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2,4-dinitrophenol is probably the most effective weight-loss
drug in existence. Basically, it short-
circuits your mitochondria, so that they generate heat (and
consume glucose) without doing any
useful ATP production. I may have mentioned this
otherwhere or elsewhen here on the HB
that I have an obsession with quick-fix weight loss.
Properly-used, DNP can double or triple your basal
metabolism. This means that you can sit in
front of the TV 24/7 and lose more weight than you would
by dieting and exercise.
Howevertheless, there are problems. Since you're
generating extra heat, there's a limit to how
much DNP you can take before you become dangerously
hyperthermic. Consequently, DNP is not
approved for general use, and therefore people buy it on
the webternet (or, if they're clever, from
a scientific supplier). This is not conducive to sensible
dosing, and hence such people occasionally
take themselves entirely out of the gene pool.
So, what do to?
Well, unspired by the linked idea for a voluntary prisoner-
style diet regime, here is MaxCo.'s latest
proposal. For a modestly exhorbitant fee, you get a room
at MaxCo.'s fat-farm. It has TV,
broadband, and access to some of the world's finest chefs
who will cater for your every culinary
whim. It also has an atmosphere somewhat enriched in
oxygen. However, it lacks a bed.
Instead of the bed, there is a padded tub through which
chilled water is circulated. This is where
you will live, eat and sleep for the duration of your stay.
You are also required, every 6 hours, to
swallow a small thermometric pill which will constantly
record and report your core temperature.
You are then dosed, at regular intervals, with several times
the normal lethal limit of DNP. The
temperature of water in your tub is constantly adjusted to
keep your core temperature within
normal limits. More or less by definition, you will feel
comfortably warm however cold the water.
In the oxygen-enriched atmosphere and the coolth of your
tub, your body can burn off calories at 4,5... maybe 8 times
normal rate. Even if you make full use of the in-house
dining experience, the fat will simply melt
away. A 48-hour stay should be roughly equivalent to a 7-
day fast, shifting perhaps 7-10lb. Early
check-out, before the DNP has been tailed off and allowed
to clear your system, is strongly
discouraged and may lead to, ah, complete check-out.
The linked idea
[MaxwellBuchanan, Jun 08 2015]
Controlled Release DNP
[bs0u0155, Jan 26 2016]
||Is cataract surgery included in the fee?
||//cataract surgery// Ah yes. Forgot about that one.
DNP does appear to cause cataracts but, strangely,
almost exclusively in women.
||//Does this act on particular cell types ?// I'm not
sure how uniformly
DNP gets into difference cell types, but I'd guess it
gets into most quite
easily since it's small and fairly organicky. Once it's
in, it should affect
the mitochondria uniformly.
||Think of each mitochondrion as a little generator
fuelled by glucose.
DNA just reduces the efficiency of the generator, by
circuiting it. So, instead of maybe 15% of the glucose
energy going into
heat, maybe 50% goes into heat. The more active
the cell, the harder
the generator is working and, particularly with DNP,
the more waste
heat it generates.
||Fat cells themselves don't do much, so making their
efficient won't have much effect (i.e., if your
generator only has to
drive a single LED, making the generator inefficient
will only waste a
little bit of energy as heat). But muscle, brain or
liver cells work hard,
so making _their_ mitochondria inefficient leads to a
lot of wasted
energy. And that energy will come ultimately from
fat stored (and
released) by the fat cells.
||// is there a similar chemical the body produces in
quantities that vary
between hi-metabolism and low-metabolism types//
I think (hazy
recall) that brown fat cells contain a protein which
similar to their own mitochondria. This enables
brown fat to run its
mitochondria very wastefully, thereby generating
heat. There's some
research on inducing normal fat cells to become
brown fat cells, to help
weight loss. But I don't think (again, not sure) that
this explains the
difference between "naturally skinny"* people and
"naturally fat" people.
Equally, I don't think it explains differences in core
temperature - some
people just have their thermostats set a little
||[Note to self: must resist the "temptation" to
[Vernon]esquely put quote-marks around perfectly
"ordinary" words and phrases.]
||You lucky, lucky person, you.
||//Pretty sure it does for a large percentage from
what I've read.// Possibly. But all the studies I've
seen (OK, let's be frank here - all the TV science
documentaries I've watched) have concluded that
"natural skinniness" is down to things like eating
habits, activity patterns and fidgeting. That said,
there may be some variation in basal metabolisms.
||//put quote-marks around perfectly "ordinary" words and phrases//
||sp. ' "perfectly ordinary" '
||I reckon there would be an upper limit on the efficiency of your system using internal heating and skin cooling as you've described. At some point, the heat transfer rate would need to be high enough that you'd be causing frostbite in their extremities.
||So you need a more efficient cooling mechanism. It turns out the body has a relatively efficient internal heat management system, which also doubles as the nutrient transfer (amongst other things) system - ie the bloodstream.
||What you need to do is artificially cool the bloodstream. I propose hooking the victim (patient, whatever) up to a modified dialysis type machine with an inbuilt heat exchanger. Some experimentation may be required to determine what the lethal lower boundary is for blood temperature entering the body.
||Eventually, after some experimentation, you might end up with a system whereby blood is extracted and re-introduced from multiple locations to maximise heat transfer and minimise local area damage.
||I was expecting the idea to include USING the waste heat to some extent, such as generating electricity. (Yes, like in The Matrix.)
||Ha! so, had this idea. Didn't write it down, so have a bun
with a side of mild jealousy. Right, so, where were we...
||//2,4-dinitrophenol is probably the most effective
weight-loss drug in existence//
||it's good, combine with sodium liothyronine for extra
||//Basically, it short- circuits your mitochondria, so that
they generate heat (and consume glucose) without doing
any useful ATP production.//
||Glucose, nah, mitochondria don't even know what that
is... lactate, pyruvate, acetate, glutamate, and crucially
here, the beta oxidation of fatty acids.
||//It also has an atmosphere somewhat enriched in
oxygen// Possibly a bad idea, the only true antioxidants
are catalase and the electron transport chain, increasing
the partial pressure of one while inhibiting the other...
||// Even if you make full use of the in-house dining
experience, the fat will simply melt away//
||Bodybuilders using dnp describe any carbs as being turned
directly to heat.... this might be ill advised.
////cataract surgery// Ah yes. Forgot about that one.
DNP does appear to cause cataracts but, strangely,
almost exclusively in women.//
||They messed up the dosing, men and women weigh
different amounts, they knew this even back then, but
the split of tissues is off. Men have MANY more
mitochondria, due to more muscle, brain and liver tissue.
||//Fat cells themselves don't do much, so making their
mitochondria less efficient won't have much effect (i.e.,
if your generator only has to drive a single LED, making
the generator inefficient will only waste a little bit of
energy as heat)//
||This might be at the extreme end, but it doesn't matter.
Mitochondria prioritize their membrane potential above
all. They will happily CONSUME ATP to ensure they stay
polarized. One depolarized mitochondria can consume
HUGE amounts of substrate, this is, in fact the positive
control at the end of respiration experiments.
||//that brown fat cells contain a protein which does
something similar to their own mitochondria. This
enables brown fat to run its mitochondria very
wastefully, thereby generating heat. There's some
research on inducing normal fat cells to become brown
fat cells, to help weight loss.//
||Antarctic researchers upregulate UCPs in their brown fat,
white fat becomes brown fat. No need for dnp, just lower
people into ice baths, their shivering and so on can easily
consume 10,000 per day, right up until they beg for
||//sodium liothyronine// Interesting.
||//Mitochondria prioritize their membrane potential
above all. They will happily CONSUME ATP to ensure
they stay polarized.// Ah - even better then!
||//No need for dnp, just lower people into ice baths//
We ran that one past Sales and Marketing, and got a
negative response. It seems that people just won't
pay to be kept painfully cold.
||Get a celebrity or two on board, triple whatever asking
price that you had in mind and you're off to the races.
||[Maxwell Buchanan]'s "AMAZING" weight loss regime -
DOCTORS HATE HIM! (nothing to do with the weight loss
thing - they just do.)
||// Better living through chemistry //
||// Mejor vida con química //
|| [Marcado-para-eslogan] DELETED
||Having a damned good think about this, the liver is a bit of
an issue. When the mitochondrial chemiosmotic gradient is
partially uncoupled you create heat. The liver is close to
cooking itself anyway... it's right on the edge, heat wise.
Second, with all the tissues in the body screaming for
glucose, as glycolysis fuel to supplement their failing
mitochondrial ATP generation, the liver is stressed. It needs
a good supply of ATP. Various lipid metabolism... needs liver
mitochondria... we need a little specificity and targeting.
||//we need a little specificity and targeting//
||Targeting schmargeting. If people can take dose X
while going about their daily lives, they can take
dose nX while being chilled, where n>>1.
||//one of those drugs where you inject a rat with a
100x overdose and it explodes//
||I wish. MaxCo. has been trying to develop a rat-
exploding drug for a long time, and results have been
||At one point, our head of research reported some
very promising results. However, we eventually
discovered that he'd been injecting the rats with
nitroglycerine and then making them jump off a high
table. We gave him an excellent reference when he
applied for a position at BorgCo.
||Still, on the plus side, his work (however flawed) did
lead to the development of our anti-personell
squirrel and active-denial vole.
||looks like DNP is back in the game <link>
||Also, if you believe one research group, low levels of
DNP throughout a mouse's life increase its lifespan,
supposedly because it mimics some of the effects of
caloric restriction. And gods know that what we
really need are thin, long-lived mice.