Metabolomics reveals that hepatic stearoyl-CoA desaturase
1 downregulation exacerbates inflammation and acute colitis.
Further, this could be due to low activities of [delta]-5- and [delta]-6-desaturases
, which are necessary for the formation of LC [omega]-3 PUFAs and/or the presence of certain dietary factors that interfere with the formation of EPA and DHA or their actions, such as high intake SFAs or TFAs, or the absence or deficiency of cofactors that are essential for the normal activity of desaturase
, such as vitamin C, selenium, folic acid, vitamin E, pyridoxine, and [beta]-carotene (153).
Inhibition of several genes, such as stearoyl-CoA desaturase
1 (SCD-1), acetyl-CoA carboxylases 1 (ACC1) and diacylglycerol acyltransferase 2 (DGAT2) resulted in decreased fat synthesis, increased fat oxidation (burning) and a clearing of fat in the liver.
But when modified with desaturase
from plants, including Arabidopis, and then fed a diet of vegetable oil fatty acids, the altered yeast's lipid storage capability increases up to sevenfold.
The recently issued patent (United States Patent 6,107,334) covers a method of delivering gammalinolenic acid (GLA), a fatty acid found in high concentrations in glycerolipids of certain plants, and a delta-5 desaturase
inhibitor to derive the beneficial effects of GLA -- reported to safely improve clinical symptoms of several inflammatory disorders -- without its harmful effects when given alone.
Shanklin's team has been focusing on desaturase
enzymes, which create a double bond between a pair of carbons in that molecular backbone.
The expression levels of 10 genes: retinoid X receptor alpha (RXRA), peroxisome proliferator-activated receptor gamma (PPARG), phospholipid transfer protein (PLTP), stearoylCoA desaturase
(SCD), nuclear receptor subfamily 1 group H member 3 (NR1H3), fatty acid binding protein 3 (FABP3), carnitine palmitoyltransferase II (CPT2), acyl-Coenzyme A dehydrogenase long chain (ACADL), acyl-Coenzyme A oxidase 2 branched chain (ACOX2), and fatty acid binding protein 4 (FABP4), showed significant differences in gene expression between the low- and high-marbled groups (p < 0.
The researchers mainly focused on polymorphisms in the fatty acid desaturase
(FADS) gene cluster that encodes the delta-5 and delta-6 desaturase
enzymes involved in the synthesis of long-chain fatty acids of the series omega-3 and omega-6.
The first downstream metabolite of linoleic acid is gamma-linolenic acid, formed via the activity of the delta-6 desaturase
These reductions could result neither from fat malabsorption, because concentrations of the two essential fatty acids, LA and ALA, were not altered, nor from a decrease in desaturase
activities, since n-6 long-chain PUFAs were not altered.
1999) found that coplanar PCBs have a significant effect on the reduced synthesis of physiologically essential long-chain unsaturated fatty acids, such as arachidonic acid in rat liver, by suppressing delta-5 and delta-6 desaturase
activities and thus allowing the omega-6 parent fatty acid, linoleic acid, to accumulate.
They noted, for instance, that the reduced activity of one enzyme - a delta-5 desaturase
-"was directly related to estimates of insulin resistance in this study.