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Lipoprotein Metabolism
Our bodies have a very complex lipoprotein system. The lipoproteins within our
blood are transporters of fat and cholesterol. The lipoproteins contained within
the body are: chylomicrons, very-low-density lipoprotein (VLDL), intermediatedensity lipoprotein (IDL), low-density lipoprotein (LDL), and high-density
lipoprotein (HDL). All of these as well as the liver and adipose tissue play a role
in lipoprotein metabolism.
Chylomicrons are derived from dietary source intake (High fat intake); they are
not normally present in the bloodstream during the fasting state. Therefore, after
eating a large meal, fat is broken down by bile, which then travels to the
duodenum of the small intestine. The lining of the small intestine is made up of
enterocytes, epithelial cells; this is where chylomicrons are formed.
The
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the lipolytic pathway. It was shown that the lipoprotein lipase pathway does not
clear chylomicrons and VLDL particles equallychylomicrons are the preferred
substrate. Hence, non-fasting levels of triglycerides are an equal or better
predictor of cardiovascular disease compared with fasting levels because of the
fasting triglycerides and apoB100 secretion rates having little impact on
postprandial accumulation of the triglycerides, apoB48 or apoB100. The results
also showed that accumulation of triglycerides and apoB48 in the chylomicron
fraction is determined by the capacity of the lipolytic pathway, not the fasting
concentrations to determine postprandial lipid concentration of triglycerides and
apob48 in the chylomicron fraction. The conclusion of the findings identified that
the non-fasting triglyceride levels are major predictors of cardiovascular events.[2]
The newly formed nascent chylomicron exits the enterocyte via exocytosis and
passes through the lymphatic vessels and then it is slowly entered into the blood
stream to prevent drastic changes in the lipid content of your peripheral blood.
Once the nascent chylomicron has entered the circulator system and passed into
the bloodstream, they are going to obtain two new peripheral apolipoprotiens
donated from the HDL; apoE and apoC.
The apoE and apoC are transferred to the chylomicron from the HDL. At this
point, you have a fully mature chylomicron and from here it can take a number of
different paths.
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One path that the mature chylomicron can take a delivery process of the
triacylglycerides (TAG) to non-hepatic tissues, like the adipose and muscle.
During this process, TAG is removed from chylomicrons via intravascular
conversion to chylomicron remnants. For this process to occur, apoC is required.
ApoC is required in order to bind to enzyme lipoprotein lipase (LPL).
LPL
catalyzes the hydrolysis of the TAG within the chylomicron to occur on the
endothelial cell surface of the small blood vessels on adipose and muscle tissue,
which is used for energy and storage.
The binding of the enzyme to apoC and lipoprotein lipase allows for cleavage of
the TAG within the chylomicron to occur, transferring the free fatty acids and
glycerol to quickly be absorbed into the adipose/muscle cell.
In the past few years new perceptions into the metabolic properties of apoCs
have been provided. A number of important in vitro and in vivo studies were used
to find a role for each of the individual apoCs in lipoprotein metabolism. The
individuals apoCs are: apoC1, apoC2, and apoC3.
[1]
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[1]
Too much apoC2 on the lipoprotein particle has been demonstrated to inhibit
LPL-mediated hydrolysis of triglycerides.
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[1]
[7]
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Once the binding of the enzyme to apoC2 and lipoprotein lipase occurs, the TAG
are being broken down from the chylomicron to the tissue, the high TAG level in
the chylomicron continues to decrease, as the chylomicron becomes a smaller
particle, eventually causing the chylomicron to lose apoC2.
After the mature chylomicron has lost apoC2, it has now become a chylomicron
remnant. The chylomicron remnant still carries apoE. ApoE on the chylomicron
interacts with the chylomicron remnant receptors on the liver.
This binding interaction between the two causes the liver to then take up the
chylomicron remnant via endocytosis where the remaining triglycerides are put to
use and hydrolyzed by lysosomes. The hydrolysis releases the remaining fatty
acids and glycerol for storage or energy use.
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Cholesterol and cholesterol esters from the chylomicron remnant may be used
either to; covert bile salts and secrete it in the bile, secrete it into the bile as
neutral sterol, or are incorporated into VLDL or HDL and released into the blood.
The interaction of the LDL-apoB100, E receptors are the key to the cells
internalization of the LDL. Nascent VLDL is made in the Golgi apparatus of the
liver and additional apolipoproteins C and E are transferred from HDL. The fatty
acids from TAG are hydrolyzed by the lipoprotein lipase (LPL), which are found in
the adipose, aorta, heart, spleen, etc. As the TAG is removed from the VLDL the
particle becomes smaller and becomes an IDL, when the TAG are reduced by
IDL. Further loss of the TAG and it becomes a LDL via catabolism. The LDL
travels to the liver and it is taken up by ApoB-100 receptors found in the liver and
non-hepatic tissue. ApoB100 is essentially the sole protein on the surface of LDL,
and the lifetime of LDL in plasma appears to be determined mainly by the
availability of LDL receptors. Overall, 70% to 80% of LDL catabolism from
plasma occurs via the LDL receptor pathway, whereas the remaining tissue
uptake occurs by non-receptor or alternative-receptor pathways. [6]
There is a low affinity binding to the LDL to the liver because it only contains
apoB100 and lacks apoE and apoC. The liver receptor binds to apoE with a
higher affinity. This makes the half-life longer for LDL in the blood. Though, LDL
is the source of cholesterol for the body and the body needs cholesterol for cell
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membranes and for hormonal functioning, LDL can also be considered as the
bad cholesterol because free radicals in the blood bind to endothelium of blood
vessels and can oxidize excess LDL. The process is marked by the uptake of
LDL by phagocytic cells that become engorged with lipid, called foam cells. The
uptake will be accelerated if the apoB component of the LDL is modified by
oxidation.
accumulate fatty plaque from LDL and it can deposit the cholesterol beneath it,
which leads to atherosclerosis. [8]
Also, humans can also absorb oxidized fat, and oxidized dietary oils may also
promote atherogenesis in humans. [9]
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This
reduces the risk of the plaque build up formation and health risks. Since the
HDLs main job is to transport cholesterol esters to be excreted from the body, it
is correlated with a reduced cardiovascular health risk, hence its name the
good cholesterol.
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The general rule of thumb when it comes to fatty acid consumption is to consume
polyunsaturated fat because it has shown to be hypocholesterolemic, not to
consume saturated or trans fatty acids because it is hypercholesterolemic and
the monounsaturated fatty acids are neutral and have no effect on cholesterol
serum. These are just basic guideline but it is all very complicated.
No fatty acid is the same and they all have different properties. Saturated fatty
acids contain no double bonds and are solid in room temperature. The reason
that they are solid at room temperature is because SFA can stack themselves
due to the composition of the carbon and hydrogen. The melting point of this
formation would be higher due packed arrangement allowing SFA to be solid at
room temperature.
(14:0), and Palmitic Acid (16:0). SFAs are found mostly from animals, dairy
products, including butter, but it is also found in some plants like palm oil,
coconut oil and hydrogenated vegetable oils.
There are two classes of unsaturated fatty acids, monounsaturated (MUFA) and
polyunsaturated (PUFA). PUFAs contain more than one double bone in their
structure and MUFAs contain one double bond. The double bond can form
alterations in the conformation of the body to cis or trans. The trans geometry
allows for stacking which can allow the FAs to be solid at room temperature,
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where are the cis conformation doesnt allow for stacking permitting the FA to be
liquid at room temperature. The main source of unsaturated FAs is from plants.
All classes of FAs have different cholesterolemic effects on the body. Studies
show that polyunsaturated fatty acids elicit the most potent hypocholesterolemic
effects. Where as, myristic acid is the most potent of the saturated fat, when
compared to lauric and palmitic.
In the study of Peter L. Zock 36 women and 23 men were fed three diets. All the
diets differed from each other in palmitic (palm oil), oleic (high-oleic acid
sunflower oil), and myristic acid (high myristic acid fat) content by about 10% of
total energy. Each of these diets was fed to the men and woman for 3 weeks in
a random order. The diet mainly consisted of solid foods with prepared menus;
the differences in the diet were achieved by the use of special margarines where
about 10% of daily energy from oleic acid was replaced by palmitic acid or
myristic acid, and other dietary constituents, particularly lauric acid and trans fatty
acids, were virtually unchanged.
acid and palmitic acid both increased the total cholesterol level, HDL and the
LDL, more so with myristic than the palmitic. [11]
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This evidence showed that myristic and palmitic saturated fatty acids should be
lower in dietary consumption.
On the other hand, a study done by Tine Tholstrup revealed that there is no
effect with total cholesterol with either acid. Two diets were fed to 12 men (ages
21-26) consisting of 40% of either myristic or palmitic acid for 3 weeks, with one
month in-between.
between the total cholesterol but the comparison of both diets resulted in an 8%
higher HDL (good) cholesterol and 8% lower ratio of LDL: HDL. [12]
(Tholstrup) compared the effect of myristic and palmitic acids alone, without the
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replacing the PUFA from the diet, but keeping it consistent in each diet. This
study only contained young, healthy men.
studies is that there is no consistency in the participants but there are two
different studies implicating different results. The gender may play an effect on
cholesterol levels. Also, because Zock replaced a 10 percent of PUFA with SFA
in each diet to be tested, it is unclear if the result of the increased levels of total
cholesterol and LDL is due to the decreased consumption of PUFA, the
increased consumption of SFA, or that of them together. A study with collective
implications may conclude different results, in the sense that there would be a
larger variety of participates and that PUFA were not being replaced perhaps the
results of the potency of myristic acid would be more clear.
Lauric Acid (12:0), also a saturated fatty acid has been studied by Denke. A
study was performed to determine the effects lauric acid on plasma lipids and
lipoproteins. This was done using 14 men that were fed 3 different liquid formula
based diets for 3 weeks at a time in random order with more than one week of
the participants resuming normal activity. The diet contained 40% of energy as
fat, 40% as carbohydrates, 20% as soy based protein, and a multivitamin
providing 100% of the recommended dietary allowance for vitamins. The only
difference in the three different diets was the consumption of fat type. One diet
consisted of high-oleic sunflower oil, one with high-palmitic palm oil, and one with
fat made by base catalyzed rearrangement of high-oleic sunflower oil and
trilaurin to compensate for the high lauric diet. The data implied that lauric acid
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Even
[13]
Lauric and palmitic acid are both saturated fatty acids and both revealed an
increase in total cholesterol and LDL cholesterol levels. Oleic acid is a PUFA
and did not show any increase in total cholesterol and LDL cholesterol. This
specific study shows that SFAs, lauric and especially palmitic acid, have negative
effects on lipoproteins and are hypercholesterolemic, therefore increasing TC
and LDL levels. On the contrary, Sundrams study revealed that palmitic acid
demonstrated that its effects were less hypercholesterolemic than that of the
lauric acid and myristic acid when both are combined. This was a double blind
cross over study with 17 normal cholesterolemic males. They were fed whole
foods that were designed to have 5% of energy exchange between palmitic and
the lauric + myristic acid, all of the other fatty acids were held constant. The diet
was during two 4-week period with 3 weeks in between where participants were
to resume back to normal customs.
incorporate FAs to fit a customary Malaysian diet. Everything used in this study
for the FA synthesis were blends made up of nature edible fats in order to
preserve the pattern of triglyceride molecular species normally encountered in
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foods. As in the other studies some fats were scientifically modified, this may
have made the results biased because of the manipulation of the saturated fatty
acids.
[14]
It appears that this study composed of young, healthy male participants that were
also delivered low dietary cholesterol.
effect on total blood cholesterol or LDL cholesterol. Healthy individuals can more
easily excrete cholesterol from the body because of the uptake from available
hepatic LDL receptors. These studies may be more beneficial if it were designed
around participants with hypercholesterolemia with compromised LDL receptors
in addition to the healthy participants so that results can be compared for further
analysis. The effect of SFA on the body seems to have a negative effect, but it
still seems unclear as to what degree.
A study done by Yu revealed that stearic acid (18:0), a long-chain saturated fatty
acid, has no effect on LDL-C, HDL-C, or total cholesterol. The study suggests
that because stearic acid is a different, unique SFA that it be distinguished from
other long chain SFA and not grouped with the when estimating the plasma
cholesterol response to change in dietary SFA. The study also stated that had a
neutral effect on total cholesterol, LDL-C, and HCL-C in men but it may lower
HDL-C in women, this appears to be significant based off of sufficient data. [15]
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As
mentioned in the study for stearic acid, the effect of stearic acid on HDL-C is
affected by sex, lowering HDL-C levels in females.
applicable to other interactions of fatty acid classes. Most studies of the studies
that were performed were gender specific to men. Though most organizations
support saturated fats to be a risk to our body, a recent review published in July
of 2014 by Schwab, claimed that convincing evidence that partial replacement of
SFA with PUFA decreases the risk of CVD, especially in men. There are a lot of
questions that arise within the public and health professions when it comes to
saturated fatty acids which is why there is controversy and weather the there are
health benefits or health risks involved with the consumption of SFA.
It is
When comparing the SFA results to MUFA, oleic acid (18:1) for examples above,
the results of total cholesterol and LDL cholesterol decreased with the
consumption of MUFA. Studies were also done to show the effect of MUFA with
that of carbohydrates and PUFAs.
[16]
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each. The total plasma cholesterol decreased by 7.7% and the LDL cholesterol
decreased by 14.4% when students were being fed the MUFA diet. There was
no significant change in HDL concentrations within this diet In comparison to the
carbohydrate diet, no significant change in any cholesterol concentrations
occurred which concluded that MUFAs have an independent effect on the body
with that of other dietary substances.
A second study done by the same group that tests MUFA to carbohydrate rich
diets studied the effects of MUFAs verses PUFAs. The study was done on 26
normal male students in a crossover study of MUFAs verses PUFAs fed
alternately during two 12-week periods. MUFA was supplemented into the diet in
the form of olive oil, avocado, and almonds and the PUFAs were added into the
diets with equal amounts of safflower oil, soy oil, and walnuts.
The results
revealed that dietary PUFA results in somewhat lower total cholesterol and LDL
concentrations whereas with MUFA the susceptibility of LDL to oxidative stress
still showed as lower as in the study with MUFAs vs. carbohydrates. The MUFA
diet revealed a decrease in total plasma cholesterol by 10% where as the PUFA
diet had a decrease of 16%, both had a decrease in overall total plasma
cholesterol concentrations but PUFA having more. The LDL concentrations also
exposed a lower concentration in both the MUFA and PUFA fed diet.
No
differences were found on the concentrations of HDL on both diets. The higher
glycemic carbohydrates dis show more of a risk that that of low glycemic
carbohydrates. All participants were given meals at school and a dietitian made
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[17]
focus on young male students and the results may not be applicable to other
populations including females. Responses may be different when comparing both
sexes in a similar trial. Also the study mentioned that most of the time meals
were completed, many portions of the meal that was not completed could have
included portions of the FA that was being measured, and this may tamper with
the final results of the study. Further investigation would be necessary to have
concise results.
Unsaturated fatty acids contain at least one double bond within the backbone.
This double bond allows for conformational changes to occur within the structure,
cis or trans.
difference on serum lipoproteins. Trans fatty acids have been shown to increase
lipoprotein (a) (Lp[a]), which is associated with high risk and premature coronary
artery disease and stroke. A study
[18]
increase in Lp(a) levels. In experiment 2, there was an increase in the oleic diet
to 32 md/l and an increase to 45 mg/l in the trans MUFA diet, both being
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significant. In experiment 3, Lp(a) levels were 69 mg/l on both the stearic diet
and the linoleic diet but rose to 85 mg/l on the trans diet. The conclusion showed
that trans MUFAs may increase serum levels of Lp(a), which means that this
configuration of MUFA may lead to an increase in heart disease or stroke.
Trans fatty acids (TFA) are unsaturated fatty acids with at least one double bond
in the trans configuration and are formed during the partial hydrogenation of
vegetable oils, a process that converts vegetable oils into semisolid fats that are
generally used in manufacturing processes.
[19]
consumed for three weeks each, in random order. The results found that the
effect of trans fatty acids on the serum lipoprotein profile is at least as
unfavorable as that of the cholesterol raising saturated fatty acids, because they
not only raise LDL cholesterol but also lower HDL cholesterol levels.
[20]
The
study suggests that replacing all trans fatty acids in the diet with oleic acid might
increase the level of HDL cholesterol by an average of 0.05 mmol/L, and
decrease the level of LDL cholesterol by 0.10 mmol/L.
Another study by Judd Et Al observed the effects of cis and trans MUFA and
SFA. The assessment was completed on 29 men and 29 women that consumed
controlled diets. The diets were one with high oleic (cis), moderate TFA, high
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TFA, and SFA blend. When comparing the oleic diet, LDL cholesterol levels
increased; moderate TFA = 6.0%, high TFA=7.8%, SFA= 9.0%. Though the
SFA increased levels of LDL cholesterol, it also increased HDL cholesterol by
3.5% high than oleic diet, where as the HDL cholesterol levels decreased with
the high TFA by 2.8%! Therefore, the results exposed that TFAs increases bad
[21]
This is favorable
The major
[19]
This is
cost efficient and resourceful to the industry because oils abundant in saturated
fats are expensive and scarcer in the USA.
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fats are in packaged foods, bakery products, margarines, and fried food but also
in meat and dairy products. And the average consumption of TFAs in the USA is
2-4% of the total daily energy intake consumed.
[20]
addressed would be, what types of diets is the majority of the USA ingesting? If
the majority of foods consumed are common foods with levels of TFA, the
population is at high risk.
According to Centers for Disease Control and Prevention the leading causes of
death in the Unites States in decreasing order are:
Heart disease
Cancer
Chronic lower respiratory diseases
Stroke
Accidents (unintentional injuries)
Alzheimer's disease
Diabetes
Influenza and Pneumonia
Nephritis, nephrotic syndrome, and nephrosis
There are many factors that contribute to cardiovascular heart disease like:
Gender, age, genetics, smoking, diabetes, obesity, and diet. TFAs have been
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proven increase LDL and decrease HDL which puts you at a very high risk for
heart disease. TFA consumption has also been linked to cancer (according to
Scientific Advisory Committee on Nutrition and Nutrition Research). The
[22,24,25]
[23]
. TFAs
TFAs not only effects the metabolic processes that correlate with the leading
causes of death but are also proven to cause inflammation which decreases your
immune function as well as increasing problems with reproduction by increasing
your risk for infertility
[27]
[29]
[28]
. TFAs have
many bodily functions. Soybean oil is a good source of omega 3 fatty acids, yet
partial hydrogenation, converting the oil to a trans isomer diminishes the benefits.
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TFAs have been exhibited to have detrimental effects on the body, more so than
SFAs. In fact, SFAs showed that with consumption increased the size of LDL,
which prevents atherosclerosis. It would be beneficial for the population to omit
all TFA from diet and to restrict SFAs. The omission of TFAs from consumption
may decrease the leading cause of leading death caused and will increase your
over all health. Also, if the population is sedentary, it would be beneficial to
incorporate endurance exercise into the daily regimen because it has been
shown to increase HDL cholesterol concentrations and therefore can contribute
to a lower risk of coronary heart disease [10].
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effects of TFAs yet has still ceased to finalize a proposal on the ban.
The FDA
should finalize the ban of TFAs and TFAs should no longer be considered GRAS.
The finalization of the proposal would be one phase closer in the right direction in
protecting Americans heath and safety. The official loss of GRAS labeling will
fundamentally improve the quality of Americans food, and citizens.
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