A diet containing myristoleic plus palmitoleic acids elevates plasma cholesterol in young growing swine

The objective of this study was to test the effect of a novel fatty acid mixture, enriched with myristoleic and palmitoleic acids, on plasma lipoprotein cholesterol concentrations. Weanling pigs were assigned to one of six groups and each group received a diet differing in fatty acid composition. Diets were fed for 35 days and contained 10 g added cornstarch/100 g (to provide baseline data) or 10 g added fatty acids/100 g. For those diets containing added fatty acids, extracted lipids contained 36% myristoleic plus palmitoleic acid combined (14∶1/16∶1 diet), 52% palmitic acid (16∶0 diet), 51% stearic acid (18∶0 diet), 47% oleic acid (18∶1 diet), or 38% linoleic acid (18∶2 diet). Witht the exception of the cornstarch diet, all diets contained approximately 30% myristic acid. There were no significant differences in weight gain across treatment groups (P=0.22). All diets caused a significant increase in triglycerides and in total, low density lipoprotein, high density lipoprotein, and very low density lipoprotein cholesterol. The increase in total plasma cholesterol from pretreatment values was greatest in pigs fed the 14∶1/16∶1 and 18∶1 diets. However, the increase in low density lipoprotein cholesterol from the pretreatment concentration was greatest in the 14∶1/16∶1-fed pigs. Increases in very low density lipoprotein cholesterol above pretreatment concentrations were lowest in 16∶0-fed pigs and greatest in 18∶1-fed pigs. Dietary fatty acids elicited changes in plasma fatty acids which generally were reflective of the diets, although the 18∶0 diet did not alter plasma fatty acid concentrations and the 16∶0 diet increased plasma 16∶0 only at the end of the study. These results demonstrated that the combination of myristoleic plus palmitoleic acids increased plasma cholesterol in young pigs, suggesting that fatty acid chain length, rather than degree of unsaturation, is primarily responsible for the effects of fatty acids on circulating lipoprotein cholesterol concentrations.     

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.     

Effect of a modified milk fat and calcium in purified diets on cholesterol metabolism in hamsters

Modification of milk fat both by partially replacing saturated FA with oleic acid (18∶1) and by increasing calcium intake independently reduces plasma cholesterol. Whether modification of both factors together would synergistically reduce plasma cholesterol is unknown. Seventy-two male golden Syrian hamsters were separated into four diet treatment groups (n=18/group) and fed ad libitum for 7 wk. Diets contained either modified milk fat (MMF) or regular milk fat (RMF) with either 0.5% (MMF and RMF) or 1.3% calcium (w/w) (MMFC and RMFC). All diets contained 11% test fat, 4% soybean oil, and 0.15% cholesterol (w/w). During the last week, feces were collected for three consecutive days for analysis of fecal FA, cholesterol, and calcium excretion. Overnight-fasted animals were sacrificed, and plasma and livers were collected for lipid analysis. Neither MMF nor additional calcium significantly affected plasma lipids. However, significant interactions existed between MMF and additional calcium for the ratio of LDL cholesterol to HDL cholesterol (LDL/HDL), indicating that increased calcium intake reduced this ratio only in RMF animals. In addition, MMF reduced LDL/HDL relative to RMF. MMF significantly increased hepatic total and esterified cholesterol. Additional calcium significantly increased fecal calcium and saturated FA (SFA) excretion, whereas MMF significantly reduced SFA excretion. RMFC induced the highest excretion of 16∶0 among all groups. Replacement of SFA with 18∶1 in the MMF reduced the impact of high calcium on LDL/HDL. Additional calcium reduced LDL/HDL only in the presence of RMF, which may be achieved through an increased excretion of 16∶0.     

The effect of dietary fat level and quality on plasma lipoprotein lipids and plasma fatty acids in normocholesterolemic subjects

This study examined the effect on the plasma lipids and plasma phospholipid and cholesteryl ester fatty acids of changing from a typical western diet to a very low fat (VLF) vegetarian diet containing one egg/day. The effect of the addition of saturated, monounsaturated or polyunsaturated fat (PUFA) to the VLF diet was also examined. Three groups of 10 subjects (6 women, 4 men) were fed the VLF diet (10% energy as fat) for two weeks, and then in the next two weeks the dietary fat in each group was increased by 10% energy/week using butter, olive oil or safflower oil. The fat replaced dietary carbohydrate. The VLF diet reduced both the low density lipoprotein (LDL)-and high density lipoprotein (HDL)-cholesterol levels; addition of the monounsaturated fats and PUFA increased the HDL-cholesterol levels, whereas butter increased the cholesterol levels in both the LDL- and HDL-fractions. The VLF diet led to significant reductions in the proportion of linoleic acid (18∶2ω6) and eicosapentaenoic acid (20∶5ω3) and to increases in palmitoleic (16∶1), eicosatrienoic (20∶3ω6) and arachidonic acids (20∶4ω6) in both phospholipids and cholesteryl esters. Addition of butter reversed the changes seen on the VLF diet, with the exception of 16∶1, which remained elevated. Addition of olive oil resulted in a significant rise in the proportion of 18∶1 and significant decreases in all ω3 PUFA except 22∶6 compared with the usual diet. The addition of safflower oil resulted in significant increases in 18∶2 and 20∶4ω6 and significant decreases in 18∶1, 20∶5ω3 and 22∶5ω3. These results indicate that the reduction of saturated fat content of the diet (<6% dietary energy), either by reducing the total fat content of the diet or by exchanging saturated fat with unsaturated fat, reduced the total plasma cholesterol levels by approximately 12% in normocholesterolemic subjects. Although the VLF vegetarian diet reduced both LDL- and HDL-cholesterol levels, the long-term effects of VLF diets are unlikely to be deteterious since populations which habitually consume these diets have low rates of coronary heart disease. The addition of safflower oil or olive oil to a VLF diet produced favorable changes in the lipoprotein lipid profile compared with the addition of butter. The VLF diets and diets rich in butter, olive oil or safflower oil had different effects on the 20 carbon eicosanoid precursor fatty acids in the plasma. This suggests that advice on plasma lipid lowering should also take into account the effect of the diet on the fatty acid profile of the plasma lipids.     

Natural abundance stable carbon isotope evidence for the routing and <Emphasis Type="Italic">de novo</Emphasis> synthesis of bone FA and cholesterol

This research reported in this paper investigated the relationship between diet and bone FA and cholesterol in rats raised on a variety of isotopically controlled diets comprising 20% C₃ or C₄ protein (casein) and C₃ and/or C₄ nonprotein or energy (sucrose, starch, and oil) macronutrients. Compoundspecific stable carbon isotope analysis (δ¹³C) was performed on the FA (16∶0, 18∶0, 18∶1, and 18∶2) and cholesterol isolated from the diet (n=4) and bone (n=8) of these animals. The dietary signals reflected by the bone lipids were investigated using linear regression analysis. δ¹³C values of bone cholesterol and stearic (18∶0) acid were shown to reflect whole-diet δ¹³C values. whereas the δ¹³C values of bone palmitic (16∶0), oleic (18∶1), and linoleic (18∶2) acids reflected dietary FA δ¹³C values. Dietary signal differences are a result of the balance between direct incorporation (or routing) and de novo synthesis of each of these bone lipids. Estimates of the degree of routing of these bone lipids gleaned from correlations between Δ¹³C _dlipid-wdiet (δ¹³C_{diet lipid}-δ¹³C_{whole diet}) spacings and Δ¹³C _blipid-wdiet (δ¹³C_{bone lipid}-δ¹³C_{whole diet} fractionations demonstrated that the extent of routing, where 18∶2>16∶0>18∶1>18∶0>cholesterol, reflected the relative abundances of these lipids in the diet. These findings provide the basis for more accurate insights into diet when the δ¹³C analysis of bone fatty FA or cholesterol is employed.     

Effect of apolipoprotein E polymorphism on serum lipoprotein response to saturated fatty acids

This report summarizes two studies which investigated the effects of apolipoprotein E (apoE) polymorphism on the serum total cholesterol (TC) and lipoprotein cholesterol responses to 8∶0+10∶0 and 12∶0 diets (Study I) and 14∶0, 16∶0, and 18∶0 diets (Study II). Eighteen healthy premenopausal women (3 apoE 3/2, 12 apoE 3/3, 3 apoE 4/3) in study I and another 18 healthy premenopausal women (4 apoE 3/2, 10 apoE 3/3, 3 apoE 4/3, 1 apoE 4/2) in study II consumed a baseline diet providing 40 en% total fat, 11 en % 18∶2, 15 en% 18∶1, 11.5 en% saturated fat for the first week of each 5-wk period. The experimental diets for both studies provided 40 3n% total fat, 13–14 en% as one of five test saturated fatty acids (SFA), 14–16 en% 18∶1, and 3–4 en% 18∶2. Analysis by apoE phenotypes showed that both the 8∶0+10∶0 diet and the 12∶0 diet in Study Linduced significant increases in serum TC in subjects with different apoE phenotypes with the exception of apoE 3/2 in the medium-chain triglyceride group. In contrast, in Study II, individuals with apoE 4/3 consuming the 14∶0 diet showed significant increases in serum TC, high density lipoprotein-cholesterol (HDL-C), and HDL2-C, but the same subjects consuming the 16∶0 diet showed significant increases in serum TC and low density lipoprotein-cholesterol. The findings from both studies indicated serum lipoprotein responses to SFA were different and the variation of responsiveness may be regulated, at least in part, by apoE polymorphism, especially when 14∶0, 16∶0, or 18∶0 was consumed.     

Plasma lipids are affected similarly by dietary lauric or palmitic acid in gerbils and monkeys

To compare the relative impact of dietary lauric acid (12∶0) and palmitic acid (16∶0) on plasma lipids, two fat-sensitive species, Mongolian gerbils and cebus monkeys, were fed cholesterol-free, purified diets enriched with either 12∶0-rich or 16∶0-rich fats, while all other fatty acids were held constant by selective blending of up to five natural fats or oils. The two gerbil diets (40 en% from fat) allowed for an 8 en% exchange between 12∶0 and 16∶0, and the monkey diets (31 en% from fat) allowed for 6 en% exchange beteen these two fatty acids. Eight gerbils received the diets for eight weeks, and 12 cebus monkeys were fed each diet in a cross-over design for up to 22 wk. Both diets resulted in similar plasma cholesterol, triglyceride, and high density lipoprotein cholesterol concentrations within each species. Additionally, separation of cebus lipoproteins by discontinuous density-gradient ultracentrifugation failed to show any dietary differences in concentration or composition of the three major lipoprotein classes (d<1.019, 1.019–1.055, and 1.055–1.168 g/mL). Thus, in two species sensitive to manipulations in dietary fat while consuming cholesterol-free diets, 16∶0 was not hypercholesterolemic relative to 12∶0. Based on a paper presented at the PORIM International Palm Oil Congress (PIPOC) held in Kuala Lumpur, Malaysia, September 1993.     

Hepatic lipid characteristics and histopathology of laying hens fed CLA or n−3 fatty acids

The effect of dietary CLA and n−3 PUFA on hepatic TAG accumulation, histopathology, and FA incorporation in lipid classes by laying chickens was investigated. One hundred twenty 30-wk-old single-comb white leghorn laying hens were distributed randomly to four treatments (3 replications of 10 birds) and were fed diets containing CLA and animal fat (Diet I), 18∶3n−3 (Diet II), or long-chain n−3 FA (Diet III). A sunflower oil (n−6 FA)-based diet was the control. Feeding Diet I resulted in an increase in hepatic total lipids (P<0.05). The liver TAG content was 32.2, 18.9, 29.4, and 18.7 mg/g for hens fed Diet I, Diet II, Diet III, and the control diet, respectively (P<0.05). The serum TAG was lowest in bilds fed Diet II (P<0.05). Diet I resulted in an increase in the total number of fat vacuoles and lipid infiltration in hepatocytes (P<0.05). The number of cells with 75% or higher lipid vacuolation was observed only in birds fed Diet I. Feeding diets containing CLA resulted in an increase in the content of the c9,t11 CLA isomer in liver TAG and PC (P<0.05). No difference was observed in the CLA concentration of hepatic PE fractions. The content of DHA (22∶6n−3) was higher in the TAG, PC, and PE of hens fed Diet II and Diet III than Diet I and the control (P<0.05). Feeding CLA resulted in an increase in total saturated FA in the TAG and PC fractions (P<0.05). Long-term feeding of CLA in laying birds leads to an increase in liver TAG and may predispose birds to fatty liver hemorrhagic syndrome.     

Effect of exercise on the plasma nonesterified fatty acid composition of dogs and goats: Species with different aerobic capacities and diets

The goals of this study were to determine: (i) whether mammals mobilize particular nonesterified fatty acids (NEFA) preferentially during locomotion, (ii) if differences in aerobic capacity or diet can affect the pattern of NEFA mobilization and (iii) which individual NEFA are most representative of total NEFA concentration changes, to use them as tracers for turnover studies. Individual NEFA were measured in trained dogs and goats (VO₂max dog/VO₂max goat=2.2; where VO₂max=max-imal oxygen consumption) during treadmill exercise at 40 and 60% VO₂max. Important interspecies differences in individual NEFA concentrations could be attributed to differences in aerobic capacity. The more aerobic species (dog) had much higher plasma NEFA concentrations for all but one NEFA (18∶0), when compared with the low-aerobic species (goat). In addition, exercise caused a large increase in concentration of individual NEFA in the dogs, with the largest increases seen in 18∶1 (150% above resting values) and 16∶0 (60% increase), but it had no effect in goats. Therefore, the aerobic species has a much higher ability for mobilizing and transporting NEFA in plasma than its low-aerobic counterpart. Two NEFA accounted for more than half total plasma NEFA in both species, 18∶1 (about 35% total NEFA) and 16∶0 (20%). Calculation of variability in percent composition reveals that oleate and palmitate also closely reflect changes in total NEFA and are therefore the most appropriate tracers forin vivo kinetic studies in exercising mammals. Differences in diet and digestion physiology explained some differences in the plasma NEFA composition of the two species; this was reflected in the percent contributions of individual fatty acids to total NEFA: in dogs 18∶1>16∶0>18∶2>18∶0, while in goats 18∶1>16∶0>18∶0>18∶2. Also, only goats had 18∶3 (6% total NEFA), a fatty acid of plant origin, while only dogs had 16∶1 (7% total NEFA). Overall, however, the plasma NEFA composition of goats did not exactly reflect that of their diet due to preabsorptive modification of unsaturated fatty acids, while in dogs there was a good correlation between dietary and plasma NEFA.     

Low-fat diets do not lower plasma cholesterol levels in healthy men compared to high-fat diets with similar fatty acid composition at constant caloric intake

In most studies reporting the effects of high-fat (HF) and low-fat (LF) diets on human plasma fatty acids (FA) and lipoprotein levels, the design involved adding to the diet an oil that had an FA composition (FAC) very different from the FAC of the control diet. Thus, it is difficult to determine if simply reducing the fat content of the diet without changing the dietary FAC changes the tissue FAC or alters plasma lipid levels. In this study, we fed diets that contained either 22 or 39% of calories from fat, but had no differences in their FAC, for 50 d to a group (n=11) of healthy men (20–35 y). Thus, the polyunsaturated/saturated ratios (1.0) of the diets were identical as were the n−3/n−6 ratio and the monounsaturated-to-total fat ratios. The diets contained (wt% of total fat) approximately 28% saturated FA, 33% monounsaturatedcis-FA, 6% monounsaturatedtrans-FA, 22% n−6 polyunsaturated FA, and 7% n−3 polyunsaturated FA, and 4% other minor FA. The diets consisted of natural foods and were formulated to contain 16 en% protein, either 45 or 62 en% carbohydrate (CHO) and at least the recommended dailyallowance for all micronutrients. Both diets contained 360 mg of cholesterol per day. All subjects were given the HF diet for 20 d, and then six were placed on the LF and the other five remained on the HF diet for 50 d. The two groups were crossedover for the remaining 50 d of the study. The subjects' baseline total cholesterol level was 173 mg/dl, after 50 d on the HF diet it was 177 mg/dl and after 50 d on the LF diet, 173 mg/dl. The differences were not significant, and there were no significant changes in either the LDL or HDL cholesterol levels with either diet. Triglyceride levels, and consequently very low density lipoprotein levels, rose significantly on the LF, higher CHO diet compared to the levels found in the subjects on the HF diet (91.5 and 66.4 mg/dl respectively,P<0.002). The linoleic acid content of the plasma, platelets, and red blood cells was significantly (P<0.05) reduced in the LF diet compared to HF diet, without any obvious physiological effects. Hence, many earlier observations indicating reductions in plasma lipid levels when people are on LF diets may be due to changes in the FAC of the diet, not the reduction in fat calories.     

Vitamin E,cholesterol, and lipids during atherogenesis in rabbits

Rabbits were fed diets including cholesterol and 10% butterfat to determine whether polyunsaturated butter (9% 18∶2) would be less atherogenic than normal saturated butter (3% 18∶2) when fed for 12 weeks. The cholesterol diets alone, 0.5% or 2%, produced aortic plaque development, and plasma cholesterol increased 20 times, lipids increased 10 times, and vitamin E increased 5 times. The inclusion of both fat and cholesterol in the diet produced a synergistic effect, doubling these values to 40 times for cholesterol, 20 times for lipids, and 10 times for vitamin E. The higher circulating levels of cholesterol caused increased tissue levels of cholesterol. With 2% cholesterol and fat, liver and aorta cholesterol increased 10 times, heart 4 times, and muscle cholesterol 2 times. The lower 0.5% dietary cholesterol load was successful in limiting the amount of tissue cholesterol increase. Liver, aorta, heart, and muscle levels of cholesterol were only about half the concentration attained when 2% cholesterol was fed. It was concluded that there were no differences in plasma or tissue cholesterol, vitamin E, or atherosclerosis attributable to the polyunsaturated nature of the diet. The 10% butterfat diets alone, whether saturated or unsaturated, did not induce aortic plaques and did not increase blood or tissue cholesterol, lipids, or vitamin E. Our results suggest that the lipid mobilizing effect is mediated by cholesterol, probably by conversion to bile acids and a stimulation in intestinal absorption.     

The effect of alfalfa-corn diets on cholesterol metabolism and gallstones in prairie dogs

Cholesterol gallstones were present in prairie dogs fed alfalfa plus corn with and without exogenous cholesterol (0.4%). The diets fed to the animals for eight weeks contained alfalfa plus corn in fixed proportions of 50∶50, 85∶15 and 15∶85 (w/w). At sacrifice, all animals were healthy but had not gained weight; no deaths occurred during the experiment. Cholesterol gallstones were present in all groups. In the absence of exogenous cholesterol, the highest stone incidence was found in the animals which received the lowest fiber (highest corn) diets (alfalfa plus corn, 50∶50, 67%; alfalfa plus corn, 15∶85, 83%). Cholesterol gallstone incidence was 100% when exogenous cholesterol was added to the alfalfa plus corn diets (50∶50 and 15∶85). No pigment gallstones were detected in any animal. Liver and plasma cholesterol concentrations were highest in the animals receiving alfalfa plus corn (15∶85) plus 0.4% cholesterol (4.29 mg/g, and 356 mg/dl, respectively). These values were lowest in animals receiving 85% alfalfa plus 15% corn without cholesterol (2.19 mg/g and 88 mg/dl, respectively). Lithogenic indices were below 1.00 in all groups. Biliary bile acids were mainly amidates of cholic acid and chenodeoxycholic acid, with the former predominating. Thus, gallstones can be formed in prairie dogs in the absence of exogenous cholesterol; gallstone incidence is reduced by dietary fiber.     

Effects of dietary triolein and sunflower oil on insulin release and lipid metabolism in zucker rats

Obese and lean male Zucker rats were fed ad libitum on diets containing either 50 (L) or 200 (H) g/kg diet of either triolein (T) or sunflowerseed oil (S). The specific activity of the hepatic microsomal Δ9 desaturase enzyme was depressed in both lean and obese rats fed the HS diet compared with the other three diets. The fatty acid composition of liver and subcutaneous white adipose tissue lipids were consistent with a lower Δ9 desaturation activity in rats fed the H diets, particularly for the HS diet. In both genotypes, microsomal Δ9 desaturase activity and the ratio of 16∶1/(16∶0+16∶1) fatty acids in liver lipids were inversely related to the proportion of 18∶2 in liver lipid. Plasma insulin concentrations and rates of glucose-stimulated insulin release in vivo were higher in obese rats compared with lean rats, and plasma insulin levels were higher in rats fed S compared with T. There was no relationship between Δ9 desaturase activity and either plasma insulin concentration or rates of insulin release in vitro. These findings suggest that hepatic Δ9 desaturase activity of Zucker rats is responsive to changes in the proportion of 18∶2 in liver lipids but is not affected by changes in insulin secretion.     

Fish oil prevents change in arachidonic acid and cholesterol content in rat caused by dietary cholesterol

Rats were fed diets high in either saturated fat (beef tallow) or α-linolenic acid (linseed oil) or eicosapentaenoic and docosahexaenoic acids (fish oil) with or without 2% cholesterol supplementation. Consumption of linseed oil and fish oil diets for 28 days lowered arachidonic acid content of plasma, liver and heart phospholipids. Addition of 2% cholesterol to diets containing beef tallow or linseed oil lowered 20∶4ω6 levels but failed to reduce 20∶4ω6 levels when fed in combination with fish oil. Feeding ω3 fatty acids lowered plasma cholesterol levels. Addition of 2% cholesterol to the beef tallow or linseed oil diet increased plasma cholesterol concentrations but not when fish oil was fed. Feeding the fish oil diet reduced the cholesterol content of liver, whereas feeding the linseed oil diet did not. Dietary cholesterol supplementation elevated the cholesterol concentration in liver in the order: linseed oil > beef tallow > fish oil (8.6-, 5.5-, 2.6-fold, respectively). Feeding fish oil and cholesterol apparently reduced 20∶4ω6 levels in plasma and tissue lipids. Fish oil accentuates the 20∶4ω6 lowering effect of dietary cholesterol and appears to prevent accumulation of cholesterol in plasma and tissue lipids under a high dietary load of cholesterol.     

l-Carnitine effects on chemical composition of plasma lipoproteins of rabbits fed with normal and high cholesterol diets

l-Carnitine plays an important role in the mitochondrial uptake of long-chain fatty acids in mammals. It has recently been shown that this compound has a marked hypo-cholesterolemic effect when used in conjunction with lipid-rich diets. The aim of this study was to investigate the effects of l-carnitine on the fatty acid composition of plasma lipoproteins in rabbits fed with different diets. Four different groups were investigated: group I (standard diet), group II (standard diet supplemented with l-carnitine at 80 mg/kg), group III (standard diet supplemented with 0.5% cholesterol), and group IV (standard diet supplemented with 0.5% cholesterol plus l-carnitine at 80 mg/kg). The feeding period was 126 d. Total plasma cholesterol was indistinguishable in groups I and II, but increased nearly 40-fold in group III. This increment was reduced by 50% in group IV. Correspondingly, total cholesterol content in lipoprotein fractions [very low density lipoprotein (VLDL), low density lipoprotein (LDL), high density lipoprotein (HDL) separated by agarose gel chromatography was the same for groups I and II, while for animals fed a cholesterol-rich diet (III) total cholesterol in VLDL+LDL increased nearly 100-fold when compared with groups I and II but, again, the increment was reduced by 50% in group IV. In contrast, total cholesterol in HDL increased only fivefold for both groups III and IV when compared with groups I and II, indicating no effects of l-carnitine on this parameter. The reduction of total cholesterol in VLDL+LDL particles in animals fed a cholesterol-rich diet plus l-carnitine was associated with a marked decrease in the ratio of cholesteryl ester to free cholesterol and a dramatic increase in their phospholipid content; opposite effects were observed for HDL. l-Carnitine induced a marked decrease in the saturated to unsaturated C₁₆+C₁₈ fatty acid ratio in cholesteryl esters associated with VLDL and LDL from animals fed with both normal and cholesterol-rich diets. The opposite effect (a large increase in the saturated to unsaturated fatty acid ratio) was observed for both cholesteryl esters and phospholipids associated with HDL in animals fed with both diets. The results suggested that the hypocholesterolemic effects of l-carnitine could be associated with increased systemic breakdown of cholesteryl esters, a probable increase in reverse cholesterol transport, and the stabilization of a phospholipid-based structure of VLDL+LDL particles.     

Dietary fats rich in saturated fatty acids (12∶0, 14∶0, and 16∶0) enhance gallstone formation relative to monounsaturated fat (18∶1) in cholesterol-fed hamsters

To test the possibility that dietary palmitic acid (16∶0) may be lithogenic, different fats were blended to exchange 18∶1 in olive oil with either 16∶0 in palm stearin, 12∶0+14∶0 in coconut oil, or 14∶0+16∶0 in butterfat. Dietary 18∶2 was held constant at 1.2% energy (en) (with extra safflower oil as needed) in these four purified diets containing low fat (11% of total energy) and 0.4% cholesterol. A fifth, high-fat diet provided 40% of the total energy as the 16∶0-rich blend. All hamsters fed the low-fat, 16∶0-rich blend for six weeks developed cholesterol gallstones (8/8). Although the gallstone incidence was lower for the 12∶0+14∶0-rich diet (5/8), the severity of stone formation in affected hamsters was equal to that in the low-fat, 16∶0-rich group. Mucin accumulation in gallbladder bile was often associated with cholesterol gallstones in diets containing 16∶0, but was minimal in 18∶1-rich and 12∶0+14∶0-rich groups. Neither the lithogenic index (all>1.0), plasma lipids, nor liver cholesterol was a selective predictor of stone formation. The high-fat, 16∶0-rich diet actually decreased cholesterol stone incidence (3/8) and severity, but yielded a high incidence of pigment stones (5/8). Thus, saturated fat and 16∶0per se were not responsible for the exaggerated lithogenesis. Because the antilithogenic 18∶1-rich diet also normalized the 18∶2 intake (1.2% en) relative to previous butter diets (0.3% en), the potential importance of essential fatty acids (EFA) deficiency in the model was tested in a second study by feeding graded amounts of 18∶2 (0.3, 0.6, 0.9, and 1.2% en) as safflower oil in four low-fat, butter-rich diets (11% en as fat) without alleviating gallstone incidence or severity. These studies indicate that substitution of 18∶1 for saturated fatty acids in low-fat diets reduces gallstone formation without affecting the lithogenic index. Furthermore, intake of 18∶2 at or below the EFA requirement does not appear to be a major factor in this model.     

Dietary modulation of fatty acid profiles and oxidative status of rat hepatocyte nodules: Effect of different n−6/n−3 fatty acid ratios

Male Fischer rats were fed the AIN76A diet containing varying n−6/n−3 FA ratios using sunflower oil (SFO), soybean oil (SOY), and SFO supplemented with EPA-50 and GLA-80 (GLA) as fat sources. Hepatocyte nodules, induced using diethylnitrosamine followed by 2-acetylaminofluorene/partial hepatoctomy promotion, were harvested, with surrounding and respective dietary control tissues, 3 mon after partial hepatectomy. The altered growth pattern of hepatocyte nodules in rats fed SFO is associated with a distinct lipid pattern entailing an increased concentration of PE, resulting in increased levels of 20∶4n−6. In addition, there is an accumulation of 18∶1n−9 and 18∶2n−6 and a decrease in the end products of the n−3 metabolic pathway in PC, suggesting a dysfunctional Δ-6-desaturase enzyme. The hepatocyte nodules of the SFO-fed rats exhibited a significantly reduced lipid peroxidation level that was associated with an increaser in the glutathione (GSH) concentration. The low n−6/n−3 FA ratio diets significantly decreased 20∶4n−6 in PC and PE phospholipid fractions with a concomitant increase in 20∶5n−3, 22∶5n−3, and 22∶6n−3. The resultant changes in the 20∶4/20∶5 FA ratio and the 20∶3n−6 FA level in the case of the GLA diet suggest a reduction of prostaglandin synthesis of the 2-series. The GLA diet also counteracted the increased level of 20∶4n−6 in PE by equalizing the nodule/surrounding ratio. The low n−6/n−3 ratio diets significantly increased lipid peroxidation levels in hepatocyte nodules, mimicking the level in the surrounding and control tissue while GSH was decreased. An increase in n−3 FA levels and oxidative status resulted in a reduction in the number of glutathione-S-transferase positive foci in the liver of the GLA-fed rats. Modulation of cancer development with low n−6/n−3 ratio diets containing specific dietary FA could be a promising tool in cancer intervention in the liver.     

Differential effects of dietary linoleic and α-linolenic acid on lipid metabolism in rat tissues

Comparative effects of feeding dietary linoleic (safflower oil) and α-linolenic (linseed oil) acids on the cholesterol content and fatty acid composition of plasma, liver, heart and epididymal fat pads of rats were examined. Animals fed hydrogenated beef tallow were used as isocaloric controls. Plasma cholesterol concentration was lower and the cholesterol level in liver increased in animals fed the safflower oil diet. Feeding the linseed oil diet was more effective in lowering plasma cholesterol content and did not result in cholesterol accumulation in the liver. The cholesterol concentration in heart and the epididymal fat pad was not affected by the type of dietary fatty acid fed. Arachidonic acid content of plasma lipids was significantly elevated in animals fed the safflower oil diet and remained unchanged by feeding the linseed oil diet, when compared with the isocaloric control animals fed hydrogenated beef tallow. Arachidonic acid content of liver and heart lipids was lower in animals fed diets containing safflower oil or linseed oil. Replacement of 50% of the safflower oil in the diet with linseed oil increased α-linolenic, docosapentaenoic and docosahexaenoic acids in plasma, liver, heart and epididymal fat pad lipids. These results suggest that dietary 18∶2ω6 shifts cholesterol from plasma to liver pools followed by redistribution of 20∶4ω6 from tissue to plasma pools. This redistribution pattern was not apparent when 18∶3ω3 was included in the diet.     

Influence of diet on the kinetic behavior of hepatic carnitine palmitoyltransferase I toward different acyl CoA esters

The influence of diet on the kinetics of the overt form of rat liver mitochondrial carnitine palmitoyltransferase (CPT I; EC 2.3.1.21) was studied using rats fed either a low-fat diet (3% w/w fat), or diets which were supplemented with either olive oil (OO), safflower oil (SO) or menhaden (fish) oil (MO) to 20% w/w of fat (high fat diets). When animals were fed each of these four diets for 10 days, the order of the apparent maximal activity (V_max) of CPT I toward various individual fatty acyl CoA, when measured under a fixed molar ratio of acyl CoA/albumin, was 16∶1n−7>18∶1n−9>18∶2n−6>16∶0>22∶6n−3, and was thus not affected by the fat composition of the diet. However, in all but one case, the SO and MO diets elicited a higher V_max for each substrate than either the LF diet or the high fat OO diet. The apparent K _0.5 for the different acyl CoA esters was generally lowest in LF-fed animals, and highest in those fed the high-fat SO diet. Moreover, when compared with the situation of animals fed high-fat diets, the K _0.5 values of CPT I in LF-fed animals for palmitoyl CoA and oleoyl CoA were low. This possession by CPT I of a high “affinity” toward these nonessential fatty acyl CoAs, but a lower “affinity” toward linoleoyl CoA, the ester of an essential fatty acid, may enable this latter fatty acid to be spared from oxidation when its concentration in the diet is low. The data also emphasize that palmitoleoyl CoA, if available in the diet, is likely to be utilized by CPT I at a high rate.     

Plasma lipids and fatty acids in urbanized Bushmen,Hereros and Kavangos of Southern Africa (Namibia)

Thirty-nine urbanized ethnic Namibian people comprising 21 Bushmen (semi-urbanized), 7 Hereros and 11 Kavangos were assessed for plasma lipids and fatty acid (FA) composition. Total cholesterol and triacylglycerol concentrations were measured by enzymatic methods, and neutral lipid FA composition by gas-liquid chromatography. The results demonstrated that while total cholesterol concentrations were not significantly different, significant differences in triacylglycerol concentrations (P<0.05) were seen between Bushmen and Kavangos. By comparing Bushmen with Hereros and Kavangos, significant differences between Bushmen and Kavangos were also observed in plasma triacylglycerol FA compositions, particularly 16∶0 (32.73%vs. 25.05%), 16∶1n−7 (7.00%vs. 5.06%), 18∶2n−6 (9.30%vs. 22.25%) and 20∶3n−6 (0.12%vs. 0.48%), while Kavangos had higher 20∶4n−6 levels than Hereros (1.44%vs. 2.00%). In plasma cholesteryl esters, Bushmen were significantly different from Kavangos in 16∶1n−7 (8.85%vs. 4.93%), 18∶1n−9 (32.06%vs. 23.07%) and 20∶4n−6 (6.91%vs. 10.00%). Significant differences were also observed between Bushmen and Hereros in 18∶0 (1.08%vs. 1.29%) and 18∶2n−6 (35.68%vs. 45.50%). The FA of Namibian groups were also compared with South African reference groups comprising urbanized whites and Xhosas and rural Vendas. The differences in blood lipid values can be explained primarily by excessive alcohol consumption. These results suggest that semi-urbanized Bushmen have changed their diets under urbanized conditions which may increase their risk of coronary heart disease.