen-fibrin-WBCs, coagulation cascade and  chol incorporated into the "scar?"....Hi chol may be the result, not the cause of arteriosclerosis.

After 45 yrs of medical practice, I'm thoroughly convinced the leading cause of HTN is worrying about your chol level.

[CharonY]

15 minutes ago, guidoLamoto said:

physiological stress cause chlo levels to go up-- like wbc, sed rate, ferritin levels etc?..

There have been studies suggesting that stress may alter lipid metabolism, but as often, mechanisms are unclear. Similarly observations were made with exercise stress, but the effects are also somewhat complicated and not simply a matter of up and down. At minimum, it depends on the duration and type (exercise tends to stabilize or reduce, long-term stress associated with increase in cortisol, the opposite).

1 hour ago, guidoLamoto said:

Most studies rely on questionnaires and the reliability of subjects' memories:

While many are like that (though most studies ask for filling out daily diaries/questionnaires and not just general recalls), there are also some with controlled diets. But rather obviously they tend to be short term. But even then it would be virtually impossible to limit and control all other life events that may influence metabolism. And even if you could, there is a good chance that you are creating a highly artificial environment which will limit our ability infer biological mechanisms.

Quote

Hi chol may be the result, not the cause of arteriosclerosis.

I am not entirely sure how that would work, even ignoring the current hypotheses, there is only evidence for local accumulation of cholesterol and since most of it is eventually enveloped in the tissue I am not entirely sure how that could raise overall cholesterol levels.

 

As a side note, I am not sure whether you were joking, but the ability to volunteer for medical experiments has obviously virtually no impact on incarceration rates. 

[guidoLamoto]

1 hour ago, CharonY said:

There have been studies suggesting that stress may alter lipid metabolism, but as often, mechanisms are unclear. Similarly observations were made with exercise stress, but the effects are also somewhat complicated and not simply a matter of up and down. At minimum, it depends on the duration and type (exercise tends to stabilize or reduce, long-term stress associated with increase in cortisol, the opposite).

Mechanism may unclear on the details at the specific biomolecular/genetic level, but in general we can say it has to do with recruitment/inhibition of genes &/or certain enzymes. For example, Cushing's Dis (excess cortisol) pts characteristically show loss of fat stores in the limbs and increase in fat stores in the cheeks and torso (centripetal obesity & moon face). Physiol. stress increase epinephrine levels which in turn influence glucagon & insulin levels which in turn influence glucose & fat metabolism.

Quote

While many are like that (though most studies ask for filling out daily diaries/questionnaires and not just general recalls), there are also some with controlled diets. But rather obviously they tend to be short term. But even then it would be virtually impossible to limit and control all other life events that may influence metabolism. And even if you could, there is a good chance that you are creating a highly artificial environment which will limit our ability infer biological mechanisms.

I am not entirely sure how that would work, even ignoring the current hypotheses, there is only evidence for local accumulation of cholesterol and since most of it is eventually enveloped in the tissue I am not entirely sure how that could raise overall cholesterol levels.

Plaque formation is initiated by loss of integrity of the intima of the arterial vessels--( exactly analogous to "dry rot" of old rubber- oxidation disrupts the continuity/integrity of the rubber polymers. In arteries , oxidation causes denaturization of the proteins.) That initiates the conversion of fibrinogen to fibrin and the reticular structure literally traps WBCs and lipids, including chol, like fish in a net. The more chol in the blood stream, the more caught in the net, forming a thicker scar (plaque). Chol doesn't cause the injury to the artery. It's part of the healing response....Chol levels might be caused to rise by chemical signals emanating from the growing plaque. Cf- increased WBC production by bone marrow  when an abscess is present somewhere remote, or increased BS levels in response to exercise. "Acute phase reactants"- sed rate c-reactive protein, ferritin al go up in times of stress.

Physiological response to stress is generally bi-phasic: an acute response and then a more efficient secondary adaptation to continuing stress. Exercise physiol. gives us an obvious example: The untrained athlete responds to the increased oxygen demands of exercise by increasing cardiac output via increased HR. The trained athlete increases cardiac output by mild cardiac dilatation and increased ejection fracture-- allowing increased cardiac output with a lower HR.

As a side note, I am not sure whether you were joking, but the ability to volunteer for medical experiments has obviously virtually no impact on incarceration rates. 

I'm not as dumb as I look....I couldn't be.

 

[CharonY]

59 minutes ago, guidoLamoto said:

Mechanism may unclear on the details at the specific biomolecular/genetic level, but in general we can say it has to do with recruitment/inhibition of genes &/or certain enzymes.

Well, most biological actions on the cellular  level involve the actions of proteins on one level or or another so that is not very useful for the understanding of the actual mechanism.