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Objective: The effect of dietary borage oil (rich in the gamma-linolenic acid [GLA]) on insulin sensitivity and lipid metabolism was compared with that of fish oil (rich in n-3 polyunsaturated fatty acids [PUFAs]) in high fat (HF) diet-induced insulin resistance (IR) of rats., Methods: Male Wistar rats were fed ad libitum for 3 weeks a standard laboratory chow (Controls) or high fat diet consisting of 70-cal % fat. In addition, a group of rats was fed high fat (HF) diet where a part of saturated fat was replaced with fish oil as a source of n-3 PUFAs (HF+FO), or borage oil as a source of GLA (HF+GLA). In vivo insulin action was assessed by the euglycemic hyperinsulinemic clamp. Glucose, insulin, free fatty acids (FFA), triglycerides (Tg) and glycerol levels in blood and tissue depots were also measured., Results: Increased levels of Tg, FFA and glycerol in circulation after HF diet were accompanied by their raised accumulation in insulin sensitive tissues. FO feeding lowered the concentration of all lipids in serum and prevented their accumulation in both tissues. On the other hand GLA supplementation into the high fat diet did not suppress increased levels of Tg, FFA and glycerol in circulation and tissue depots as well. FO feeding significantly reduced HF diet-induced in vivo IR, while GLA supplementation did not improve the in vivo insulin sensitivity in HF diet induced insulin resistance., Conclusions: 1. Substitution of FO into the high fat diet led to an improvement of in vivo insulin action; 2. this insulin sensitizing effect of FO was accompanied by a decrease of circulating Tg, FFA and glycerol levels in the postprandial state and by a lower lipid content in liver and skeletal muscle. 3. on the opposite, GLA treatment failed to improve in vivo insulin action; and 4. was associated with an adverse effect on lipid levels both in circulation and tissue depots.

Objective: We have shown previously that the impaired insulin action in hereditary hypertriglyceridemic (hHTg) rat is accompanied by a specific fatty acid (FA) profile in the insulin target tissues, possibly due to a desaturation defect. Thus, the aim of this study was to measure the enzymatic activity and gene expression of delta-6 desaturase in liver of hHTg rats and the tissue FA composition in relation to insulin action., Methods: Glucose, triglycerides and insulin in plasma were measured using commercially available enzymatic sets. The hepatic delta-6 desaturase activity in hHTg rats was determined radiometrically in a microsomal fraction using the 1-14C-linoleic acid as substrate. delta-6 Desaturase gene expression was measured by the Northern blot technique using a specific cDNA probe. Tissue FA profile was determined by gas chromatography in the total lipid fraction extracted to chloroform. The glucose turnover rate was measured in conscious freely moving animals with the aid of euglycemic hyperinsulinic clamp method., Results: Tissue triglycerides showed a high accumulation in skeletal muscle of hHTg rats. In the liver of these animals, a defect in delta-6 desaturase enzymatic activity was found, while the gene expression for delta-6 desaturase was not changed. Such decreased delta-6 desaturase activity in the liver was linked to a decrease of delta-6 desaturase index as calculated from the liver FA composition. Also the concentration of arachidonic acid (a final metabolite in the biosynthesis of polyunsaturated fatty acids of the n-6 series) was significantly decreased in hHTg rat liver. These changes in FA metabolism were accompanied by a decreased glucose infusion rate (a measure of in vivo insulin action) required to maintain euglycemia at hyperinsulinemia in hHTg rats, and correlated with the hepatic delta-6 desaturase activity., Conclusions: 1. hHTg rats showed a reduced activity of the delta-6 desaturase in liver without any changes in gene expression for this enzyme; 2. such impairment is accompanied by a lower delta-6 desaturase index (18:2n-6/18:3n-6) found in the liver of these animals and by specific FA profiles in the tissues, particularly regarding the amount of long-chain PUFAs and 18:2n-6 metabolites; and (4) these alterations seem to be related to the impaired insulin action of hHTg rats.