H. Osmundsen et al., EFFECTS OF DIETARY-TREATMENT OF RATS WITH EICOSAPENTAENOIC ACID OR DOCOSAHEXAENOIC ACID ON HEPATIC LIPID-METABOLISM, Biochemical journal, 331, 1998, pp. 153-160
(1) Effects of dietary treatment of male albino rats with eicosapentae
noic acid (EPA) or docosahexaenoic acid on hepatic mitochondrial lipid
metabolism have been investigated. (2) Mitochondria isolated from rat
s given these treatments were shown to have increased ability to respi
re on acyl-CoA esters in the presence of malonate. This effect was exp
ressed with most of the long-chain acyl-CoA esters used as substrates.
When malonate in the incubations was replaced with malate, mitochondr
ia from treated animals were found to exhibit diminished rates of resp
iration on polyunsaturated acyl-CoA esters, in particular linolenoyl-,
eicosapentaenoyl- and docosahexaenoyl-CoA. This phenomenon could not
be attributed to changes in activity of carnitine palmitoyltransferase
I or in peroxisomal beta-oxidation. (3) Uncoupled respiration on glut
amate, malate or succinate was also affected by treatment with EPA. Wi
th liver mitochondria isolated from rats that had been treated with a
omega-3 fatty acid in the fasted state, the respiratory rates were low
er than those observed with mitochondria isolated from control rats. R
espiratory rates with mitochondria isolated from rats given the omega-
3 fatty acid in the fed state was not significantly different from con
trol rates. (4) In rats treated with EPA in the fed state, the amount
of EPA incorporated into mitochondrial lipids was markedly more increa
sed as compared to rats given omega-3 fatty acid in the fasted state.
Incorporation of dietary EPA into tissue lipids was investigated, also
following mildronate treatment of rats (an inhibitor of carnitine bio
synthesis). (5) A hypolipidaemic effect of dietary EPA was only observ
ed when the fatty acid was given to fed rats. Rats treated with EPA in
the fasted state, in contrast, exhibited hypoglycaemia, the hypolipid
aemic effects now being absent. (6) These results suggest that hypolip
idaemia is most pronounced when the metabolic state favours incorporat
ion of dietary EPA into body lipids rather than its beta-oxidation, as
mediated by the fed/fasted transition or by treatment with mildronate
.