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The concept of dialysis is not new. You remove blood,
run it
through a semipermeable membrane, on the other side
of
which is a solution with the ideal concentrations of all
the
major physiological salts. If your kidneys aren't working
well, you'll have a build up of urea and other assorted
waste which will move out of the blood, through the
membrane and into the dialysis fluid. Now, wouldn't it
be
great if you could do that with fat? Yes, it would, a few
problems remain though.
First, getting fat out of the adipocytes. So, there's a few
ways of doing that. Glucagon, adrenocorticotrophic
hormone and adrenergic stimulation are the main ways
in
which an adipocyte knows to start chewing up
triglycerides
and secrete the resultant fatty acids and glycerol.
Glucagon is out, because it will force the liver to raise
the
blood sugar which will in turn increase insulin, which
strongly inhibits lipolysis. Adrenocorticotrphpic hormone
is
out, because it raises cortisol, which will suppress
lipolysis
again. That leaves us with stimulating the adrenergic
receptors. OK, so we just give a massive shot of
adrenaline? It would work, but might not be super
comfortable. Fortunately, the adipocyte has its own beta
adrenergic receptor, B3, which has pharmacological
agonists such as myrabegron*. For max effect, you'll
want
to inhibit the A2 receptors too, yohimbine or
atipamezole
will get you there. Now you'd be feeling OK, no racing
heart at least.
Right, where to put the fat.When secreted, fatty
acids bind to serum albumin. Serum albumin is a
multifunctional protein with specialized fatty acid
binding
sites. That's because free fatty acids floating around on
their own are pretty dangerous. Soon however, you
start to see free fatty acids because the capacity of the
serum albumin proteins becomes overwhelmed, so lets
get them. Run the blood
through a cartridge filled with immobilized recombinant
proteins which have many many fatty acid binding
sites. These simply bind all the free fatty acids leaving
the blood fat-free. Alternatively, a specialized high-
surface area polymer design could work. Anyhow,
between
patients, you can simply wash out the fatty acids with
solvent or detergent.
So, the benefits... well, if you're a man** you can get
about 25umol of fatty acids per 10^7 cells per hour with
high level stimulation. What does that mean? Well at
0.3nl/cell and a density of ~0.9 g/ml you're looking at
the
thick end of 2.3g/kg(of fat)/hr. So 10kg of excess fat,
10
hrs, 230g of fat lost. Expensive, difficult, slightly
dangerous, not particularly effective... I'm on a roll.
*Incidentally, popular blood pressure medicating beta-
blockers inhibit lipolysis. Not sure if that's good, bad
indifferent or what, but its interesting anyway.
**women max out at about half this rate, due to alpha-
beta receptor ratio differences.
Stealth liposuction
Stealth_20lipo-frac...0Body_20Fat_20Fairy
[not_morrison_rm, Jan 04 2016]
Homer's soul donut
https://www.youtube...watch?v=JFx3sojyPBY
[Voice, Jan 28 2017]
Donut Hell
https://www.youtube...watch?v=ydqkBG22Tk8
[Voice, Jan 28 2017]
Formation of oligopeptides in high yield under simple programmable conditions
https://www.nature....articles/ncomms9385
[Voice, Feb 20 2021]
[link]
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Why not just tumble the patient in a butter churn until the fat agglutinates, then remove it as a lump ? |
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There's a joke about an overweight magician.
His doctor told him to watch what he ate.
He replied, "I can't! I'm a magician! My hands move faster
than the eye!" |
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Dialyzing against a column of immobilized recombinant proteins is not too sci fi but I cannot think of a situation where it is done. I think the immense amounts of fats in a body might ask too much but this might be a slick way to overcome inborn metabolic defects where some substance builds up and causes trouble. I like very much the idea that the same column might be used repeatedly. |
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Doesn't the pathways mentioned all depend on subtle. Trying to get an agent to the site of action blows out the subtle of the inner workings. |
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Won't the dynamic lipid complexity, in the blood, just rebalance if a large amount is taken through dialysis, just like if you lost a whole lot of blood? |
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The dialysis is replacing that muscle burn.Why try to artificially stimulate it? Maybe some pre-dialysis exercise if necessary. |
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Without changing anything else, a depletion in lipid transport lipoproteins from the blood would cause a rebalancing. Repeating the washes over a longer period time shouldn't damage anything and in fact allow the body to adjust to new dynamic levels of pathway participants. |
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The manufacture of lipoprotein transport vesicles would also factor into the situation. |
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//immense amounts of fats in a body might ask too
much// |
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There's no upper limit to the size of the column, and let's
call this a column - the idea has much more in common
with affinity purification than dialysis, the upper limit is
the dead volume in the system which must be supplied
from the patient. There's no reason against simply
swapping out the column, washing with acetone or
something and then swapping it back in, that's just
plumbing. The really clever thing to do would be to
enzymatically "burn" the free fatty acids off. I worked out
most of it, but it needs cofactors and it gets complex.
Acetone's cheap, and not very toxic. |
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//Won't the dynamic lipid complexity, in the blood, just
rebalance if a large amount is taken through dialysis, just
like if you lost a whole lot of blood?// |
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The blood starts out with a fairly standard lipid balance.
In the blood, lipids generally cruise around as a
triglyceride, 3 fatty acids and a glycerol. They're normally
bound up with cholesterol and a whole bunch of proteins
in stable little balls. Now, free fatty acids are a little
rarer, they're unstable and dangerous, so one of the jobs
of the serum albumin proteins that the liver goes to great
trouble to make, is the binding and stabilization of free
fatty acids. Now, the fat cells pretty much have to
release fat in the free fatty acid (+ glycerol) form. We're
PROVOKING the biggest possible release of free fatty
acids from fat cells, normally a little dangerous, AND
when the normal serum albumin gets full, there's
signalling to stop the release. We're grabbing all the free
fatty acids as they leave the fat cells, before they get
much of a chance to turn off fat release. |
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//Is it really necessary to mess about too much, can you
just adjust the levels of stuff in blood to simulate
exercise ? Or does that come with its own adrenal load// |
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We don't want to mess with glucose too much. If glucose
goes down, you get glucagon signalling, which will prvoke
the breakdown of muscle, because you can't (easily) make
glucose from fat, which is really sad, because we can
make fat from glucose. You could supplement the blood
with valine, leucine and isoleucine (and/or booze), those
stop the muscles breaking down so much. |
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//This idea tries to promote an exercise state and with
limited knowledge I'd say that involves a depletion of
oxygen carrying ability so lipids are burned in favour of
sugar// |
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The sad reality of exercise, is that as intensity increases,
fatty acid release and use slows down. What I'm doing
here is telling the fat cells that it's major
starvation/emergency mode while telling everything else
that its just a normal inter-meal time. Then I'm mopping
up the free fatty acids before they can do harm, and
throwing them away. If you were to burn the fatty acids,
they would represent a non fossil fuel source. |
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[bs0u0155] What's your thoughts on how quickly the fatty acids can be washed out with the action of them painting plaques that have started or are about to start? Where is the best point to draw blood for washing? |
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If we have a clean exit and entry on the blood supply, the wash could be 24/7 without the need for metabolic pushing. Just change the cleaning cartridge and check the penetrations |
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creating an external loop of the blood supply is the biggest drawback of both regular haemodialysis and this idea. Often a grafted artery-vein shunt is installed, but that takes weeks to settle in, and is pretty major. Or you can have jugular access with a catheter similar to a Hickman/Central line which are only supposed to be for a few weeks, but I had one (for a different reason) for months. I think overall, this would be an excellent supplement to exercise. Imagine the increased motivation if you lost fat at 3-4x the rate? |
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//What's your thoughts on how quickly the fatty acids can be washed out with the action of them painting plaques that have started or are about to start?// |
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I'm not sure what you're saying here, but I'll have a stab anyhow. So, (and I am far from an expert, but I have run it past a heart person) atherosclerosis starts with a small injury, infiltration of macrophages, leaky arterial wall, (V)LDL sneaks in, macrophages do their best to mop up the (V)LDL, fail (because their stupid reactive oxygen species gun reacts badly with the nitric oxide needed for arterial function and the fat) and they die, releasing a load of fatty oxidized junk. Process repeats. Now, during all that, any free fatty acids that happen to be around can easily wander through the arterial wall and will dissolve nicely in the fatty junk. Can running the bs0FatMelter (patent applied for) help here? Well, you could run it without the drugs to clear circulating free fatty acids. Subsequently, because you've switched the equilibrium over quite hard, you may get movement of fatty acids out of plaques, probably onto vacant free fatty acid binding sites on the circulating serum albumin. Now, if, or how fast that occurs, is anybody's guess. If it's super slow, you're may starve the body of free fatty acids, which is bad for functioning. What you COULD do, is modify your column so that it is only capable of binding non-essential fatty acids, and even better, oxidized/trans fats. You're not gonna miss them. |
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Out of purely academic interest, what level of blood
alcohol would help in dissolving fatty deposits? |
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Well, all it does is inhibit gluconeogenesis. Which stops
secretion from adipocytes in the first place. It also stops fat
secretion from the liver. So basically it helps it stay and
accumulate where it is. |
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So, fat specific analogues of thyroid hormones have become available... so now the idea requires some GC-1 |
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You have to find a way to avoid stripping out the critical fat
soluble nutrients and such that are concentrated in the
lipid fraction of the blood and are communicated thusly. I
see the potential to make a person very very sick, and also
some pretty harsh whiplash effects from this sort of
therapy. The body might compensate by liberating massive
quantities of lipids which could lead to cardiovascular
problems. |
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If metabolism is a giant Fourier transformation that gives rise to the majors - breathing, heart rate, and consciousness then this is a trick, a short, compared to stressed, desired or just do exercise.Exercise, whatever form, is all natural and within the range of this miracle transformation of a healthy dynamic metabolism. |
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Don't get me wrong I like the idea and had the editation of a filter that could be placed into the vein or artery that pulled out the lipids. This could be inserted by hypodermic and retrieved after a period dependant on the absorptive lining. I just hope it is the special case rather than the norm. |
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//find a way to avoid stripping out the critical fat soluble nutrients and such that are concentrated in the lipid fraction of the blood and are communicated thusly.// |
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Nah, The vitamins have their own specific binding proteins. We're not including those. |
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//The body might compensate by liberating massive quantities of lipids which could lead to cardiovascular problems// |
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Well, these are only coming from one place, the adipocytes, and we're already doing our best to max out the free fatty acid release. The only thing the body can do is try to use the same mechanisms of stimulation. As soon as the column begins to be saturated we either swap in a new column or stop the drugs. |
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//of a filter that could be placed into the vein or artery
that pulled out the lipids. This could be inserted by
hypodermic and retrieved after a period dependant on the
absorptive lining.// |
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Ooohhh, you're off in scale by a big margin. We're going to
try and liberate kilograms on the scale of hours. |
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Rushing things always causes wear and tear. |
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This is genius though. This is the closest thing to teleporting out a specific molecule. If a target molecule can be trapped then this is a pure negative perturbation of the metabolism. Nearly a clean subtraction. |
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//Rushing things always causes wear and tear// |
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Which is why I advocate the title "wear and tear
inducing rushed walking" instead of the obsolete
"running". |
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If a target molecule can be trapped// Multiple repeats
of the serum albumin fatty acid binding domains on
some sort of tiny tethered protein would work, also
polyethylenamines with butyrated groups work well as a
fatty acid binder. Also, it might be a good idea to
supplement with a mix of ketone bodies while all this is
going on. Probably good to have a back up heart fuel. |
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You actually sound as if you understand this stuff, [bs]. Personally, I'm confident enough to allow [8th] to be used as an experimental subject. If it seems to be working, sign me up. |
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[bs], I've spoken to [8th] about this, and he's agreed to take part in the initial trials. Well, to be precise he said "Yes" in response to my question, which was couched in medical jargon (I believe the actual words I used were "would you like a doughnut?"). |
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More generally (and in the unlikely event that this dialysis malarkey doesn't work), why is not not possible to develop an adipocide - an agent that selectively kills fat cells? I'm thinking, maybe, something moderately nasty that is highly fat-soluble (and doesn't cross the blood-brain barrier). My understanding (which is usually wrong) is that the adult body tends not to produce more fat cells - it's just that the existing ones get fuller. So killing off 30% of them would seem like a good start. |
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That would work well in all sorts of other areas too, like politics ... |
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// medical jargon (I believe the actual words I used were "would you like a doughnut?"). // |
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Weasel words. Yes, we would like a doughnut, but we're not signing that form until we've got the actual comestible in our posession. |
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Ah, but I believe you ticked the box which allowed us to accept verbal consent. It was the box marked "Free doughnut?" |
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