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PubMed1985

Statistical errors invalidate conclusions in "Caffeine and unsaturated fat diet significantly promotes DMBA-induced breast cancer in rats".

The conclusion drawn in a recent paper by Minton and associates (Cancer 1983; 51:1249-1253), that caffeine and an unsaturated fat diet significantly promoted dimethylbenz(a)anthracene (DMBA)-induced breast cancer in rats, is based on fallacious statistical reasoning. Minton and associates based their conclusion on the mean latency to first tumor appearance for rats diagnosed with tumors. However, evaluation of percentages of tumor-bearing rats yields contrary results. Using data from a totally negative hypothetical two-group experiment, we demonstrate how such "conflicting" results could arise from differential intercurrent mortality in the two groups. The correct statistical analysis of this hypothetical experiment allows for differential intercurrent mortality and no conflict arises; the data of Minton and associates need to be analyzed by these methods.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1995

Renal hemodynamic and histological consequences of diets high in unsaturated fat, protein or sucrose in obese Zucker rats.

The objective of this study was to determine the long-term effect of different dietary macronutrients on renal hemodynamics in obese Zucker rats. Female obese (fa/fa) Zucker rats were allowed to eat control chow (ObCL) or diets high in unsaturated fat (ObHF), protein (ObHP) or sucrose (ObHS) for a period of 24 weeks. Lean chow fed (LnCL) Zucker rats served as lean controls. After 24 weeks of dietary treatments, glomerular filtration rate (GFR, ml/mg/g, mean +/- SE) of ObHP and ObHS (0.38 +/- 0.06 and 0.27 +/- 0.05) rats were significantly (p < 0.005) lower than ObCL (0.74 +/- 0.05) and ObHF (0.88 +/- 0.1) rats. In a similar manner, the effective renal plasma flow (ERPF, ml/min/g) was significantly (p < 0.005) lower in ObHP and ObHS (1.28 +/- 0.16 and 1.04 +/- 0.2) than ObCL (2.46 +/- 0.31) or ObHF (2.85 +/- 0.25) rats. The ObHF rats appeared "protected" since they had similr GFR and ERPF but less proteinuria and glucosuria than ObCL rats. Histological examination of renal tissue from ObHP and ObHS fed rats revealed significant (p < 0.005) increase in sclerosis relative to ObCL rats. The sclerosis of renal tissue in ObHF was minimized and was found to be similar to ObCL rats. The mean arterial pressure and heart rates were similar in all dietary treated obese Zucker rats. When comparing obese and lean controls, ObCL rats had significantly (p < 0.03) lower GFR (0.74 +/- 0.05 vs 0.92 +/- 0.05) but similar ERPF (2.46 +/- 0.3 vs 2.82 +/- 0.12) than LnCL rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1978

Effects of saturated and unsaturated fats given with and without dietary cholesterol on hepatic cholesterol synthesis and hepatic lipid metabolism.

Hepatic cholesterol synthesis was studied in rats after consuming diets of varying neutral lipid and cholesterol content. Cholesterol synthesis was evaluated by measuring 3-hydroxy-3-methylglutaryl-CoA reductase and by determining the rate of 3H-labeled sterol production from [3H]mevalonate. Results were correlated with sterol balance data and hepatic lipid content. Hepatic cholesterol synthesis was relatively great when cholesterol was excluded from the diet. The source of neutral dietary lipids, saturated vs. unsaturated, produced no change in hepatic sterol synthesis. Values for fecal sterol outputs and hepatic cholesterol levels were also similar in rats consuming either saturated or unsaturated fats. When 1% cholesterol was added to the diet, hepatic cholesterol synthesis was suppressed but the degree of suppression was greater in rats consuming unsaturated vs. saturated fats. This was associated with greater accumulation of cholesterol in livers from rats consuming unsaturates and a reduction in fecal neutral sterol output in this group as opposed to results from rats on saturated fats. Cholesterol consumption also altered the fatty acid composition of hepatic phospholipids producing decreases in the percentages of essential polyunsaturated fatty acids. It is concluded that dietary cholesterol alters cholesterol and fatty acid metabolism in the liver and that this effect is enhanced by dietary unsaturated fats.

Animals↗
PubMed1992

An unsaturated fat diet prevents the increased angiotensin II vascular responses in renal artery stenosis.

OBJECTIVE: The aim was to characterise angiotensin II constrictor responses in two kidney, one clip (2K1C) renal hypertensive rats fed a diet with a high unsaturated fatty acid content. METHODS: Two diets with the same total fat (37% by energy; 17% by weight) but different unsaturated fat contents were fed to rats for a three month period. Thirty four Sprague Dawley rats were used per diet group. After one month on the diets, a group of 19 rats in each diet group was operated upon to induce 2K1C hypertension. A separate group of 15 rats within each diet group received sham operations. Systolic blood pressure was measured weekly from prior to surgery to the end of the three month feeding period. At three months, angiotensin II constrictor responses were evaluated in the isolated kidney vascular preparation and in intact anaesthetised rats fed the different diets. Phenylephrine constrictor responses were also evaluated in intact anaesthetised rats in order to exclude structural vascular changes accounting for differences in angiotensin II constrictor responses. RESULTS: The diet high in unsaturated fats prevented the development of hypertension in 2K1C rats [systolic pressure 134(7) mm Hg at eight weeks] compared to their own preoperative blood pressures [124(3) mm Hg], and to the 2K1C rats fed the control diet [163(7) mm Hg at eight weeks]. The diet high in unsaturated fats did not alter blood pressures in sham operated rats. In isolated perfused kidneys and in anaesthetised 2K1C rats fed the control diet, angiotensin II caused a greater vascular response compared to the sham operated groups. The unsaturated fat diet prevented this effect. No differences were found in blood pressure responses to phenylephrine. CONCLUSIONS: These data suggest that the antihypertensive effect of a high unsaturated fat diet may in part be due to a depressed responsiveness of vascular smooth muscle to endogenous angiotensin II. The effect is likely to be due to modulation of angiotensin II vascular responses by local vascular changes that cannot be accounted for by structural vascular differences.

Angiotensin II↗
PubMed1985

Dietary fat unsaturation enhances drug metabolism in cebus but not in squirrel monkeys.

Antipyrine disappearance and sleeping time following barbiturate anesthesia were assessed to evaluate the effects of dietary corn oil and coconut oil on the drug-metabolizing enzyme systems (DMES) in cebus (Cebus albifrons) and squirrel (Saimiri sciureus) monkeys. Plasma antipyrine clearance (half-life) was measured in both species before and after induction of DMES by i.v. injection of barbiturates on two consecutive days. Sleeping time was measured after administration of either pentobarbital or hexobarbital and proved to be the most demonstrable measure of diet-drug interaction. In neither cebus nor squirrel monkeys was antipyrine half-life significantly affected by dietary fat. Sleeping time for the coconut oil-fed squirrel monkeys was shorter than for those fed corn oil, whereas corn oil-fed cebus awoke sooner than the coconut oil-fed cebus. Thus, barbiturate but not antipyrine metabolism in monkeys can be influenced by dietary fat unsaturation, and the effect appears to be species dependent. Genetic differences in phospholipid metabolism are thought to underlie this difference.

Animals↗
PubMed2006

Age-related mitochondrial DNA deletion in rat liver depends on dietary fat unsaturation.

We fed male Wistar rats lifelong on virgin olive (rich in the monounsaturated oleic acid) or sunflower (rich in the polyunsaturated linoleic acid) oil-based diets. At 6 and 24 months, liver mitochondria were analyzed for a mitochondrial DNA (mtDNA) deletion, reactive oxygen species, antioxidants, and ultrastructural alterations. An aging-related increase in the relative amount of the deletion was observed for both dietary groups, being higher in animals fed sunflower oil. Oxidative stress was lower in virgin olive oil-fed animals. Aging led to higher superoxide dismutase, catalase, and glutathione peroxidase activities and increased alpha-tocopherol and coenzyme Q. Mitochondria from aged animals fed sunflower oil exhibited a lower number of cristae and a higher circularity. Results suggest that the age-related increase of the relative amount of deleted mtDNA depends on fat unsaturation. Moreover, the studied mtDNA deletion was correlated with mitochondrial oxidative stress and ultrastructural alterations.

Aging↗
PubMed1966

Composition of lipids in human serum and adipose tissue during prolonged feeding of a diet high in unsaturated fat.

Elderly institutionalized men were assigned at random to two groups, one of which received a conventional diet while the other was fed a diet in which the major modification was substitution of unsaturated for saturated fat. Changes in serum lipids and in adipose tissue over periods up to 5 years are described. In control subjects, mean serum cholesterol rose 4% over the first 20 months, then fell during the next 40 months to a level 10% below the starting concentration. In the experimental group there was an immediate drop, followed by further changes roughly parallel to those in the control subjects. The mean difference between the control and experimental groups was 14.0% of the starting level. Changes in serum total lipid were similar, but the percentage difference between control and experimental groups was only 6.8% of the baseline level. All major esterified serum lipid fractions of experimental subjects contained increased concentrations of linoleic acid. This was most marked in triglyceride, which at 3 years had a composition similar to that of the dietary fat in both groups of subjects. Adipose tissue linoleic acid rose in men on the experimental diet from 11% of total fatty acid at time zero to 32% at 5 years. The rise could be fitted to an exponential function with a half-time of 680 days. The rate of rise during the 1st year was correlated negatively with initial body weight and positively with weight gain; the influence of adherence to the diet was much less pronounced.

Adipose Tissue↗
PubMed2000

Effects of saturated and unsaturated fats with vitamin E supplementation on the antioxidant status of broiler chicken tissues.

The influence of fish oil (highly unsaturated) and beef tallow (highly saturated) with vitamin E (100 IU/kg) supplementation on the antioxidant status of broiler chicken cockerels was investigated. Chicks were fed a control diet with no added fat, 40 g/kg each of fish oil and beef tallow diets, respectively, from 11 to 42 days of age. Tocopherol concentration and the rate of lipid peroxidation, thiobarbituric acid reactive substance (TBARS) in liver, fatty acid composition of the liver lipids, blood serum total antioxidant status (TAS), and reduced glutathione (GSH) content were determined. Vitamin E supplementation of the diet increased liver alpha-tocopherol content in chicks regardless of the type of dietary fat. Fish oil diet resulted in higher liver TBARS value while beef tallow diet showed lower values compared to the control diet. Vitamin E supplementation reduced liver TBARS as well as serum GSH, and raised serum TAS for all diets. Serum GSH was the same for vitamin E supplemented diets regardless of the fat supplement. Fish oil diets resulted in a significant increase in hepatic lipid n-3 PUFA content. A significant positive correlation was found between liver TBARS and n-3 PUFA content. No relationships were established, however, between liver TBARS and n-6 PUFA or saturated fatty acids. The results suggest that feeding oils rich in n-3 PUFA increases tissue concentration of these fatty acids, consequently increasing tissue lipid peroxidation and reducing the antioxidative status of broiler chickens. Supplementing high levels of vitamin E with such oils may increase tissue oxidative stability. Serum TAS or GSH may be used as a measure of antioxidative status in chickens.

Animal Feed↗
PubMed1988

Effects of low fat diets differing in degree of fat unsaturation on plasma lipids, lipoproteins, and apolipoproteins in adult men.

The effects of two low fat diets with differing ratios of polyunsaturated to saturated fatty acids (P/S) on blood lipids, lipoproteins (LP), and apolipoproteins (Apo) were studied in 23 adult men, 30-60 years old, using a crossover design. Both test diets had 25% fat calories with either a P/S of 0.3 (Diet 1) or a P/S of 1.0 (Diet 2) and equivalent amounts of cholesterol. The study consisted of four periods: a 5-week prestudy on self-selected diet (SS), two 6-week test diet periods followed by a second 5-week post-study period on the SS diet. When compared with the SS diet, Diet 2 lowered the mean plasma total cholesterol (TC) by about 20% (P less than 0.01). Low density lipoprotein (LDL) cholesterol was also decreased by about 18% by Diet 2 (P less than 0.01). The high P/S diet did not cause a change in total cholesterol in the high density lipoprotein (HDL) subclass2 (HDL2) when compared to the SS diet. Levels of triglycerides (TG) were slightly reduced in HDL2 but showed a greater reduction in HDL3 in both diets. Phospholipids (PL) were significantly reduced in HDL2 and in HDL3, but the reduction in HDL3 PL was not statistically significant. Apo A-I levels were not changed by either diet when compared with the SS diet, but Apo A-II levels of HDL2 and HDL3 were significantly decreased by the low fat diets, and there was no P/S effect. No other consistent changes in apoprotein levels occurred. Our data suggest that, in men with normal lipid levels, practical dietary changes involving a moderate increase in P/S from 0.3 to 1.0 in a low fat, low cholesterol diet do influence lipoprotein composition and apoprotein distribution in a short time. The reduction in cholesterol in total lipid composition and in LDL lipids which accompanied the reduction of dietary fat and cholesterol are considered to be beneficial.

Adult↗
PubMed1996

Lactational responses of dairy cows fed unsaturated fat from extruded soybeans or sunflower seeds.

Nine multiparous Holstein cows were used in a replicated 3 x 3 Latin square to evaluate the response to diets containing equal amounts of supplemental fat from extruded soybeans or sunflower seeds. Both fat sources contained about 66% polyunsaturated fatty acids; for soybeans, about 8% was linolenic acid, but sunflower seeds contained mostly linoleic acid. Periods were 5 wk, and data were collected the last 3 wk of each period. Total mixed diets were (DM basis) 25% corn silage, 25% alfalfa hay, and 50% concentrate mix. Control concentrate mix contained primarily corn, barley, and soybean meal; extruded soybeans or rolled sunflower seeds replaced portions of the corn, barley, and soybean meal in isonitrogenous (17% CP) diets. Milk yield was higher for cows fed supplemental fat. Percentages of milk fat and protein and DMI were similar for all three dietary treatments. Milk fat from cows fed soybeans or sunflower seeds contained higher concentrations of unsaturated fatty acids and long-chain fatty acids than did milk fat from cows fed the control diet. Milk yield and composition were similar for cows fed soybeans, or sunflower seeds. Soybeans or sunflower seeds can be used as dietary fat supplements to increase milk yield and the proportion of unsaturated fatty acids in milk fat.

Animal Feed↗
PubMed1988

The influence of dietary low and high unsaturated fats and cholesterol on the fatty acid pattern of serum and aortic cholesteryl esters and the lipid deposits of pig aorta.

16 three-month-old female pigs were divided into 3 groups. 6 animals received a semi-synthetic diet containing 15% sunflower oil (g/100 g food) and 1.25% cholesterol (SF group). In 6 animals the sunflower oil was replaced by beef tallow (BT group). 4 control animals 1.5% sunflower oil and without cholesterol. The serum cholesterol levels of the SF group rose moderately, those of the BT group moderately or highly. The relative lipid infiltrated intima area (LIA) and the cholesteryl ester (CE) content of aortas were generally lower in the SF group than in the BT group in comparison to the serum cholesterol levels. The dietary fatty acid pattern determined the fatty acid composition of CE in the serum and extracellular lipid of the aortic lesions. With regard to the intracellular changes of fatty acid pattern of CE (decrease in dienoic acid, predominantly linoleic acid, and increase in monoenoic acids, predominantly oleic acid, and in trienoic acids and higher unsaturated fatty acids), there were important differences between the 2 dietary groups. The dienoic acid content of CE decreased intracellularly from 61% to 30.5%, at the most, in the SF group, and then stopped. In the BT group only 26-35% dienoic acid was available from the extracellular CE and was reduced intracellularly to 9% at the most. In the SF group the intracellular increase in monoenoic acid content of CE was related to the decrease in dienoic acid content. In the BT group this was true only for some lipid deposits of the aorta; in other lesions the monoenoic acid content remained nearly constant or even decreased with decrease in linoleic acid whereas the increase in trienoic acid content was especially high suggesting that an unphysiological trienoic acid (20:3 delta 5, 8, 11), originating from oleic acid, was formed in greater amounts. Our findings point to the development of an essential fatty acid deficiency in the foam cells of aortic lesions in the BT group which may result in an unfavorable influence on the cholesterol clearance from the cells and the arterial wall.

Animals↗
PubMed1998

The influence of dietary saturated and unsaturated fat on hepatic cholesterol metabolism and the biliary excretion of chylomicron cholesterol in the rat.

The biliary excretion of [3H] cholesterol carried in chylomicrons derived from palm oil (rich in long chain saturated fatty acids), olive oil (rich in monounsaturated fatty acids) or corn oil (rich in n-6 polyunsaturated fatty acids was studied in vivo in rats fed the corresponding oil in the diet for 21 days. The secretion of radioactivity into bile as both bile acids and unesterified cholesterol was significantly slower in the animals fed palm oil as compared to those given olive or corn oil, indicating that dietary saturated fat retards the excretion of cholesterol from the diet as compared to mono- or n-6 polyunsaturated fat. In order to investigate the mechanisms underlying these differences, the influence of the three high fat diets on cholesterol esterification, cholesteryl ester hydrolysis and bile acid synthesis in the liver and on biliary lipid output were also measured. The ratio of cholesterol esterification to cholesteryl ester hydrolysis was markedly raised in the olive and corn oil-fed as compared to palm oil-fed animals. Biliary cholesterol secretion was higher in corn oil-fed rats than in those fed olive or palm oil or a low fat diet, and this was associated with a markedly increased lithogenic index in these animals. The activity of cholesterol 7alpha hydroxylase was higher in the olive and corn oil-fed than in the palm oil-fed animals, although the expression of mRNA for the enzyme was increased only in the olive oil diet group. After 20 h biliary drainage, the rate of bile acid secretion into bile was increased in the rats fed olive and corn oil rather than to palm oil. These findings indicate that feeding rats mono- or n-6 polyunsaturated as compared to saturated fat in the diet promotes the storage of cholesteryl ester in the liver and leads to increased bile acid synthesis, resulting in the more rapid excretion of cholesterol originating from the diet via the bile.

Animals↗
PubMed1983

Influence of trans unsaturated fats on experimental atherosclerosis in rabbits.

To test the effects of trans unsaturated fatty acids (t-FA) on atherosclerosis, lipidemia and enzyme activities, rabbits were fed a semipurified, cholesterol-free diet containing 40% sucrose, 25% casein and 14% fat for 5 months. Two experimental diets provided either 6% (high) or 3.2% (low) t-FA. The control group was fed a fat of composition similar to the two experimental diets but free of t-FA. Serum cholesterol and triglycerides were elevated in the rabbits fed 6% t-FA. Liver glycerides were also elevated in this group. The fatty acids of plasma, erythrocytes, epididymal fat, liver microsomes and liver mitochondria reflected the dietary composition. Levels of aortic atherosclerosis were identical in the three groups. There were no significant differences in activity of five hepatic enzymes: glucose-6-phosphatase (microsomal), fatty acid synthetase (cytosolic), malate dehydrogenase, beta-hydroxybutyrate dehydrogenase and monoamine oxidase (mitochondrial).

Adipose Tissue↗
PubMed1987

In vivo regulation of hepatic LDL receptor mRNA in the baboon. Differential effects of saturated and unsaturated fat.

The effects of diets enriched with cholesterol and different fats upon plasma lipoproteins and hepatic low density lipoprotein (LDL) receptor mRNA levels were studied in a group of 18 normal baboons. Animals were fed diets containing 1% cholesterol and 25% fat as either coconut oil, peanut oil, or olive oil for a period of 20 weeks. Plasma total cholesterol, high density lipoprotein (HDL) cholesterol, beta-lipoprotein (LDL + very low density lipoprotein) cholesterol, apolipoprotein B and apolipoprotein A-I were measured in samples obtained at 4-week intervals. All three diet groups demonstrated a statistically significant increase in plasma cholesterol as compared to base line throughout the experiment. Hepatic LDL receptor (LDL-R) mRNA levels were quantified by dot blot hybridization in serial liver biopsies. Animals fed saturated fat sustained a significant reduction in hepatic LDL-R mRNA as compared to those fed either monounsaturated or polyunsaturated fat. A strong negative correlation between LDL-R mRNA and plasma total cholesterol (r = -0.71), HDL cholesterol (r = -0.76), and plasma apo A-I (r = -0.77) was observed only in those animals fed coconut oil. Weak negative correlations between LDL-R mRNA and other plasma parameters did not achieve statistical significance. We conclude that saturated and unsaturated oils may influence plasma cholesterol levels in part through differential effects on LDL receptor biosynthesis in baboons.

Animals↗
PubMed1996

Cholesterol and unsaturated fat diets influence lipid and glucose concentrations in rats.

The present study investigated the effects of dietary cholesterol and monounsaturated and polyunsaturated fatty acids on plasma lipids and glucose concentrations. Four groups of ten male Wistar albino rats were fed diets of different fatty acid composition for 40 days. The control group consumed nonpurified diet (containing fat 3.7 g/100 g diet), and cholesterol, olive oil, and safflower oil groups consumed the nonpurified diet enriched with 14 g fat/100 g diet with egg yolk, olive oil, or safflower oil, respectively. Compared with the control, the diet enriched with cholesterol significantly increased fasting plasma cholesterol (P < 0.01), triacylglycerol (P < 0.01), total lipid (P < 0.01) and glucose (P < 0.05) concentrations; in the olive oil group, cholesterol and triacylglycerol levels were significantly increased compared with control group (P < 0.01 in both instances). In safflower oil group, triacylglycerol levels were also significantly increased (P < 0.05) compared with the controls. After comparing diets providing the same amount of fat (cholesterol, olive oil, and safflower oil groups), higher cholesterol, triacylglycerol and total lipid levels were observed in the cholesterol group than in the olive oil group (P < 0.01, P < 0.05 and P < 0.01, respectively), and safflower oil group (P < 0.01 in all instances). High-density lipoprotein-cholesterol concentrations were significantly lower in the cholesterol group than in the olive oil and safflower oil groups (P < 0.05 in both instances) and fasting plasma glucose levels were higher in the cholesterol than in the olive oil (P < 0.05) and safflower oil groups (P < 0.01). Finally, after comparing lipid and glucose levels in the unsaturated fatty acids-enriched diets, higher plasma cholesterol concentrations were observed in the olive oil than in the safflower oil group (P < 0.05). These data suggest that not only the amount but also the type of dietary fat can influence serum lipid levels.

Animals↗