Effects of starch-rich or fat-rich diets on metabolism, adiposity, and glycemia in immune-biased, C57BL/6 and BALB/c mice.

Diet maintains health by regulating host metabolism and immunity. The results revealed the consequence of starch-, unsaturated fat-, and saturated fat-rich diets on differentially immune-biased mice C57BL/6 and BALB/c. Time-course of various diets on differentially immune-biased mice revealed that starch-rich and unsaturated fat-rich diets reduced insulin resistance (IR) and visceral adiposity in BALB/c mice while a saturated fat-rich diet enhanced both parameters. In C57BL/6 mice, a fat-rich diet enhanced IR with time while visceral adiposity remained unchanged. Eight weeks' consumption of saturated fat-rich diet induced highest visceral adiposity in C57BL/6 mice, while the same diet resulted in the maximum IR in BALB/c mice. The current report presented a detailed metabolomic analysis of diets and evaluated differential index of each treatment for each mouse strain using a vector analysis of the multivariate linear discriminant data. The outcome identified metabolites that affected lipid and glucose metabolism to establish the inter-strain physiological differences.

Replacing Saturated Fats with Unsaturated Fats from Walnuts or Vegetable Oils Lowers Atherogenic Lipoprotein Classes Without Increasing Lipoprotein(a).

BACKGROUND: Walnuts have established lipid-/lipoprotein-lowering properties; however, their effect on lipoprotein subclasses has not been investigated. Furthermore, the mechanisms by which walnuts improve lipid/lipoprotein concentrations are incompletely understood. OBJECTIVES: We aimed to examine, as exploratory outcomes of this trial, the effect of replacing SFAs with unsaturated fats from walnuts or vegetable oils on lipoprotein subclasses, cholesterol efflux, and proprotein convertase subtilisin/kexin type 9 (PCSK9). METHODS: A randomized, crossover, controlled-feeding study was conducted in individuals at risk of cardiovascular disease (CVD) (n = 34; 62% men; mean ± SD age 44 ± 10 y; BMI: 30.1 ± 4.9 kg/m2). After a 2-wk run-in diet (12% SFAs, 7% PUFAs, 12% MUFAs), subjects consumed the following diets, in randomized order, for 6 wk: 1) walnut diet (WD) [57-99 g/d walnuts, 7% SFAs, 16% PUFAs [2.7% α-linolenic acid (ALA)], 9% MUFAs]; 2) walnut fatty acid-matched diet [7% SFAs, 16% PUFAs (2.6% ALA), 9% MUFAs]; and 3) oleic acid replaces ALA diet (ORAD) [7% SFAs, 14% PUFAs (0.4% ALA); 12% MUFAs] (all percentages listed are of total kilocalories ). Serum collected after the run-in (baseline) and each diet period was analyzed for lipoprotein classes and subclasses (vertical auto profile), cholesterol efflux, and PCSK9. Linear mixed models were used for data analysis. RESULTS: Compared with the ORAD, total cholesterol (mean ± SEM -8.9± 2.3 mg/dL; -5.1%; P < 0.001), non-HDL cholesterol (-7.4 ± 2.0 mg/dL; -5.4%; P = 0.001), and LDL cholesterol (-6.9 ± 1.9 mg/dL; -6.5%; P = 0.001) were lower after the WD; no other pairwise differences existed. There were no between-diet differences for HDL-cholesterol or LDL-cholesterol subclasses. Lipoprotein(a) [Lp(a)], cholesterol efflux, and PCSK9 were unchanged after the diets. CONCLUSIONS: In individuals at risk of CVD, replacement of SFAs with unsaturated fats from walnuts or vegetable oils improved lipid/lipoprotein classes, including LDL-cholesterol, non-HDL cholesterol, and total cholesterol, without an increase in Lp(a). These improvements were not explained by changes in cholesterol efflux capacity or PCSK9. This trial was registered at clinicaltrials.gov as NCT01235832.

Rubber seed oil supplementation enriches n-3 polyunsaturated fatty acids and reduces cholesterol contents of egg yolks in laying hens.

The experiment was conducted to evaluate the effects of five rubber seed oil (RSO) levels (0, 1%, 2%, 4%, and 6%) on hens laying performance, egg quality, and yolks fatty acid composition and cholesterol contents. Three hundred and sixty 30-week-old Lohmann Brown laying hens were allotted to 5 groups. The results showed that the egg production was increased in 4% RSO group (P < 0.05), but egg quality parameters and the contents of dry matter, lipid, and protein in yolks were not influenced among treatments (P > 0.05). Yolk cholesterol contents were reduced in RSO supplemental groups (P < 0.05). The concentration of total n-3 PUFA in yolks increased gradually while the ratio of n-6/n-3 decreased gradually with increasing dietary RSO levels (P < 0.001). In conclusion, dietary RSO supplementation increased yolk n-3 PUFA levels, improved yolk color, and reduced yolk cholesterol contents without negative influence on laying performance parameters.

Rubber seed oil and flaxseed oil supplementation alter digestion, ruminal fermentation and rumen fatty acid profile of dairy cows.

Rubber seed oil (RO) that is rich in polyunsaturated fatty acids (FA) can improve milk production and milk FA profiles of dairy cows; however, the responses of digestion and ruminal fermentation to RO supplementation in vivo are still unknown. This experiment was conducted to investigate the effect of RO and flaxseed oil (FO) supplementation on nutrients digestibility, rumen fermentation parameters and rumen FA profile of dairy cows. Forty-eight mid-lactation Holstein dairy cows were randomly assigned to one of four treatments for 8 weeks, including basal diet (CON) or the basal dietary supplemented with 4% RO, 4% FO or 2% RO plus 2% FO on a DM basis. Compared with CON, dietary oil supplementation improved the total tract apparent digestibility of DM, neutral detergent fibre and ether extracts ( P < 0.05). Oil treatment groups had no effects on ruminal digesta pH value, ammonia N and microbial crude protein ( P > 0.05), whereas oil groups significantly changed the volatile fatty acid (VFA) profile by increasing the proportion of propionate whilst decreasing total VFA concentration, the proportion of acetate and the ratio of acetate to propionate ( P < 0.05). However, there were no differences in VFA proportions between the three oil groups (P > 0.05). In addition, dietary oil supplementation increased the total unsaturated FA proportion in the rumen by enhancing the proportion of trans-11 C18:1 vaccenic acid (VA), cis-9, trans-11 conjugated linoleic acid (CLA) and α-linolenic acid (ALA) ( P < 0.05). These results indicate that dietary supplementation with RO and FO could improve nutrients digestibility, ruminal fermentation and ruminal FA profile by enhancing the VA, cis-9, trans-11 CLA and ALA composition of lactating dairy cows. These findings provide a theoretical basis for the application of RO in livestock production.

Gene expression profile following an oral unsaturated fat load in abdominal obese subjects.

PURPOSE: Our aim was to evaluate the postprandial effect of an oral fat load test (OFLT) rich in unsaturated fatty acids on gene expression profile in peripheral blood mononuclear cells (PBMC) from subjects with abdominal obesity as an insulin resistance model and controls. METHODS: A total of 20 controls and 20 abdominal obese patients were studied. Metabolic parameters and oxidative stress markers were measured with standardized protocols. The whole gene expression at fasting state and after the OFLT (0, 4 and 8 h) was analysed using human HT-12-v4 expression beadchips, from Illumina. RESULTS: We found a significant decrease in plasma glucose, insulin and oxidative stress markers in abdominal obese patients and controls. We found beneficial metabolic postprandial gene expression in three genes: FKBP5, DDIT4 and DHRS9. Following an OFLT, the postprandial mRNA expression of FKBP5, and DDIT4 was downregulated while that of DHRS9 was overexpressed, both in nondiabetic normolipidemic subjects and in insulin-resistant subjects with abdominal obesity. CONCLUSIONS: Our results suggest that an OFLT rich in unsaturated fatty acids downregulates the expression of FKBP5, coding for the glucocorticoid receptor pathway, and that of DDIT4, involved in the oxidative stress response. These changes could favourably influence the insulin resistance and oxidative stress status in the postprandial state.

Replacement of Refined Starches and Added Sugars with Egg Protein and Unsaturated Fats Increases Insulin Sensitivity and Lowers Triglycerides in Overweight or Obese Adults with Elevated Triglycerides.

Background: Hypertriglyceridemia is a common condition in the United States and is often associated with other metabolic disturbances, including insulin resistance, metabolic syndrome, and a predominance of small dense LDL particles.Objective: The objective of this trial was to evaluate the effects of a combination of egg protein (Epro) and unsaturated fatty acids (UFAs) substituted for refined starches and added sugars on insulin sensitivity (primary outcome) and other cardiometabolic health markers in overweight or obese adults with elevated triglyceride (TG) concentrations.Methods: Subjects with elevated TG concentrations were given test foods prepared by using Epro powder (∼8% of energy) and vegetable oil (∼8% of energy; Epro and UFA condition) or test foods prepared by using refined starch and sugar (∼16% of energy; carbohydrate condition) in a randomized, double-blind, controlled-feeding, crossover trial (3 wk/condition, 2-wk washout). The Matsuda insulin sensitivity index (MISI), fasting lipids, and other cardiometabolic health markers were assessed at baseline and the end of each diet condition. Responses were compared by using repeated-measures ANCOVA.Results: Twenty-five participants [11 men, 14 women; mean ± SEM: age, 46.3 ± 2.4 y; body mass index (in kg/m2), 31.8 ± 1.0] with a median (interquartile range limits) fasting serum TG concentration of 173 mg/dL (159, 228 mg/dL) completed the trial. The MISI value increased 18.1% ± 8.7% from baseline during the Epro and UFA condition and decreased 5.7% ± 6.2% from baseline during the carbohydrate condition (P < 0.001). The disposition index increased 23.8% ± 20.8% during the Epro and UFA condition compared with a decrease of 16.3% ± 18.8% during carbohydrate (P = 0.042) and LDL peak particle size increased 0.12 nm (-0.12, 0.28 nm) with Epro and UFA compared with a decrease of 0.15 nm (-0.33, 0.12 nm) with carbohydrate (P = 0.019). TG and VLDL cholesterol concentrations were lowered by 18.5% (-35.7%, -6.9%) and 18.6% (-34.8%, -7.4%), respectively, after the Epro and UFA condition and by 2.5% (-13.4%, 17.0%) and 3.6% (-12.5%, 16.2%), respectively, after the carbohydrate diet condition (P < 0.002).Conclusions: The replacement of refined carbohydrates with a combination of Epro and UFA increased the MISI value and altered several markers of cardiometabolic health in overweight or obese adults with elevated TG concentrations. This trial was registered at clinicaltrials.gov as NCT02924558.

Unsaturated Oral Fat Load Test Improves Glycemia, Insulinemia and Oxidative Stress Status in Nondiabetic Subjects with Abdominal Obesity.

AIMS: To evaluate the changes in glycemia, insulinemia, and oxidative stress markers during an oral fat load test in nondiabetic subjects with abdominal obesity and to analyze the association between postprandial oxidative stress markers and postprandial glucose and insulin responses. METHODS: We included 20 subjects with abdominal obesity (waist circumference > 102 cm for men and > 88 cm for women) and 20 healthy lean controls (waist circumference < 102 cm for men and < 88 cm for women). After 12 hours of fasting we performed a standardized fat load test (0-8 hours) with supracal® (50 g/m2). We determined metabolic parameters, oxidized and reduced glutathione, and malondialdehyde. RESULTS: In both groups, insulin, HOMA, oxidized/reduced glutathione ratio, and malondialdehyde significantly decreased in the postprandial state after the OFLT. All these parameters were significantly higher in the abdominal obesity group at baseline and during all the postprandial points, but the reduction from the baseline levels was significantly higher in the abdominal obesity group. CONCLUSION: Unsaturated fat improves insulin resistance and oxidative stress status. It is possible that a consumption of unsaturated fat could be beneficial even in subjects with abdominal obesity in postprandial state.

Dietary lipid unsaturation influences survival and oxidative modifications of an amyotrophic lateral sclerosis model in a gender-specific manner.

The implication of lipid peroxidation in neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) derive from high abundance of peroxidation-prone polyunsaturated fatty acids in central nervous system and its relatively low antioxidant content. In the present work, we evaluated the effect of dietary changes aimed to modify fatty acid tissular composition in survival, disease onset, protein, and DNA oxidative modifications in the hSODG93A transgenic mice, a model of this motor neuron disease. Both survival and clinical evolution is dependent on dietary fatty acid unsaturation and gender, with high unsaturated diet, leading to loss of the disease-sparing effect of feminine gender. This was associated with significant increases in protein carbonyl and glycoxidative modifications as well as non-nuclear 8-oxo-dG, a marker of mitochondrial DNA oxidation. Comparison of these data with γH2AX immunostaining, a marker of DNA damage response, suggests that the highly unsaturated diet-blunted mitochondrial-nuclear free radical dependent crosstalk, since increased 8-oxo-dG was not correlated with increased DNA damage response. Paradoxically, the highly unsaturated diet led to lower peroxidizability but higher anti-inflammatory indexes. To sum up, our results demonstrate that high polyunsaturated fatty acid content in diets may accelerate the disease in this model. Further, these results reinforce the need for adequately defining gender as a relevant factor in ALS models, as well as to use structurally characterized markers for oxidative damage assessment in neurodegeneration.

Oxidative stress and antioxidant enzyme values in lymphomonocytes after an oral unsaturated fat load test in familial hypercholesterolemic subjects.

Oxidative stress (OS) has been observed in conditions affecting the cardiovascular system. Familial hypercholesterolemia (FH) is associated with an increased risk of premature coronary heart disease. In the postprandial state, circulating lipids and lipoproteins can modulate OS status. Our aim was to study the response of lymphomonocyte OS status and reactive oxygen species by-products after an oral unsaturated fat load test (OFLT) in those with FH and to compare this response with that obtained in normolipidemic, normoglycemic subjects. We studied 12 patients with FH and 20 healthy controls. In both groups, lymphomonocyte, oxidized/reduced glutathione ratio, and malondialdehyde were determined at baseline and at 2, 4, 6, and 8 hours after an OFLT. Fasting urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine and isoprostane were measured using standard procedures. In both groups, oxidized/reduced glutathione ratio and malondialdehyde significantly decreased in the postprandial state after the OFLT. Both parameters were significantly higher in the FH group at baseline and during all the postprandial points, but the reduction from the baseline levels was significantly higher in the FH group than in the control group. Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine was significantly increased in the FH group compared with the healthy control group, indicating a higher fasting OS status. We conclude that subjects with FH exhibited OS levels that were higher than in controls before and after an OFLT, but the improvement in the OS status after the unsaturated fat load was significantly higher in subjects with FH.

Macadamia nut consumption modulates favourably risk factors for coronary artery disease in hypercholesterolemic subjects.

Macadamia nuts are rich source of monounsaturated fats (oleic and palmitoleic acids) and contain polyphenol compounds, therefore, their consumption can be expected to impart health benefits to humans. This study was conducted to examine the effects of consuming macadamia nuts in hypercholesterolemic male individuals on plasma biomarkers of oxidative stress, coagulation and inflammation. Seventeen hypercholesterolemic male subjects were given macadamia nuts (40-90 g/day), equivalent to 15% energy intake, for a period of 4 weeks. As expected, monounsaturated fatty acids (16:1n-7, 18:1n-9 and 20:1n-9) were elevated in the plasma lipids of all volunteers following intervention with macadamia nuts. Plasma markers of inflammation (leukotriene, LTB(4)) and oxidative stress (8-isoprostane) were significantly lower (1,353 +/- 225 vs. 1,030 +/- 129 pg/mL and 876 +/- 97 vs. 679 +/- 116 pg/mL, respectively) within 4 weeks following macadamia nut intervention. There was a non-significant (23.6%) reduction in the plasma TXB(2)/PGI(2) ratio following macadamia nut consumption. This study demonstrates, for the first time, that short-term macadamia nut consumption modifies favourably the biomarkers of oxidative stress, thrombosis and inflammation, the risk factors for coronary artery disease, despite an increase in dietary fat intake. These data, combined with our previous results on cholesterol-lowering effects of macadamia nuts, suggest that regular consumption of macadamia nuts may play a role in the prevention of coronary artery disease.

Effects of conjugated linoleic acid supplementation on blood lipids and adiposity of rats fed diets rich in saturated versus unsaturated fat.

Conjugated linoleic acid (CLA) may decrease adiposity and improve blood lipid profiles under some conditions. The goal of this study was to determine the effects of CLA supplementation on blood lipid profiles and adiposity of rats fed a diet containing a primarily saturated fat versus a diet containing a primarily unsaturated fat. Twenty-eight male Sprague-Dawley rats were randomly assigned to one of four diets containing coconut oil, coconut oil with CLA, corn oil or corn oil with CLA. After 28 days, blood was collected and serum concentrations of total cholesterol (TC), HDL-cholesterol (HDL-C), and triacylglycerols (TG) were assessed. Food intake, body weights, and epididymal fat pads were measured. No significant differences (p>0.05) were noted among groups for amount of food consumed, weight gained, food efficiency ratio or serum TG concentrations. TC concentrations were lower (p<0.05) in the CLA-supplemented rats that were fed coconut oil but not those consuming corn oil. Serum HDL-C was lower (p<0.05) in rats consuming corn oil but was not significantly different (p>0.05) for CLA supplemented groups. Epididymal fat pads weighed significantly more (p<0.05) in the coconut oil fed group compared to the corn oil fed group, but there was no significant difference (p>0.05) between the corn oil and coconut oil + CLA group. Overall, this study suggests that CLA is more beneficial for control of blood lipids and adiposity when supplemented to a diet rich in saturated versus unsaturated fat.

Serum aminopeptidase A activity of mice is related to dietary fat saturation.

A high intake of monounsaturated fat has been proposed to be a dietary factor that can decrease the incidence of cardiovascular disease and hypertension. In addition, increasing dietary fat saturation has been shown to increase plasma total cholesterol and elevate systolic and diastolic blood pressures. We demonstrated previously that cholesterol selectively increases in vitro aminopeptidase A activity, which is related to angiotensin metabolism. In this study, we investigated the effect of different degrees of dietary fatty acid saturation on serum aminopeptidase activities in vivo. Serum total cholesterol concentrations were also measured. Five groups of male Balb/C mice were fed for 10 wk diets containing 2.4 g/100 g of sunflower oil, fish oil, olive oil, lard or coconut oil. We measured alanyl-, arginyl-, cystinyl-, pyroglutamyl-, aspartyl- and glutamyl-specific aminopeptidase activities using arylamides as substrates. Serum total cholesterol levels were higher in mice fed diets containing saturated oils (lard and coconut) than in those consuming sunflower oil, which is unsaturated. Two of the serum aminopeptidase A activities (aspartyl and glutamyl aminopeptidase) increased progressively with the degree of saturation of the dietary fatty acids; activities were significantly greater in mice fed coconut oil than in those fed sunflower or fish oil. Therefore, the substrates hydrolyzed by this activity as well as their functions may be similarly affected. These results may have some implication for the treatment of cardiovascular disease.

Effect of dietary fats differing in degree of unsaturation on gene expression in rat adipose tissue.

To test the possibility that the type of dietary fat affects the expression of proteins involved in adipose tissue metabolism, levels of mRNA for lipoprotein lipase, leptin, glucose transporter 4, and uncoupling protein in adipose tissues were compared among rats fed a low-fat diet (2% safflower oil), and high-fat diets containing 20% saturated fat (palm oil) or unsaturated fat rich in linoleic acid (safflower oil) for 3 weeks. High-fat diets decreased the lipoprotein lipase mRNA level in epididymal but not in perirenal white adipose tissue, but increased it in brown adipose tissue. Leptin gene expression in perirenal white adipose tissue was significantly higher in rats fed high-fat diets than in those fed a low-fat diet. High-fat diets failed, however, to alter this parameter in epididymal white adipose tissue and interscapular brown adipose tissue. mRNA levels of glucose transporter 4, both in epididymal and perirenal white adipose tissues, were lower in rats fed high-fat diets than in those fed a low-fat diet. Uncoupling protein gene expression in interscapular brown adipose tissue was 2-3 times higher in rats fed high-fat diets than in those fed a low-fat diet. The abundance of mRNAs for lipoprotein lipase, leptin, glucose transporter 4 and uncoupling protein was, however, comparable between rats fed diets high in safflower and palm oil. We concluded that the high-fat diet influences gene expression of adipose tissue in a site-specific manner. The difference in the degree of unsaturation of dietary fats is rather irrelevant in modifying the level of mRNAs for proteins related to energy metabolism and expenditure in adipose tissue.

Cholesterol-lowering nature of unsaturated fat in rats may be due to its inability to increase hepatic iron.

The present investigation was conducted to determine whether the cholesterol-raising properties of saturated fat and cholesterol-lowering properties of unsaturated fat are associated with levels of hepatic iron. The magnitude of hepatic iron retention was manipulated by feeding rats diets that were either copper-deficient or -adequate, iron-adequate or -supplemented, and contained either beef tallow or corn oil. Weanling male Sprague-Dawley rats were randomly divided into eight dietary groups according to the type of dietary fat (beef tallow or corn oil) and level of dietary copper (0.74 or 6.9 microg Cu/g diet) or iron (44.4 or 86.7 microg Fe/g diet). Beef tallow and copper deficiency alone increased hepatic iron levels, which in turn were associated with increased plasma cholesterol. When the three dietary factors were combined, ie, iron, beef tallow, and copper deficiency, they induced the highest magnitude of hepatic iron retention, which in turn was associated with the highest concentration of plasma cholesterol. In contrast, when hepatic iron retention was not increased, such as by feeding a diet containing corn oil or by consumption of a copper-adequate diet, plasma cholesterol was not elevated. Based on these data, it is suggested that nutrients that have the ability to increase hepatic iron have the potential to increase plasma cholesterol.

Hydrogenated fat high in trans monoenes with an adequate level of linoleic acid has no effect on prostaglandin synthesis in rats.

Our study was designed to determine whether hydrogenated fat high in trans monoenes concentration affected prostaglandin synthesis. Corn oil (CO), butter (B), hydrogenated vegetable oil (HF) and coating fat (CF) were used in this study. These fats were fed to rats for 10 wk at 10 g/100 g diet. The phospholipid (PL) fatty acid content of platelets, aorta and heart was determined by gas liquid chromatography, and the in vitro aorta production of prostacyclin (PGI2) from exogenous or endogenous arachidonic acid (AA) was measured using the radioimmuno-assay (RIA) method. Serum thromboxane B2 (TXB2) released by platelets as thromboxane A2 (TXA2) during incubation of whole blood was also measured by this method. In the group fed CF, AA was significantly lower in the PL of aorta, platelet and heart, and the ratio 20:3(n-9)/20:4(n-6) was greater than in the groups fed CO, B or HF, indicating that the group fed CF was essential fatty acid (EFA) deficient. Although AA was significantly lower in the aorta and platelet PL of the group fed HF compared to the group fed CO, that difference did not affect the amounts of PGI2 or TXB2 produced in these groups. The group fed CF had significantly less PGI2 and TXB2 released by aorta and platelets than the other groups. This was the result of the reduced level of AA and the presence of higher amounts of 20:3(n-9) acid in the PL, which might act as a competitive inhibitor for cyclooxygenase. The aortic production of PGI2 from exogenous AA did not differ among the groups indicating that prostaglandin synthetase was not affected by the dietary fat. We conclude that the consumption of hydrogenated fats high in trans 18:1 acids with adequate amount of linoleic acid had no effect on the amount of thromboxane or prostacyclin produced by platelet or aorta in vitro.

Protein carbonyl content roughly reflects the unsaturation of lipids in muscle but not in other tissues of stroke-prone spontaneously hypertensive strain (SHRSP) rats fed different fats and oils.

We examined in vivo the effect of dietary fats and oils with different peroxidizability on protein carbonyl content, the presumed index of free radical-mediated protein oxidation. For 15.6 months, SHRSP (stroke-prone spontaneously hypertensive strain) rats were fed a diet supplemented with lard, safflower oil, perilla oil or fish oil/soybean oil, the peroxidizability of which increases in this order. The peroxidizability of tissue lipids was positively correlated with the protein carbonyl content in skeletal muscle, but not in the brain, heart or liver. The protein carbonyl content in the lard group was higher in the brain and liver compared to the other dietary groups. These results contradict the concept that long-term feeding of easily autoxidizable fatty acids allows the accumulation of lipid peroxides to accelerate the development of the free radical diseases, and suggest that tissue protein carbonyl content is not a simple reflection of autoxidizability-related lipid peroxidation but is also influenced by other biochemical processes.

The relationship between altered membrane composition, eicosanoids and TNF-induced IL1 and IL6 production in macrophages of rats fed fats of different unsaturated fatty acid composition.

The study investigated the changes in individual molecular species in PE and the effects of a variety of dietary fats with varying proportions of saturated and unsaturated fatty acids on membrane composition, eicosanoid production and cytokine production in thioglycollate-elicited rat macrophages. The data obtained indicates that the greatest degree of modulation by dietary fats on cytokine production was observed after 8 weeks feeding and at this time, the total diacyl species containing linoleic acid (18:2 n-6) and arachidonic acid (20:4 n-6) at the sn-2 position related in a curvilinear fashion to total 18:2 n-6 intake and that IL1 and IL6 production related in a curvilinear fashion to the total diacyl species with 20:4 and 18:2 at the sn-2 position. After 4 weeks of feeding, fish and olive oils enhanced production of IL6 and LTB4, however, while IL1 production, after 8 weeks of dietary treatment, was greatest from macrophages of animals fed corn and olive oils, PGE2 production was greatest in the former group and LTB4 production in the latter. Thus an eicosanoid effect may explain the modulatory influence of olive oil and IL1 production but, cannot explain the effect of corn oil on production of the cytokine. The data from the present study provides some insight into how dietary fats could provide therapy for conditions in which inflammatory cytokines are implicated.

Effects of dietary polyunsaturated fat on ethanol-induced Ito cell activation.

Ito cells, vitamin A-storing perisinusoidal cells, are believed to undergo myofibroblastic transformation in liver fibrogenesis. Our previous studies have shown that a diet high in polyunsaturated fat was key for induction of experimental alcoholic liver fibrosis. To investigate the cellular basis for this fibrogenic effect of a high-fat diet, we analyzed the content of vitamin A and cellular retinol binding protein (CRBP), the steady-state mRNA levels of procollagen-alpha1(I), transforming growth factor-beta1 (TGF-beta1), interleukin-6 (IL-6), and smooth muscle alpha-actin (alpha-SM) in freshly isolated Ito cells from rats given isocaloric amounts of ethanol and a low- or high-fat diet. After 10 wk, the Ito cell content of retinyl palmitate was severely reduced in both the high- and low-fat diet-ethanol-fed animals to 13-17% of those measured in respective pair-fed controls. On the other hand, the content of CRBP was reduced in the high-fat-ethanol rats but not in the low-fat-ethanol group. The cells from the high-fat-ethanol but not low-fat ethanol rats showed an 18-fold increase in procollagen-alpha1(I) mRNA at 17 wk, which was accompanied by 2.8- and 2.3-fold enhancement of TGF-beta1 and alpha-SM transcripts. IL-6 mRNA was not detected in the cells from any groups. These results demonstrate 1) myofibroblastic activation of Ito cells is evident in rats given a high-fat diet and ethanol but not in the low-fat-ethanol animals; 2) vitamin A depletion of Ito cells is the early and general effect of chronic ethanol intake but does not necessarily predict subsequent myofibroblastic activation; 3) reduced CRBP level is more closely associated with the subsequent cellular activation seen under the high-fat-ethanol regimen; and 4) IL-6 is not expressed in vivo by Ito cells from either normal livers or livers with alcoholic liver fibrosis.

Dietary cholesterol and fat saturation effects on plasma esterified and unesterified cholesterol in selected lines of Japanese quail females.

Three lines of Japanese quail females, randombred controls (CL), high response (HL), and low response (LL) lines, selected for plasma total cholesterol for 18 generations, were fed all-plant-source, nonatherogenic diets to which 0 or .5% cholesterol were added from 6 to 18 wk of age. In all three lines, plasma cholesterol increased when cholesterol was fed; however, responses were greater in the HL than in the LL line, with CL intermediate. In a second experiment, females of the three lines were fed, from 6 to 14 wk of age, four isocaloric, isonitrogenous plant-source diets to which were added: 1) 10% glucose monohydrate (cerelose); 2) 10% cerelose + .1% cholesterol; 3) 4% corn oil; or 4) 4% coconut oil. Baseline data obtained before feeding experimental diets indicated that the HL had significantly higher plasma total, esterified (EC) and unesterified (UEC) cholesterol than LL and that nonovulating females had higher concentrations of esterified cholesterol than ovulating females. Diets used did not affect cholesterol fractions in the ovulating females, although there were significant differences among lines. Dietary cholesterol significantly increased the ratio of EC to UEC. Sclerotic lesion scores were higher in the HL than the LL birds and in birds fed the coconut oil diet.