Function and metabolism
peroxisomal β-oxidation, it seems to be mainly |3-oxidized in peroxisomes (Madsen et al., 1998). Indeed, rats treated with dietary 22:6 (n-3)
tended to have a higher peroxisomal β-oxidation rate by increasing
several enzyme activities such as the fatty acyl-CoA oxidase or the 2,4dienoyl-CoA reductase NADPH-dependent (Willumsen et al., 1993). In
contrast, it had no effect on mitochondrial β-oxidation. This specific
effect of 22:6 (n-3) may explain the 60% apparent β-oxidation rate we
obtained in the present study with animals receiving the 22:6 (n-3) diet.
It was shown recently that 22:6 (n-3) was an effective activator of peroxisome
proliferator-activated receptors (PPARs). This nuclear receptor superfamily controls a variety of target genes involved in key steps of the longterm regulation of lipid metabolism (Lemberger et al., 1996).
Moreover, animals which had ingested DHA, deposited relatively
important amounts of 20:5 (n-3) and 22:5 (n-3) (14% of n-3 fatty acids
accumulated). The net retroconversion of 22:6 (n-3) to 20:5 (n-3) and
22:5 (n-3) was quantitatively more important than the net conversion
from α-linolenate (about 8% of (n-3) fatty acids accumulated). Retroconversion of 22:6 (n-3) to 20:5 (n-3) is a peroxisomal pathway involving
only one cycle of β-oxidation. Then the 22:5 (n-3) deposit mostly
originated from the chain elongation of 20:5 (n-3), which explains the
lower content of 22:5 (n-3) compared to 20:5 (n-3) (6.2% versus 7.6%
of (n-3) fatty acids accumulated). The rate of retroconversion that we
found was slightly higher than that measured in vivo in rats fed a standard diet after ingestion of a single dose of triacylglycerol containing
[
13 C] 22:6 (n-3) (Brossard et al., 1996). This difference was probably
due to the fact that the standard diet did not contain appreciable
amounts of 22:6 (n-3). In accordance with the above conclusion, retroconversion by peroxisomal β-oxidation of 22:6 (n-3) seemed to be
enhanced by the dietary 22:6 (n-3). The whole body deposition of 22:6
(n-3) in group “22:6 (n-3)”, was twice as high as in group “18:3 (n3)”. In brain, the amount was similar in both groups (3.7 ± 0.7 mg
versus 3.2 ± 0.7 mg) which suggests that the 200 mg 18:3 (n-3) or
22:6 (n-3) supply covered the requirements of the brain in the growing
rat. As compared to 18:3 (n-3), the deposition of 22:6 (n-3) m total fat
was less important. This might result in a less efficient lipoproteinlipase activity of hydrolysis towards long-chain fatty acid and/or a poor
specificity of triacylglycerol acyltransferase for 22:6 (n-3). Lastly, deposition of 22:6 (n-3) was more important in the remaining carcass, the
heaviest compartment. We supposed that 22:6 (n-3) was incorporated
mostly in phospholipids of muscles but further study is required to
confirm this hypothesis.
Conclusion
Our results showed that, in the growing rat receiving a minimal supply
of (n-3) fatty acids, dietary 22:6 (n-3) was as much β-oxidized as its
essential precursor althought following different metabolic pathways
161
peroxisomal β-oxidation, it seems to be mainly |3-oxidized in peroxisomes (Madsen et al., 1998). Indeed, rats treated with dietary 22:6 (n-3)
tended to have a higher peroxisomal β-oxidation rate by increasing
several enzyme activities such as the fatty acyl-CoA oxidase or the 2,4dienoyl-CoA reductase NADPH-dependent (Willumsen et al., 1993). In
contrast, it had no effect on mitochondrial β-oxidation. This specific
effect of 22:6 (n-3) may explain the 60% apparent β-oxidation rate we
obtained in the present study with animals receiving the 22:6 (n-3) diet.
It was shown recently that 22:6 (n-3) was an effective activator of peroxisome
proliferator-activated receptors (PPARs). This nuclear receptor superfamily controls a variety of target genes involved in key steps of the longterm regulation of lipid metabolism (Lemberger et al., 1996).
Moreover, animals which had ingested DHA, deposited relatively
important amounts of 20:5 (n-3) and 22:5 (n-3) (14% of n-3 fatty acids
accumulated). The net retroconversion of 22:6 (n-3) to 20:5 (n-3) and
22:5 (n-3) was quantitatively more important than the net conversion
from α-linolenate (about 8% of (n-3) fatty acids accumulated). Retroconversion of 22:6 (n-3) to 20:5 (n-3) is a peroxisomal pathway involving
only one cycle of β-oxidation. Then the 22:5 (n-3) deposit mostly
originated from the chain elongation of 20:5 (n-3), which explains the
lower content of 22:5 (n-3) compared to 20:5 (n-3) (6.2% versus 7.6%
of (n-3) fatty acids accumulated). The rate of retroconversion that we
found was slightly higher than that measured in vivo in rats fed a standard diet after ingestion of a single dose of triacylglycerol containing
[
13 C] 22:6 (n-3) (Brossard et al., 1996). This difference was probably
due to the fact that the standard diet did not contain appreciable
amounts of 22:6 (n-3). In accordance with the above conclusion, retroconversion by peroxisomal β-oxidation of 22:6 (n-3) seemed to be
enhanced by the dietary 22:6 (n-3). The whole body deposition of 22:6
(n-3) in group “22:6 (n-3)”, was twice as high as in group “18:3 (n3)”. In brain, the amount was similar in both groups (3.7 ± 0.7 mg
versus 3.2 ± 0.7 mg) which suggests that the 200 mg 18:3 (n-3) or
22:6 (n-3) supply covered the requirements of the brain in the growing
rat. As compared to 18:3 (n-3), the deposition of 22:6 (n-3) m total fat
was less important. This might result in a less efficient lipoproteinlipase activity of hydrolysis towards long-chain fatty acid and/or a poor
specificity of triacylglycerol acyltransferase for 22:6 (n-3). Lastly, deposition of 22:6 (n-3) was more important in the remaining carcass, the
heaviest compartment. We supposed that 22:6 (n-3) was incorporated
mostly in phospholipids of muscles but further study is required to
confirm this hypothesis.
Conclusion
Our results showed that, in the growing rat receiving a minimal supply
of (n-3) fatty acids, dietary 22:6 (n-3) was as much β-oxidized as its
essential precursor althought following different metabolic pathways
161