MiFR: Eat More %Fat?
mik...@my-deja.com
I've come across this paper:
Comp Biochem Physiol B 1984;78(4):817-26
A comparison of mitochondrial respiration and membrane lipid composition
in the
rat and marmoset following dietary lipid supplementation.
McMurchie EJ, Gibson RA, Charnock JS, McIntosh GH
In comparison to animals fed low fat diets, mitochondrial
respiration in the marmoset was reduced by high fat diets irrespective of
the dietary level of lipid saturation.
PMID: 6432427, UI: 84284129
Though it's not mentioned in the abstract, the paper also asserts that
the state 3: state 4 ratio was not altered by the different diets. So
there was lower metabolic rate (depending on substrate, state 3 absolute
levels went down between ~ 1/9 nd ~ 1/3) with no increase in e- fumbling.
I also note from your book (p.17) that "ubisemiquinone exists only
fleetingly withie CoQ is interacting with Complexes I of III. However,
its existence is ... the weak link in the chain, because it can
spontaneously revert to ubiquinone" and thus fumble e-. I take this to
imply that this fumbling does NOT occur (or is at least much less likely
to occur) in the transfer of e- from FADH2 via fatty acyl CoA
dehydrogenase to CoQ. IIRC, you actually say this explicitly somewhere in
your corpus, tho' I can't find t just this minute.
If a higher-fat diet slows metabolism without making mt any sloppier, and
if some of the e- from fat are transferred into ETS via a less fumble-
prone route, then shouldn't a higher-fat diet (with constant caloric
intake) to some extent reduce mt oxidative stress and thus slow aging?
If so:how reasonable is it to say, "respiration rate declined ~ [so
much], and the increase in fat means an decrease in the e-flow from I to
CoQ of [so much], which is half [?] of the 1-2% of total e- fumbled, so
root damage to MIM (granted the inefficacy of MIMS AOs) should go down
[so much]"? And can one then extrapolate to how much aging should be
slowed down?
Or if (as I suspect) this is both too many variables to mess with and
also leaves OUT too many variables (eg. LDL oxidizablity, as per the full
monty of RHH), is it at least fair to say that a higher fat diet would
slow aging by at least 1%? Any better estimate? Or am I missing something
colossal?
-Michael
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Before you buy.
Aubrey de Grey
Michael Rae wrote:
> McMurchie et al, Comp Biochem Physiol B 1984;78(4):817-26
> In comparison to animals fed low fat diets, mitochondrial respiration
> in the marmoset was reduced by high fat diets irrespective of the
> dietary level of lipid saturation.
Hm - and this effect was not seen in the rats. Not sure what this
means.
> Though it's not mentioned in the abstract, the paper also asserts that
> the state 3: state 4 ratio was not altered by the different diets. So
> there was lower metabolic rate (depending on substrate, state 3
> absolute levels went down between ~ 1/9 nd ~ 1/3) with no increase in
> e- fumbling.
That doesn't absolutely follow. "Mitochondrial respiration" means the
rate of respiration of isolated mitochondria (extracted from cells) in
defined states (states 3 and 4), and it doesn't necessarily tell us
about the metabolic rate (per unit mass, i.e. the specific metabolic
rate) of the intact organism. In particular, if the state 3:state 4
ratio (normally termed the respiratory control ratio) was unaltered
then state 3 respiration and state 4 respiration were both lower in
isolated mitochondria, but if the fat-supplemented organism was running
closer to state 3 (i.e. keeping its ADP supply higher) then the
organism's specific metabolic rate (which wasn't measured) could have
been unaltered.
However, for the sake of argment let's presume that the marmosets'
specific metabolic rate was indeed lowered by the high-fat diet.
> I also note from your book (p.17) that "ubisemiquinone exists only
> fleetingly withie CoQ is interacting with Complexes I of III. However,
> its existence is ... the weak link in the chain, because it can
> spontaneously revert to ubiquinone" and thus fumble e-. I take this to
> imply that this fumbling does NOT occur (or is at least much less
> likely to occur) in the transfer of e- from FADH2 via fatty acyl CoA
> dehydrogenase to CoQ. IIRC, you actually say this explicitly somewhere
> in your corpus, tho' I can't find t just this minute.
You have it right; the explicit statement is in a footnote on p140.
> If a higher-fat diet slows metabolism without making mt any sloppier, and
> if some of the e- from fat are transferred into ETS via a less fumble-
> prone route, then shouldn't a higher-fat diet (with constant caloric
> intake) to some extent reduce mt oxidative stress and thus slow aging?
Possibly, but the effect would be slight: for each two-carbon slice
of a fatty acid, only two electrons enter the electron transport chain
via the fatty acyl CoA dehydrogenase, whereas eight enter via Complex
I and two via Complex II. In the case of carbohydrate metabolism, if
we presume that the glycerophosphate dehydrogenase pathway is not used
we get a bigger ratio through Complex I, five out of six rather than
four, but that's a pretty small difference.
> If so:how reasonable is it to say, "respiration rate declined ~ [so
> much], and the increase in fat means an decrease in the e-flow from I to
> CoQ of [so much], which is half [?] of the 1-2% of total e- fumbled, so
> root damage to MIM (granted the inefficacy of MIMS AOs) should go down
> [so much]"? And can one then extrapolate to how much aging should be
> slowed down?
Too many variables, I think. A simpler argument that just says that
"respiration rate declined [so much] so e- flow through Complexes I and
III declined by that same amount, so the rate of e- fumbling declined
by about that same amount" seems more persuasive.
> Or if (as I suspect) this is both too many variables to mess with and
> also leaves OUT too many variables (eg. LDL oxidizablity, as per the full
> monty of RHH), is it at least fair to say that a higher fat diet would
> slow aging by at least 1%? Any better estimate? Or am I missing something
> colossal?
I think that in view of the small differences in how much each enzyme
is used and the quite substantial differences in metabolic rate, it is
certainly justified to explore whether highly fat-biased diets might
lower metabolic rate in other primates, as well as other variations on
the study you mention. I found an interesting related study in Medline:
Yerboeket-van de Venne and Westerterp, Appetite 1996 Jun;26(3):287-300
found a reduction in energy expenditure from medium or high fat diet
relative to low, but only in people described as "restrained eaters".
This may suggest that the reduction in metabolic rate is associated
with retention of the fat, i.e. weight gain, which curiously was not
measured in the McMurchie study.
Aubrey de Grey
rjk3
ag...@mole.bio.cam.ac.uk (Aubrey de Grey) wrote:
>
> Michael Rae wrote:
>
> > McMurchie et al, Comp Biochem Physiol B 1984;78(4):817-26
>
> > In comparison to animals fed low fat diets, mitochondrial
respiration
> > in the marmoset was reduced by high fat diets irrespective of the
> > dietary level of lipid saturation.
>
> Hm - and this effect was not seen in the rats. Not sure what this
> means.
>
> >
Marmosets hibernate, rats do not. The metabolic adaptations
necessary to lower metabolic rate for hibernation may have some bearing
on this: perhaps a certain amount of body fat triggers some of the
hibernation systems, lowering metabolic rate?
mik...@my-deja.com
ag...@mole.bio.cam.ac.uk (Aubrey de Grey) wrote:
>
> Michael Rae wrote:
>
> > McMurchie et al, Comp Biochem Physiol B 1984;78(4):817-26
>
> > In comparison to animals fed low fat diets, mitochondrial respiration
> > in the marmoset was reduced by high fat diets irrespective of the
> > dietary level of lipid saturation.
>
> Hm - and this effect was not seen in the rats. Not sure what this
> means.
I found an interesting related study in Medline:
> Yerboeket-van de Venne and Westerterp, Appetite 1996 Jun;26(3):287-300
> [ PMID: 8800484]found a reduction in energy expenditure from medium or high fat diet
> relative to low, but only in people described as "restrained eaters".
> This may suggest that the reduction in metabolic rate is associated
> with retention of the fat, i.e. weight gain, which curiously was not
> measured in the McMurchie study.
>
Huh? Should we not conclude the OPPOSITE re: the fat accumulation: if the
reduction in energy expenditure only happened in “restrained eaters,”
then presumably it happens in people who are NOT getting fat, no? And the
abstract concludes that "The results suggest that a low-fat diet would be
beneficial in the treatment of obesity, especially if subjects have a
restrained type of eating behaviour." They wouldn't come to that
conclusion if there were any evidence of fat accumulation; rather, the
reverse.
In any case, we CR folks are certainly “restrained eaters”! Does this not
at least suggest that high-fat diets, eaten in a restricted fashion,
lowers SMR? Indeed, a rodent study, referenced b Weindruch and Walford in
_The Retardation..._, found that
"Kubo ... found that LSs were most strikingly prolonged by DR when
moderate intakes (38% of energy as fat) ... were used." p. 59
... as MiFR would predict, granted that:
"High fat diets are used more efficiently than are low fat ones... Quite
probably the severity of the [CR] tolerable by animals could be increased
by feeding high fat diets... whether this would further increase
lifespan is worthy of study [see above quote: evidently, it DOES]
...*what* (not just how much) is eaten affects metabolism." -255
-Michael
Aubrey de Grey
rkj3 wrote:
> Marmosets hibernate, rats do not. The metabolic adaptations necessary
> to lower metabolic rate for hibernation may have some bearing on this:
> perhaps a certain amount of body fat triggers some of the hibernation
> systems, lowering metabolic rate?
Excellent suggestion. I find it very plausible.
Michael Rae wrote:
> Huh? Should we not conclude the OPPOSITE re: the fat accumulation
Absolutely right - I totally zoned out there. Moreover I didn't know
about the results you quote from W&W. I agree with your interpretation.
Aubrey de Grey