Effect of a diet rich in sunflower oil on aspects of lipid metabolism in the genetically-obese rat

Aspects of the lipid metabolism of male, obese and lean Zucker rats were compared using animals which had been fed ad libitum for 32 days on a diet (HS) which contained 200 g sunflowerseed oil/kg or one (LS) which contained 50 g/kg of the oil. When compared with the LS diet, the HS diet decreased the characteristic lipid accretion in the liver of obese rats from 126 mg (LS) to 81 mg (HS)/g wet weight; corresponding values for the lean rats were 39 mg and 56 mg/g wet weight of liver, respectively. The HS diet depressed lipid synthesis de novo by liver homogenates and decreased the Δ9-desaturase activity of liver microsomes from obese and clean rats by about 50%. Δ9-Desaturase activity in vitro was also depressed by the addition of linoleic acid to liver microsomes from both obese and lean rats fed ad libitum on a standard laboratory diet. Depressed Δ9-desaturase activity, due to ingestion of the HS diet, was reflected in lower ratios of 16∶1/16∶0 and 18∶1/18∶0 fatty acids in tissue lipids from obese and lean rats. Ingestion of the HS compared with the LS diet resulted in increased proportions of 18∶2ω6 in liver lipids and adipose tissue triacylglycerols of obese and lean rats. The HS diet also increased the proportions of 20∶4ω6 in adipose triacylglycerols of obese and lean rats and in liver lipids of obese animals but not in their lean littermates.     

Δ6 and Δ5 desaturase activities in liver from obese zucker rats at different ages

Δ6 Desaturation of linoleic acid (18∶2 n−6) and Δ5 desaturation of dihomo-γ-linolenic acid (20∶3 n−6) were measured in liver microsomes from genetically obese Zucker rats (fa/fa) and from their lean littermates (Fa/−). Both groups were fed a balanced commercial diet. The rats were 6, 9 and 12 weeks old, which corresponded to stages in their active growth period. The content of total fatty acids and n−6 polyunsaturated fatty acids in whole liver and liver microsomes was also determined in order to ascertain how the desaturase activities measuredin vitro reflected regulation of essential fatty acid metabolismin vivo. Contrary to values obtained for Δ6 desaturation, Δ5 desaturation at nonsaturating substrate levels were lower in obese rats than in lean controls. In contrast, at saturating substrate level, the maximal Δ5 desaturase activities were the same in both phenotypes and they increased with age. Study of Δ5 desaturation kinetics (1/V vs 1/S) showed that V_m did not differ between 12-week-old obese and lean rats, whereas K_M in obese rats was much lower than in controls, expressing the very low affinity of the enzyme for the substrate in obese animals. The fatty acid composition of liver lipids reflected the results of desaturase activitiesin vitro. In particular, the ratios 20∶4 n−6/20∶3 n−6 were lower in obese rats than in lean rats, which can be explained by the lower conversion of 20∶3 n−6 into 20∶4 n−6 by Δ5 desaturation. However, the total amount of 20∶4 n−6 in the whole liver did not differ between phenotypes, whatever their age. This work presents evidence for a relationship between the changes in fatty acid compositional data in hepatic total lipids, total lipids of liver microsomes and modifications of fatty acid desaturase activities in the genetically obese Zucker rat.     

Effects of age and dietary essential fatty acids on desaturase activities and on fatty acid composition of liver microsomal phospholipids of adult rats

The combined effects of age and dietary n−6 and n−3 fatty acids were studied in 3-, 6- and 9-month-old rats. At each age, two groups were fed diets containing 5% (w/w) of vegetable oils rich in either 18∶3n−6 (borage group) or 18∶3n−6 plus 18∶4n−3 (black currant group), for a period increasing with age. A control group was fed the essential fatty acids 18∶2n−6 and 18∶3n−3 only. For each group, Δ6, Δ5 and δ9 desaturase activities were measured in liver microsomes, and fatty acid composition was determined in microsomal phospholipids. Desaturase activity varied as a function of age and dietary lipids. Δ6 Desaturation of 18∶3n−3 was more sensitive to these factors while Δ6 desaturation of 18∶2n−6 and Δ9 desaturation were more dependent on season than the other two. Desaturase activity was influenced more by the black currant than by the borage diet, especially at 6 and 9 months of age. A large proportion of arachidonic acid was maintained in the microsomes independent of the diet. Changes in the fatty acid composition did not strictly reflect the differences in desaturase activities. The effects of the two factors (age and diet) on the activities of the desaturases are complex, suggesting that the enzymes are susceptible to other factors as well.     

Effect of simvastatin on desaturase activities in liver from lean and obese zucker rats

The effect of simvastatin, a hypocholesterolemic drug, on the biosynthesis of arachidonic acid was studied in obese and lean Zucker rats. After administration of 2 mg/kg body weight/d for 13 d, Δ6 and Δ5 desaturase activities were measured in liver microsomes at two substrate concentrations. In untreated rats, the Δ6 desaturation rate was similar in the obese and lean rats when measured at saturating substrate levels, whereas Δ5 desaturation was lower in the obese animals. Treatment with simvastatin did not change Δ6 desaturation in either phenotype but increased Δ5 desaturation in obese rats to reach the unchanged rate observed in lean animals. The changes were not reflected in the fatty acid composition of liver microsomal phospholipids when expressed as μg fatty acid/g of liver.     

Effects of conjugated linoleic acid and troglitazone on lipid accumulation and composition in lean and Zucker diabetic fatty (fa/fa) rats

Dietary CLA has been shown to enhance glucose tolerance in several animal models, but in mice it induces insulin resistance and lipodystrophy. In this study, the effects of 2 wk of diet supplementation with either 1,5% CLA or 0.2% troglitazone (TZD), an insulin-sensitizing thiazolidinedione, on glucose tolerance, lipid accumulation, and composition of both lean and Zucker diabetic fatty (fa/fa; ZDF) rats were examined. Compared with lean rats, which maintained normal glucose tolerances after 2 wk of feeding regardless of diet, ZDF rats fed a control diet (CON) had significantly worsened glucose tolerance. ZDF rats fed CLA and TZD diets, however, maintained normal glucose tolerances. In contrast to the significantly elevated lipid levels in ZDF rats fed the CON diet, concentrations of plasma FFA and TG in ZDF rats fed CLA and TZD diets were normalized. A similar reduction of plasma lipid levels was observed in lean rats fed CLA and TZD compared with lean rats fed the CON diet. Although ZDF CON rats developed significant hepatic steatosis, both CLA-and TZD-fed rats had hepatic TG levels similar to those of lean rats. Both lean and ZDF rats fed the CLA diet had reduced adipose mass compared with respective genotype controls; however, TZD had no effect. Ratios of 16∶1/16∶0 and 18∶1/18∶0 FA, surrogate markers for stearoyl-CoA desaturase-1 (SCD-1) activity, were reduced in livers of ZDF rats fed CLA and TZD diets. These results show that, like TZD, CLA normalizes glucose tolerance and plasma lipids and also improves hepatic steatosis and FA composition in ZDF rats. The effects of CLA and TZD on hepatic lipid composition suggest that the effects of these two agents on glucose tolerance may be associated with a reduction in SCD-1.     

Hepatic Δ9, Δ6, and Δ5 desaturations in non-insulin-dependent diabetes mellitus eSS rats

Both diabetes mellitus type 1 and diabetes mellitus type 2 are widespread diseases that alter carbohydrate and lipid metabolism. e Stilmann-Salgado (eSS) rats are experimental animals that spontaneously evolve to a state similar to that of young people affected by non-insulin-dependent diabetes mellitus (NIDDM; type 2). Using 6-mon-old eSS rats that, according to the literature [Martinez, S.M., Tarrés, M.C., Montenegro, S, Milo, R., Picena, J.C., Figueroa, N., and Rabasa, S.R. (1988) Spontaneous Diabetes in eSS Rats, Acta Diabetol. Lat. 25, 303–313], had already developed insulin resistance, we investigated the changes evoked on Δ9, Δ6, and Δ5 liver desaturases. The abundance of mRNA and enzymatic activities were measured, as well as the FA composition of liver microsomal lipids. Compared to control rats, the mRNA content and activity of SCD-1 (stearoyl CoA-desaturase, isoform of the Δ9 desaturase) were significantly higher, urase, isoform of the Δ9 desaturase) were significantly higher, whereas the mRNA and activities of Δ6 and Δ5 desaturases were not significantly modified. Correspondingly, the proportion of 18∶1n−9 and the ratios of 18∶1n−9/18∶0 and 16∶1/16∶0 in lipids were significantly increased, whereas the proportion of 20∶4n−6 was unaltered. These effects were found while glycemia was constant or increased. The results are completely opposite those described in insulin-dependent diabetes mellitus (type 1), in which a depression of all the desaturases is found. They suggest that in eSS rats, the activities of the desaturases were not modified by an insulin-resistance effect. Moreover, we suggest that the enhancement of SCD-1 activity might be considered as another typical sign of the NIDDM syndrome, because it has also been found in other animal models of NIDDM, for example, the ones evoked by the sucrose-rich diet and in the Zucker rat.     

Relationship between mouse liver Δ9 desaturase activity and plasma lipids

This study was undertaken to investigate the total plasma fatty acid composition and the relationship between plasma triacylglycerol (TG) levels and liver Δ9 desaturase activity in mice fed n−3 and/or n−6 fatty acid or hydrogenated coconut oil (HCO) (maximum 25 mg/g) supplemented diets. Generally, plasma TG levels and Δ9 desaturase activity were inversely correlated with the ratio of the sum of long chain n−3 fatty acids to 18∶2n−6 and to the ratio of the sum of long chain n−3 fatty acids to 18∶n−3, but they were positively correlated with the ratio of products and substrates (18∶1/18∶0) of the enzyme in plasma total lipids. The n−3 fatty acid (mainly 20∶5n−3) enriched diet, when compared to the HCO diet at 21 d, caused a significant reduction in plasma TG levels but not in Δ9 desaturase activity. However, a marked reduction in plasma TG content (50–60%) and Δ9 desaturase activity (55–70%) was observed when both 20∶5n−3 and 18∶3n−6 were supplemented in the diet. The plasma TG levels and Δ9 desaturase activity rose again when the animals were fed the HCO diet or chow. The results suggest that low dose supplementation of a mixture of n−3 (mainly 20∶5n−3) and n−6 (18∶3n−6) fatty acids modified both plasma TG content and liver Δ9 desaturase activity, in parallel.     

Effect of low levels of dietary fish oil on fatty acid desaturation and tissue fatty acids in obese and lean rats

The effect of very low levels of dietary long-chain n−3 fatty acids on Δ6 desaturation of linoleic acid (18∶2n−6) and α-linolenic acid (18∶3n−3), and on Δ5 desaturation of dihomo-γ-linolenic acid (20∶3n−6), in liver microsomes and its influence on tissue fatty acids were examined in obese and lean Zucker rats and in Wistar rats. Animals fed for 12 wk a balanced diet containing ca. 200 mg of long-chain polyunsaturated n−3 fatty acids per 100 g of diet were compared to those fed the same amount of α-linoleic acid. Low amounts of long-chain n−3 fatty acids greatly inhibited Δ6 desaturation of 18∶2n−6 and Δ5 desaturation of 20∶3n−6, while Δ6 desaturation of 18∶3n−3 was not inhibited in Zucker rats and was even stimulated in Wistar rats. Inhibition of the biosynthesis of long-chain n−6 fatty acids was reflected in a decrease in arachidonic acid (20∶4n−6) content of serum lipids when fasting, and also in the phospholipid fatty acids of liver microsomes. On the contrary, heart and kidney phospholipids did not develop any decrease in 20∶4n−6 during fish oil ingestion. Docosahexaenoic acid (22∶6n−3), present in the dietary fish oil, was increased in serum lipids and in liver microsome, heart, and kidney phospholipids.     

Effects of dietary fats on fatty acid composition and Δ5 desaturase in normal and diabetic rats

We have studied the effect of various diets on the phospholipid fatty acid composition andin vitro Δ5 desaturase activity of hepatic microsomes derived either from the normal or streptozotocin-induced diabetic rat. The diets studied were the standard rat chow diet and a basal fat-free diet supplemented either with 20 percent saturated fat, 20 percent unsaturated fat, or 20 percent menhaden oil. Phospholipid fatty acid composition analysis revealed that the normal rat fed the saturated fat or menhaden oil diet had significantly decreased arachidonate levels, consistent with decreased Δ5 desaturase activities and decreased 18∶2n−6 intake. On the contrary, the unsaturated fat diet decreased dihomo-γ-linolenate and increased arachidonate levels, without increased Δ5 desaturase activity. Streptozotocininduced diabetes resulted in decreased arachidonate and Δ5 desaturase activity. The unsaturated fat diet fed to the diabetic rat also failed to correct this decreased Δ5 desaturase activity. The unsaturated fatty acids in this diet also displaced a substantial amount of n−3 fatty acids in both normal and diabetic microsomes, due to the competition between these two fatty acid families for incorporation into the membrane phospholipids. Conversely, the menhaden oil diet fed to the normal and diabetic rats displaced n−6 fatty acids, reduced Δ5 desaturase activity, and enhanced 22∶6n−3 incorporation into diabetic microsomes.     

Severe fatty liver in rats fed a fat-free ethanol diet,and its prevention by small amounts of dietary arachidonate

Rats were fed ethanol and a fat-free diet for 30 days to determine whether dietary fat is needed for the development of fatty liver. The severity of fatty liver was similar to that of rats fed an isocaloric diet with 35% fat. Small amounts (29 mg/day) of dietary arachidonic acid prevented alcoholic fatty liver. Rats fed either the alcohol (AF) or control (CF) fat-free diets developed essential fatty acid deficiency (EFAD) as measured by the triene/tetraene ratio of liver and plasma lipids. Rats fed arachidonic acid (AA, alcohol and CA, control diets) did not develop EFAD. Although EFAD alone did not cause the development of fatty liver, the combination of dietary ethanol and EFAD did. The ratios of 16∶1/16∶0 and 18∶1/18∶0 in liver lipids indicated that desaturase enzymes were less active and lipogenesis was reduced in rats fed the AA diet compared to those fed the AF diet. In contrast, stimulated lipogenesis appears to have been the cause of fatty liver in rats fed the AF diet. Presented at the XII International Congress of Nutrition, San Diego, CA, August 1981. Abbreviations: Diets are indicated as fat-free with ethanol (AF), fat-free without ethanol (CF), or similar diets with 0.9% of the calories as arachidonic acid with (AA) or without (CA) ethanol. The composition of these diets is discribed in the text and Table 1.     

Desaturase activities in rat model of insulin resistance induced by a sucrose-rich diet

A sucrose-rich diet, as compared with a similar starch diet, induces a time-dependent typical noninsulin-dependent diabetes syndrome characterized by insulin resistance in rats. Within the first 3 wk, there was glucose intolerance associated with hyperinsulinemia, hypertriglyceridemia, and high plasma FFA. In this study, we examined the effect of the sucrose-rich diet vs. the starch diet during short-(3 wk) and long-term treatment (6 mon) on hepatic Δ9, Δ6, and Δ5 desaturases. These enzymes modulate monounsaturated FA and PUFA biosynthesis, respectively. Sucrose feeding (3 wk) caused an initial hyperinsulinemia that was normalized within 6 mon. In the early period (3 wk), stearoyl-CoA desaturase-1 (SCD-1) mRNA and activity were decreased, whereas Δ6 desaturase mRNA abundance and Δ6 and Δ5 desaturase activities remained unchanged. After 6 mon of sucrose feeding, activities of the Δ9, Δ6, and Δ5 desaturases were each increased. The SCD-1 and Δ6 desaturase mRNA were also correspondingly higher. These increases were consistent with an increase in oleic acid, the 20∶4/18∶2 ratio, and 22∶4n−6 and 22∶5n−6 acids in liver and muscle lipids. On the other hand, the percentage of 22∶6n−3 acid was decreased. In conclusion, a sucrose-rich diet after 6 mon induces an increase in rat liver SCD-1 and Δ6 desaturase mRNA and enzymatic activities that are opposite to the changes reported in insulin-dependent diabetes mellitus. It appears that neither blood insulin levels nor insulin resistance is a factor affecting the Δ9, Δ6, and Δ5 desaturase changes in mRNA and activity found with the sucrose-rich diet.     

Effects of zinc deficiency and castration on fatty acid composition and desaturation in rats

The effects of zinc deficiency and testosterone on fatty acid composition of plasma lipids and microsomes of liver, intestine and testes were studied. The activities of fatty acid desaturase (Δ6 and Δ5) in rat liver and testes were also measured. A significant decrease in the level of arachidonic acid was observed in plasma of normal rats fed the zinc-deficient diet. Castration significantly decreased arachidonic acid but increased 20∶3 fatty acid, which is negligible in normal rats. Testosterone and zinc administration restored arachidonic acid to normal values. Zinc deficiency does not significantly change the fatty acid profile in liver, but castration decreased both arachidonic and 22∶6 fatty acid. Intestinal mucosal microsomes showed that the predominant fatty acid in this tissue, palmitic acid, is independent of zinc status, whereas polyunsaturated fatty acids 18∶2 and 20∶4 were decreased by zinc-deficient diet or castration. Zinc deficiency sharply decreased 22∶5 fatty acid and to some extent, other polyunsaturated fatty acids in testis microsomes. These changes in fatty acids are in agreement with increased Δ9 desaturation and decreased Δ5 desaturase activity. In testes, both Δ6 and Δ5 desaturase activities are decreased in zinc deficiency. It appears that zinc influences the conversion of linoleic to arachidonic acid, whereas testosterone influences Δ6 desaturase activity. The data suggest that zinc deficiency may be one of the important factors in the causation of polyunsaturated fatty acid deficiency, which in turn, may induce serum hypertriglyceridemia.     

Daily variations of the biosynthesis and composition of fatty acids in rats fed on complete and fat-free diets

This report describes the daily changes in fatty acid composition and fatty acid desaturation in rats feeding on a complete diet and a fat-free diet successively. Rats on a complete diet showed a good homeostasis in the percentage of fatty acid in plasma, with a possible palmitic acid rhythm, but the fat-free diet initiated an essential fatty acid-deficient pattern in a few hours. The light-dark period in animals feeding on a complete diet motivates a feeding rhythm that causes changes in linoleic and arachidonic acids in the whole liver and microsomes that are related to Δ6 and Δ5 desaturase activities. The patterns of Δ6 and Δ5 desaturase changes were different. Linoleic acid intake during the dark periods (complete diet feeding) caused a decrease of Δ6 desaturase activity and the activation of Δ5 desaturation that led to an increase of arachidonic acid biosynthesis. The feeding of a fat-free diet eliminated the rhythm observed in linoleic and arachidonic acid composition in the liver and changed the desaturase rhythms. The Δ9 desaturase activity in the liver also showed a daily rhythm in the complete-diet period that disappeared with the change to a fat-free diet, while the activity increased markedly. A negative correlation existed between the percentage of linoleic acid in the liver and the Δ9 desaturase activity. However, no correlation was found between Δ9 desaturase activity and the percentage of 16∶1 and 18∶1 in the complete-diet period.     

Effect of early postnatal dietary sterculate on the fatty acid composition of rat liver and brain lipids

Pregnant rats were fed a high carbohydrate diet containing either 1% trilinolein or 1% trilinolein with 0.2% methyl sterculate from 18 day gestation to 21 day postpartum. The pups were weaned at 21 days and continued on the same diet for an additional 10 days. The microsomal stearyl CoA desaturase activities of the liver were effectively inhibited. Liver triglycerides showed increases in the saturated fatty acids concentrations at the expense of the corresponding monoenes. The concentration ofcis 6–7 octadecenoic acid was elevated. In liver phospholipids, the concentration of stearic acid was increased without a corresponding decrease in the oleic acid content. A drastic decrease in the nervonic acid (24∶1, n−9) concentration of liver sphingomyelin was observed. The lipids of the brain did not contain sterculic acid, and brain desaturase activity was unaffected. There was no significant change in the concentration of monoenoic acids from 16∶1 to 22∶1. However, nervonic acid was decreased by 32%. These results suggest that brain nervonic acid may be derived from a precursor other than oleic acid.     

Liver Δ5 and Δ6 desaturase activity differs among laboratory rat strains

This study was designed to examine the variations among rat strains in hepatic fatty acid desaturase activities and to determine the correlations between the activities of these enzymes and the levels of each microsomal fatty acid. Wistar rats from two different sources as well as Long-Evans and Sprague-Dawley rats were selected to assess, under standard and identical experimental conditions, the liver Δ5 and Δ6 desaturase activities. Both desaturase activities were significantly reduced by 56% in Sprague-Dawley rats when compared to BB-Wistar control rats, whereas intermediate reduced values were detected in Wistar (CR) and Long-Evans strains. The activities of Δ5 and Δ6 desaturases were significantly and positively correlated with each other. However, no significant correlations were detected between either Δ5 or Δ6 desaturase activities and levels of any of their fatty acid substrates or any other of the major microsomal fatty acids. Fatty acid composition of microsomal total lipids showed strain dependency. A positive correlation was detected between the microsomal levels of the two major final products of both desaturases, namely 20∶4n−6 and 22∶6n−3. In general, the sum of n−3 or n−6 fatty acids but not the ratio of one to the other, varied among rat strains. The study demonstrated that Δ6 and Δ5 desaturase activities are strain-related. The data also suggested that (i) the desaturation activity should be measured and not predicted from the fatty acid composition and (ii) different rat strains should be used for lipid metabolic studies before conclusions are drawn for rats in general.     

Dietary arachidonic acid and hepatic desaturation of fatty acids in obese zucker rats

The effect of low levels of dietary arachidonic acid (20:4n-6) on Δ6 desaturation of linoleic acid (18:2n-6) and α-linolenic acid (18:3n-3), and on Δ5 desaturation of dihomo-γ-linolenic acid (20:3n-6) were studied in liver microsomes of obese Zucker rats, in comparison with their lean littermates. Fatty acid composition of serum total lipids and of phospholipids from liver microsomes and from total heart and kidney was determined to see whether modifications of desaturation rate, if any, were reflected in the tissue fatty acid profiles. Animals fed for 12 wk on a balanced diet, containing 20:4n-6 and 18:2n-6, were compared to those fed 18:2n-6 only. The low amount of dietary 20:4n-6 greatly inhibited Δ6 desaturation of 18:2n-6 and Δ5 desaturation of 20:3n-6, whereas Δ6 desaturation of 18:3n-3 was slightly increased in obese rats. Inhibition of the biosynthesis of long-chain n-6 fatty acids by dietary arachidonic acid was only slightly reflected in the 20:4n-6 content of liver microsome phospholipids. On the contrary, the enrichment of serum total lipids and heart and kidney phospholipids in this fatty acid was pronounced, more in obese than in lean animals. Our results show that, although the desaturation rate of the n-6 fatty acids in liver microsomes was greatly decreased by the presence of arachidonic acid in the diet, the tissue phospholipid content in arachidonic acid was not depressed. The potentiality of synthesis of eicosanoids of the 2 family from this fatty acid is consequently not lower, especially in obese rats, in which certain tissues are deficient in arachidonic acid, in comparison with their lean littermates.     

Interrelationship between dietarytrans fatty acids and the 6- and 9-desaturases in the rat

Studies are reported on the effects of dietarytrans fatty acids on the 6- and 9-acyl desaturase activities in the liver microsomes of rats fed essential fatty acid (EFA)-deficient and non-FFA-deficient diets. In experiment I, weanling male rats were fed a semisynthetic diet with either 10% safflower oil (SAF) or 10% hydrogenated coconut oil (HCO). At the age of one year, half of the dietary fat was replaced by a supplement containing elaidate, linolelaidate andcis,trans-trans,cis-18∶2 (TRANS) for 12 weeks. In experiment II, male rats which were kept from weaning on a 10% SAF diet for one year received one of the following fat supplements for a 12-week period: 10% HCO, 9% HCO+1% TRANS, or 5% HCO+5% TRANS. Feeding TRANS depressed the 6-desaturase activity in the liver microsomes, especially in the EFA-deficient rats (HCO+TRANS group of experiment I). Unlike the 6-deaturase activity, the 9-desaturase activity was not inhibited by the dietarytrans fatty acids and was significantly stimulated in the non-EFA-deficient rats (SAF+TRANS group of experiment I and HCO+TRANS groups of experiment II). This was evidenced by incubation reactions and by comparisons of fatty acid consumptions and microsomal fatty acid levels, showing extra biosynthesis of 16∶1 and 18∶1 when TRANS was fed. The biosynthesis of essential (n−6) fatty acids was depressed by the TRANS supplement in EFA-deficient as well as in non-EFA-deficient animals.     

Effect of Ecdysterone on the Hepatic Transcriptome and Lipid Metabolism in Lean and Obese Zucker Rats

Conflicting reports exist with regard to the effect of ecdysterone, the predominating representative of steroid hormones in insects and plants, on hepatic and plasma lipid concentrations in different rodent models of obesity, fatty liver, and diabetes, indicating that the effect is dependent on the rodent model used. Here, the hypothesis was tested for the first time that ecdysterone causes lipid-lowering effects in genetically obese Zucker rats. To test this hypothesis, two groups of male obese Zucker rats (n = 8) were fed a nutrient-adequate diet supplemented without or with 0.5 g ecdysterone per kg diet. To study further if ecdysterone is capable of alleviating the strong lipid-synthetic activity in the liver of obese Zucker rats, the study included also two groups of male lean Zucker rats (n = 8) which also received either the ecdysterone-supplemented or the non-supplemented diet. While hepatic and plasma concentrations of triglycerides and cholesterol were markedly higher in the obese compared to the lean rats (p < 0.05), hepatic and plasma triglyceride and cholesterol concentrations did not differ between rats of the same genotype fed the diets without or with ecdysterone. In conclusion, the present study clearly shows that ecdysterone supplementation does not exhibit lipid-lowering actions in the liver and plasma of lean and obese Zucker rats.     

Effect of dietary fats on desaturase activities and the biosynthesis of fatty acids in rat-liver microsomes

Four groups of rats were fed diets containing 15% (w/w) high-oleic safflower oil (SFO, rich incis-18∶1 acids), a mixture of 80% partially hydrogenated soybean oil plus 20% corn oil (H+CO, rich intrans-18∶1 acids), lard (L, rich in saturated fatty acids) and corn oil (Co, rich in 18∶2ω6). Fatty acid composition of liver microsomes and activities of the Δ⁵, Δ⁶ and Δ⁹ desaturases were determined. Microsomal Δ⁶ desaturase activity and arachidonic acid were lower in the H+CO group compared with SFO of L. No difference was found in the Δ⁵ or Δ⁶ desaturase activity of CO and SFO groups. Thus, the oleic-acid level of the SFO diet had no effect on the metabolism of 18∶2ω6. Fluorescent polarization studies, usingtrans-parinaric acid as a probe, showed no differences between the physical states of phospholipid vesicles made from lipids isolated from each group. We concluded that thetrans-18∶1 acids in partially hydrogenated soybean oil have a more inhibitory effect than saturated acids on EFA metabolism, even in the presence of adequate amounts of essential fatty acid.     

Effect of different acids with Δ9,12-dienoic structures on Δ9 desaturation activity in rat liver microsomes

The effect of oral administration, for 24 or 48 hr, of different octadeca fatty acids containing a 9,12-dienoic structure on the fatty acid composition and Δ9 desaturation activity of liver microsomes of rat fed a fat-free diet was studied. The ethyl esters of linoelaidic and γ-linolenic acids, the methyl ester of linoleic acid and free columbinic acid were administered to rats maintained on a fat-free diet. The supplementation of the fat-free diet with linoelaidate produced no relevant changes in the fatty acid composition pattern of liver microsomes and did not modify the percentage of conversion of palmitic to palmitoleic acid. The addition of linoleate or γ-linolenate to the fat-free diet returned liver microsome Δ9 desaturation activity toward the control and partially restored the liver microsome fatty acid spectrum found in the fat-free diet. Columbinic acid (5-trans-9-cis,12-cis-18∶3), which cannot be transformed into arachidonic acid, also decreased the Δ9 desaturation activity enhanced by the fat-free diet and evoked changes in the microsomal fatty acid composition similar to those produced by the ω6 fatty acids. These results suggest that the modulation of Δ9 desaturase activity evoked by dietary administration of unsaturated acids of ω6 series would depend on thecis double bond configuration of these acids.