MiFR: Might CLA accelerate aging?

mikalra at my-deja.com mikalra at my-deja.com
Fri Mar 31 15:59:34 EST 2000


All:

A fair number of people are taking conjugated linoleic acid (CLA) for
weight loss or anti-cancer purposes. CLA has been reported to increase
metabolic rate (1). This is fine if your only concern is to shed pounds;
howerver, for those who are taking it for health purposes,if what is
increased is the whole-body SPECIFIC metabolic rate, this would make it
pro-aging due to increased mitochondrial superoxide production. But a
new paper (2) indicates that CLA increases beta-oxidation in adipose,
but not muscular, tissue. And the stuff has been repeatedly reported to
cause weight loss. Questions:

(1) Does the fact that b-oxidation is increased PROVE a higher metabolic
rate in terms of OXPHOS in fat tissue (presuming the cell is aerobic),
or might the aldehydes be metabolized by some other mechanism, or be
exported from the cell? Or might it just indicate a shift to fatty acid
from carb as the principle fuel source? Do adipocytes normally burn carb
to any significant degree? (1) mentions a change in nighttime fuel mix,
but the abstract gives no details...

(2) IF (2) demonstrates a higher metabolic rate in adipose tissues, is
it reasonable to assume that the higher metabolic rate reported in (1)
is entirely due to this? And if so,

(3) Since MiFR says that the preferrential amplification of anaerobic
mitochondria at the heart of aging is only an issue in postreplicative
cells (since replicating cells will constantly dilute anaerobic
mitochondria out), how seriously should we take this theoretical concern
from an anti-aging POV?

(4) Also, (1) reported that CLA reduced nighttime respiratory quotient,
so that less CO2 was exhaled per O2 inhaled. Doe this indicate less TCA
activity? How does this fit into the picture?

(5) Also, there are several reports that CLA increases lipid
peroxidation, including this recent one in humans (3), but I can't find
papers where they compared the peroxidation increases from feeding two
different groups euqal amounts of CLA and LA. Anyone know anything on
this point?

As always (and I hope not tiresomely), I look mostly to Aubrey for an
opinion where MiFR is concerned.

-Michael


(1)Am J Physiol 1998 Sep;275(3 Pt 2):R667-72


                       Effects of conjugated linoleic acid on body fat
and
                       energy metabolism in the mouse.

                       West DB, Delany JP, Camet PM, Blohm F, Truett AA,
Scimeca J

                       Pennington Biomedical Research Center, Louisiana
State University,
                       Baton Rouge, Louisiana 70808, USA.

                       Conjugated linoleic acid (CLA) is a naturally
occurring group of dienoic
                       derivatives of linoleic acid found in the fat of
beef and other ruminants.
                       CLA is reported to have effects on both tumor
development and body
                       fat in animal models. To further characterize the
metabolic effects of
                       CLA, male AKR/J mice were fed a high-fat (45
kcal%) or low-fat (15
                       kcal%) diet with or without CLA (2.46 mg/kcal;
1.2 and 1.0% by weight
                       in high- and low-fat diets, respectively) for 6
wk. CLA significantly
                       reduced energy intake, growth rate, adipose depot
weight, and carcass
                       lipid and protein content independent of diet
composition. Overall, the
                       reduction of adipose depot weight ranged from 43
to 88%, with the
                       retroperitoneal depot most sensitive to CLA. CLA
significantly increased
                       metabolic rate and decreased the nighttime
respiratory quotient. These
                       findings demonstrate that CLA reduces body fat by
several mechanisms,
                       including a reduced energy intake, increased
metabolic rate, and a shift in
                       the nocturnal fuel mix.

                       PMID: 9728060, UI: 98399776



(2) Lipids 2000 Jan;35(1):91-8



                       Effects of conjugated linoleic acid isomers on
                       lipid-metabolizing enzymes in male rats.

                       Martin JC, Gregoire S, Siess MH, Genty M,
Chardigny JM,
                       Berdeaux O, Juaneda P, Sebedio JL

                       I.N.R.A, Unite de Nutrition Lipidique, Dijon,
France.
                       jean-charles.martin at ibaic.u-psud.fr

                       Male weanling Wistar rats (n = 15), weighing
200-220 g, were allocated
                       for 6 wk to diets containing 1% (by weight) of
conjugated linoleic acid
                       (CLA), either as the 9c,11 t-isomer, the
10t,12c-isomer, or as a mixture
                       containing 45% of each of these isomers. The five
rats of the control
                       group received 1% of oleic acid instead. Selected
enzyme activities were
                       determined in different tissues after cellular
subfractionation. None of the
                       CLA-diet induced a hepatic
peroxisome-proliferation response, as
                       evidenced by a lack of change in the activity of
some characteristic
                       enzymes [i.e., acyl-CoA oxidase, CYP4A1, but also
carnitine
                       palmitoyltransferase-I (CPT-I)] or enzyme
affected by
                       peroxisome-proliferators (glutathione
S-transferase). In addition to the
                       liver, the activity of the rate-limiting
beta-oxidation enzyme in
                       mitochondria, CPT-I, did not change either in
skeletal muscle or in heart.
                       Conversely, its activity increased more than 30%
in the control value in
                       epididymal adipose tissue of the animals fed the
CLA-diets containing the
                       10t,12c-isomer. Conversely, the activity of
phosphatidate
                       phosphohydrolase, a rate-limiting enzyme in
glycerolipid neosynthesis,
                       remained unchanged in adipose tissue. Kinetic
studies conducted on
                       hepatic CPT-I and peroxisomal acyl-CoA oxidase
with CoA derivatives
                       predicted a different channeling of CLA isomers
through the
                       mitochondrial or the peroxisomal oxidation
pathways. In conclusion, the
                       10t,12c-CLA isomer seems to be more efficiently
utilized by the cells
                       than its 9c,11t homolog, though the Wistar rat
species appeared to be
                       poorly responsive to CLA diets for the effects
measured.

                       PMID: 10695929, UI: 20158476



(3) FEBS Lett 2000 Feb 18;468(1):33-6

                       Conjugated linoleic acid induces lipid
peroxidation in
                       humans.

                       Basu S, Smedman A, Vessby B

                       Section of Geriatrics/Clinical Nutrition
Research, Faculty of Medicine,
                       Uppsala University, Box 609, SE-751 25, Uppsala,
Sweden.

                       [Medline record in process]

                       Conjugated linoleic acid (CLA) is shown to have
chemoprotective
                       properties in various experimental cancer models.
CLA is easily oxidised
                       and it has been suggested that an increased lipid
oxidation may contribute
                       to the antitumorigenic effects. This report
investigates the urinary levels of
                       8-iso-PGF(2alpha), a major isoprostane and
                       15-keto-dihydro-PGF(2alpha), a major metabolite
of PGF(2alpha), as
                       indicators of non-enzymatic and enzymatic lipid
peroxidation after dietary
                       supplementation of CLA in healthy human subjects
for 3 months. A
                       significant increase of both 8-iso-PGF(2alpha)
and
                       15-keto-dihydro-PGF(2alpha) in urine was observed
after 3 months of
                       daily CLA intake (4.2 g/day) as compared to the
control group
                       (P<0.0001). Conjugated linoleic acid had no
effect on the serum
                       alpha-tocopherol levels. However,
gamma-tocopherol levels in the serum
                       increased significantly (P=0. 015) in the
CLA-treated group. Thus, CLA
                       may induce both non-enzymatic and enzymatic lipid
peroxidation in vivo.
                       Further studies of the mechanism behind, and the
possible consequences
                       of, the increased lipid peroxidation after CLA
supplementation are
                       urgently needed.

                       PMID: 10683436, UI: 20148605


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