Burning fats without producing ATP

Paul S. Brookes. brookes at uab.edu
Fri Jan 21 19:48:19 EST 2000

Had to comment on this......

In general, and in most experiments that have been done with isolated 
mito's (and a few in vivo ones), uncoupling mitochondria decreases their 
superoxide generation because of removing the block on electron transport 
and allowing the complexes to become oxidised again.  However, there are a 
few studies in which they found that uncouplers can promote superoxide 

I agree with Aubrey in saying that uncoupling mito's would seem to be a 
good strategy for wasting energy and burning fuels, but exactly how they 
make the mito's choose to burn fat instead of sugar is beyond me - maybe 
that's where the hydroxycitrate comes in (WTF does it do?).  On a 
historical note, the uncouplers most people use in the lab today were 
discovered because they are intermediates in the manufacture of 
explosives.  Someone noticed that explosives workers were ingesting the 
stuff and literally wasting away - unfortunately the desired weight loss 
effect also resulted in loss of life, so maybe uncoupling isn't such a good 
weight loss strategy after all.    Wonder if any data is available on the 
ageing symptoms of these folks?   Has anyone fed FCCP to rats and seen 
increased longevity?

The other thing to consider is that pyruvate is an excellent free radical 
scavenger and part of its effects (if it ever gets taken up into the cells 
above baseline levels) may be due to this.  On an experimental note..... if 
what they're saying is true (shuttling e-'s back through complex I to make 
NADH), then they should have done a control with rotenone.   In addition, I 
fail to see how NADH can shuttle e-'s to the cytosol, and then the e's can 
re-enter at CoQ.   In the context of ketogenesis its OK, as you're storing 
up something for later, but just making NADH doesn't burn energy, and will 
eventualy be feedback inhibited.  T he other thing worth remembering is 
that this is in hepatocytes, which don't have a lot of fat just lying 
around to be burned, but do have a lot of sugar.  In the whole animal 
you've still got to get round the obstacle of moving the fat from the 
adipocytes to the place where it's being burned.  It would make sense if 
they went after an adipocyte way of doing this, rather than th liver.  I 
for one don't want my liver too uncoupled  - think of all the work it has 
to do, like burninfg alcohol..... talking of which....


Dr. Paul S. Brookes.            (brookes at uab.edu)
UAB Department of Pathology,   G004 Volker Hall
1670 University Blvd., Birmingham AL 35294 USA
Tel (001) 205 934 1915     Fax (001) 205 934 1775

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