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Trans fatty acids and coronary heart disease risk. Report of the expert panel on trans fatty acids and coronary heart disease.

This review critically evaluates the scientific data on trans fatty acids and coronary heart disease (CHD) risk. Trans fatty acids are present in a variety of foods but they contribute only 4-12% of total dietary fat intake (2-4% of total energy intake) in the United States. The physical properties of trans fatty acids are intermediate between cis and saturated fatty acids, but a trans double bond is chemically less reactive than a cis double bond. Biochemical data indicate that trans fatty acids are subject to the same metabolic control mechanisms that regulate the metabolism of saturated and cis-isomeric fatty acids. Equivocal results have been reported in observational studies of trans fatty acid intake and CHD because of numerous methodologic limitations, including the difficulties inherent in quantifying trans fatty acid intake. Studies in hamsters indicate that trans fatty acids have a neutral effect on low-density-lipoprotein (LDL)-receptor activity, LDL-cholesterol production rate, and plasma LDL-cholesterol concentration. Other animal studies show no differences in atherosclerosis incidence or severity between diets containing hydrogenated and native vegetable oils. In clinical studies partially hydrogenated oils lower total and LDL-cholesterol concentrations when substituted for animal or vegetable fats rich in saturates but raise total and LDL-cholesterol concentrations when substituted for the unhydrogenated native oil. The effects of trans fatty acids on high-density lipoprotein cholesterol and lipoprotein(a) concentrations are unclear because of limited and conflicting clinical data. Data supporting a relation between trans fatty acid intake and CHD risk are equivocal compared with extensive data from studies in animals and humans linking saturated fat intake to CHD. Additional research is needed to resolve questions about the independent effects of trans fatty acids on plasma lipoproteins and their mechanisms of action.

Animals↗

Influence of intestinal resection, type of dietary fat and time on the digestive and metabolic utilization of fat in rats.

The influence of diets containing different types of fat (olive oil or a mixture of 1/3 medium chain triglycerides, 1/3 sunflower seed oil and 1/3 olive oil), and the effect of ursodeoxycholic acid, an exogenous bile acid, on the digestive and metabolic utilization of fat and on the relative percentages of fatty acids in serum in adult rats with 50% distal small intestinal resection and in sham-operated controls three months after surgery has been studied. In resected rats given olive oil as the dietary source of fat, the digestive utilization of fat decreased with respect to controls. Substitution of 1/3 medium chain triglycerides and 1/3 sunflower seed oil for 2/3 of the dietary fat source improved the digestive utilization of fat as judged from the apparent digestibility coefficient, and this improvement was maintained when ursodeoxycholic acid was added to the diet. With both sources of dietary fat tested, intestinal resection led to a decrease in serum levels of triglycerides and cholesterol. However, no significant differences were observed between resected animals fed either type of diet and controls with respect to the relative percentages of fatty acids in serum, saturated and insaturated fatty acid indices or omega 3/omega 6 ratio. The fatty acid profile in serum revealed no deficit in essential fatty acids caused by intestinal resection, type of diet or time, but did reflect clearly the source of dietary fat.

Animals↗

SNPs in the porcine PPARGC1a gene: interbreed differences and their phenotypic effects.

Due to its function, the peroxisome proliferative activated receptor-gamma, coactivator-1alpha (PPARGC1A) gene is a candidate in the search for genes that may affect production traits in the pig. The purpose of this study was to screen for new SNPs in exon 8 of the porcine PPARGC1A gene and to test their possible association with production traits. Altogether 736 pigs representing five breeds Polish Landrace, n=242; Polish Large White, n=192; Hampshire, n=27; Duroc, 21; Pietrain, n=12) and synthetic line 990 (n=242) were scanned via SSCP assay. Four SNPs were found; two new ones: C/G (His338Gln) and G/A Thr359Thr), and two previously reported ones: C/A (Arg369Arg) and T/A Cys430Ser). The missense T/A and C/G SNPs demonstrated pronounced interbreed variability in terms of allele frequencies, including the exclusive presence of the C/G substitution in the Hampshire breed. The tested SNPs occurred in five putative haplotypes, and their frequency also differed substantially between breeds. The association of the SNPs with production traits was tested for G/A (Thr359Thr), C/A (Arg369Arg) and T/A (Cys430Ser) substitutions in Polish Large White, Polish Landrace and line 990. The analysis revealed only breed-specific associations. The T/A (Cys430Ser) SNP was related to the feed conversion ratio in the Polish Large White (P=0.02), and the silent G/A and C/A substitutions were respectively associated with abdominal fat in line 990 and backfat thickness in Polish Landrace (P=0.04). The combined effects of the substitutions were estimated as haplotype effects. Three significant contrasts between haplotypes were calculated, but the observed associations were again only breed-specific.

Animals↗

Effect of added dietary fat on performance, rumen characteristics, and plasma metabolites of midlactation dairy cows.

Effects of supplemental Jet-Sploded canola seed in the diets of dairy cows on milk yield and composition and blood metabolite concentrations were investigated. Twenty multiparous and 5 primiparous midlactation Holstein cows were assigned to treatments following a 3-wk covariate period; cows were then on the treatments for 70 d. Ten of the cows had previously been fitted with rumen cannulas. Five concentrate mixtures containing 0, 7.5, 15, 22, or 29% Jet-Sploded canola seed (Simons Feed Co., Quimby, IA) (equivalent to 0, 2.66, 5.33, 7.81, and 10.30% added fat, respectively) were formulated by substituting Jet-Sploded canola seed for barley and canola meal. Diets consisted of 25% alfalfa silage, 25% whole-crop oat silage, and 50% of one of the concentrate mixtures (dry matter basis). An increase in the amount of dietary fat from Jet-Sploded canola seed did not influence feed intake, milk yield or composition, or milk component yields. The inclusion of Jet-Sploded canola seed in the diet increased long-chain fatty acids and inhibited de novo synthesis of medium-chain fatty acids in milk. Mean total volatile fatty acids in the rumen and propionate concentration were reduced in a linear fashion by treatment. The inclusion of Jet-Sploded canola seed in the diets of mid-lactation cows altered rumen and blood metabolite concentrations; however, these changes had minimal effects on yield responses with the exception of milk fatty acid composition and milk protein content.

Animals↗

Determination of 2,3,7,8-chlorine-substituted dibenzo-p-dioxins and -furans at the part per trillion level in United States beef fat using high-resolution gas chromatography/high-resolution mass spectrometry.

As part of the U.S. EPA Dioxin Reassessment Program, the 2,3,7,8-chlorine-substituted dibenzo-p-dioxins and furans were measured at part per trillion (ppt) levels in beef fat collected from slaughter facilities in the United States. This is the first statistically designed national survey of these compounds in the U.S. beef supply. Analyte concentrations were determined by high-resolution gas chromatography/high-resolution mass spectrometry, using isotope dilution methodology. Method limits of detection on a whole weight basis were 0.05 ppt for TCDD and 0.10 ppt for TCDF, 0.50 ppt for the pentas (PeCDDs/PeCDFs)/hexas (HxCDDs/HxCDFs)/heptas (HpCDDs/HpCDFs), and 3.00 ppt for the octas (OCDD/OCDF). Method detection and quantitation limits were established on the basis of demonstrated performance criteria utilizing fortified samples rather than by conventional signal-to-noise or variability of response methods. The background subtraction procedures developed for this study minimized the likelihood of false positives and increased the confidence associated with reported values near the detection limits. Mean and median values for each of the 2,3,7,8-Cl-substituted dioxins and furans are reported, along with the supporting information required for their interpretation. The mean toxic equivalence values for the samples are 0.35 ppt (nondetects = 0) and 0.89 ppt (nondetects = 1/2 LOD).

Animals↗

Dietary monounsaturated and polyunsaturated fatty acids are comparable in their effects on hepatic apolipoprotein mRNA abundance and liver lipid concentrations when substituted for saturated fatty acids in cynomolgus monkeys.

Although studies have shown that saturated and polyunsaturated fats can mediate plasma lipid and apolipoprotein (apo) concentrations at the mRNA level, there is little data on the role of monounsaturated fats. We determined hepatic lipid and apo mRNA levels in 10 cynomolgus monkeys fed three diets that provided 30% of energy as fat with 0.1% cholesterol by weight and differed solely by the substitution of saturated, mono- and polyunsaturated fats as 60% of total fat energy. Total, LDL, and HDL cholesterol, as well as LDL apo B, HDL apo A-I and HDL total apo C concentrations, were reduced with the mono- and polyunsaturated fat diets relative to the saturated fat diet. Although fat saturation did not significantly affect hepatic apo A-I, B, C-II, or E mRNA abundance, hepatic apo C-III mRNA concentrations were uniformly lower (-23%, P < 0.01) with the mono- and polyunsaturated fat diets than with the saturated fat diet. Interestingly, liver triglycerides were significantly elevated with the monounsaturated fat diet relative to the saturated fat diet, but no other differences in hepatic lipids were noted among diets. Hepatic triglyceride composition was shown to reflect dietary fatty acid composition, with liver triglycerides enriched in myristic and palmitic fatty acids during the saturated fat diet, oleic acid during the monounsaturated fat diet and linoleic acid during the polyunsaturated fat diet. We conclude that dietary monounsaturated fats are comparable to polyunsaturated fats in their effects on hepatic lipid and apo mRNA levels in this species, with both unsaturated fats significantly reducing only hepatic apo C-III mRNA abundance relative to saturated fat.

Animals↗

A diet enriched in monounsaturated fats decreases low density lipoprotein concentrations in cynomolgus monkeys by a different mechanism than does a diet enriched in polyunsaturated fats.

To determine the mechanisms whereby dietary fat saturation influences LDL cholesterol and apolipoprotein B concentrations, 10 cynomolgus monkeys were fed each of three experimental diets enriched in saturated, monounsaturated or polyunsaturated fatty acids in a crossover design consisting of three 13-wk periods. Each diet contained 30% of energy as fat with 0.05 mg cholesterol/kJ and differed solely by the isocaloric substitution of fatty acids as 60% of total fat energy. The replacement of dietary saturated fatty acids with either mono- or polyunsaturated fatty acids resulted in significant reductions of plasma total cholesterol (-17% and -30%, respectively), HDL cholesterol (-32% and -41%, respectively), apoA-1 (-37% and -44%, respectively), and apolipoprotein B (-28% and -36%, respectively) concentrations. Additionally, when dietary polyunsaturated fatty acids were substituted for saturated fatty acids, a 27% reduction in VLDL + LDL cholesterol was significant. Metabolic experiments suggested that the significantly reduced concentrations of apolipoprotein B observed during the monounsaturated and polyunsaturated fatty acid phases relative to the saturated fatty acid phase could not be entirely explained by changes in LDL apolipoprotein B clearance but rather were likely due to decreased LDL apolipoprotein B production rates. However, enhanced LDL apolipoprotein B catabolism accounted for the even greater reductions in VLDL + LDL cholesterol and apolipoprotein B concentrations observed during the polyunsaturated fatty acid phase vs. the monounsaturated fatty acid phase. Our data suggest that monounsaturated and polyunsaturated fatty acids lower apolipoprotein B concentrations by distinct mechanisms, with polyunsaturated fatty acids affecting LDL apolipoprotein B catabolism as well as production.

Analysis of Variance↗

A-beta-lipoproteinemia: clinical and laboratory features, therapeutic manipulations, and follow-up study of three members of a Greek family.

We describe the clinicoepidemiologic features, natural history, and therapeutic manipulations in three Greek patients with A-beta-lipoproteinemia (two brothers aged 15 and 29 years, respectively, and one sister aged 30 years). Diarrhea started in infancy in the two brothers and from the age of 13 in the sister. During the second decade of life, central nervous system symptoms became prominent, with fatigue and disturbance in gait and balance. Night blindness developed at a later phase of the disease in the brothers, whereas cavus developed in both legs in the sister. Apolipoprotein B was absent in all patients, and each had more than 50% of acanthocytes present on peripheral smear. The diagnosis of A-beta-lipoproteinemia was established on the basis of small bowel histology and serum lipid estimations. Family studies revealed normal lipid profiles in all healthy members. The human leukocyte antigen (HLA) pattern in the two most severely affected patients was identical. The only detectable difference between the severely ill patients and other members of the family, however, was homozygosity for the HLA B18 antigen, whereas the third patient had no alleles for the HLA B18 antigen. Treatment consisted of a low-fat diet and high doses of vitamins A and E. A modified diet substituting medium-chain triglycerides for dietary fat was also given, with significant improvement in the nutritional status of patients but not in symptoms related to advanced disease, such as retinal and cardiac manifestations. We conclude that the course of the disease in untreated patients is characterized by continuous symptoms. Some of the symptoms, however, especially those related to malabsorption, as well as some anthropometric parameters can be improved by the application of a modified diet including medium-chain triglycerides. We suggest the routine measurement of plasma lipids and apoproteins not only in children with failure to thrive, with unexplained malabsorption, or with neurologic symptoms, but also in adults with chronic diarrhea accompanied by neurologic symptoms or clinical and laboratory signs of malabsorption.

Abetalipoproteinemia↗

Do high carbohydrate diets prevent the development or attenuate the manifestations (or both) of syndrome X? A viewpoint strongly against.

Syndrome X refers to a cluster of abnormalities, associated with resistance to insulin-mediated glucose uptake that increase risk of coronary heart disease. Increases in carbohydrate intake (with reciprocal decreases in fat content) within the boundaries of menus that can be followed in the free-living state have not been shown to decrease insulin resistance, either directly by enhancing insulin sensitivity or indirectly by producing and maintaining weight loss. However, such diets accentuate the metabolic abnormalities that constitute syndrome X. Because substitution of monounsaturated or polyunsaturated fat, or both, for saturated fat results in the same fall in LDL-cholesterol concentration as seen with low fat/high carbohydrate diets, it is concluded that low fat/high carbohydrate diets should be avoided in the treatment of syndrome X.

Dietary Carbohydrates↗

Enzyme treatment of exocrine pancreatic insufficiency in chronic pancreatitis.

Exocrine pancreatic insufficiency combined with pancreatic pain and endocrine pancreatic insufficiency are the leading symptoms of chronic pancreatitis. Due to the large functional reserve capacity of the gland, decompensation, i.e. steatorrhea, does not occur before lipase excretion is reduced to < or = 10% of normal. Pancreatic enzyme substitution is indicated when fecal fat excretion exceeds a critical value (normally > 15 g/day) and/or when weight loss is present. A number of studies have dealt with the problems of gastric acid inactivation of pancreatic enzyme preparations as well as their gastric emptying nonsimultaneously with the food. For the present, it is recommended that pancreatic enzyme substitution in patients with proven exocrine pancreatic insufficiency and normal gastric acid secretion be given in multiunit, acid-protected dosages. In patients with gastric hyposecretion and in those who underwent partial or total gastrectomy, enzyme substitution should be administered as granules to enable mixing and simultaneous transport of enzymes with the chyme. The ultimate aim of further scientific and clinical research remains the total abolishment of pancreatic steatorrhea.

Celiac Disease↗

Dietary fat and incidence of type 2 diabetes in older Iowa women.

OBJECTIVE: To examine the associations between reported intakes of dietary fat and incident type 2 diabetes. RESEARCH DESIGN AND METHODS: We studied the relation between dietary fatty acids and diabetes in a prospective cohort study of 35,988 older women who initially did not have diabetes. Diet was assessed with a food frequency questionnaire at baseline, and 1,890 incident cases of diabetes occurred during 11 years of follow-up. RESULTS: After adjusting for age, smoking, alcohol consumption, BMI, waist-to-hip ratio, physical activity, demographic factors, and dietary magnesium and cereal fiber, diabetes incidence was negatively associated with dietary polyunsaturated fatty acids, vegetable fat, and trans fatty acids and positively associated with omega-3 fatty acids, cholesterol, and the Keys score. After simultaneous adjustment for other dietary fat, only vegetable fat remained clearly related to diabetes risk. Relative risks across quintiles of vegetable fat intake were 1.00, 0.90, 0.87, 0.84, and 0.82 (P = 0.02). Diabetes risk was also inversely related to substituting polyunsaturated fatty acids for saturated fatty acids and positively correlated to the Keys dietary score. CONCLUSIONS: These data support an inverse relation between incident type 2 diabetes and vegetable fat and substituting polyunsaturated fatty acids for saturated fatty acids and cholesterol.

Age Factors↗

Effects of protein, monounsaturated fat, and carbohydrate intake on blood pressure and serum lipids: results of the OmniHeart randomized trial.

CONTEXT: Reduced intake of saturated fat is widely recommended for prevention of cardiovascular disease. The type of macronutrient that should replace saturated fat remains uncertain. OBJECTIVE: To compare the effects of 3 healthful diets, each with reduced saturated fat intake, on blood pressure and serum lipids. DESIGN, SETTING, AND PARTICIPANTS: Randomized, 3-period, crossover feeding study (April 2003 to June 2005) conducted in Baltimore, Md, and Boston, Mass. Participants were 164 adults with prehypertension or stage 1 hypertension. Each feeding period lasted 6 weeks and body weight was kept constant. INTERVENTIONS: A diet rich in carbohydrates; a diet rich in protein, about half from plant sources; and a diet rich in unsaturated fat, predominantly monounsaturated fat. MAIN OUTCOME MEASURES: Systolic blood pressure and low-density lipoprotein cholesterol. RESULTS: Blood pressure, low-density lipoprotein cholesterol, and estimated coronary heart disease risk were lower on each diet compared with baseline. Compared with the carbohydrate diet, the protein diet further decreased mean systolic blood pressure by 1.4 mm Hg (P = .002) and by 3.5 mm Hg (P = .006) among those with hypertension and decreased low-density lipoprotein cholesterol by 3.3 mg/dL (0.09 mmol/L; P = .01), high-density lipoprotein cholesterol by 1.3 mg/dL (0.03 mmol/L; P = .02), and triglycerides by 15.7 mg/dL (0.18 mmol/L; P<.001). Compared with the carbohydrate diet, the unsaturated fat diet decreased systolic blood pressure by 1.3 mm Hg (P = .005) and by 2.9 mm Hg among those with hypertension (P = .02), had no significant effect on low-density lipoprotein cholesterol, increased high-density lipoprotein cholesterol by 1.1 mg/dL (0.03 mmol/L; P = .03), and lowered triglycerides by 9.6 mg/dL (0.11 mmol/L; P = .02). Compared with the carbohydrate diet, estimated 10-year coronary heart disease risk was lower and similar on the protein and unsaturated fat diets. CONCLUSION: In the setting of a healthful diet, partial substitution of carbohydrate with either protein or monounsaturated fat can further lower blood pressure, improve lipid levels, and reduce estimated cardiovascular risk. Clinical Trials Registration ClinicalTrials.gov Identifier: NCT00051350.

Adult↗

8-phenyltheophylline as an inhibitor of cyclic AMP hydrolysis by cyclic nucleotide phosphodiesterase.

1. The inhibition, by theophylline and 8-phenyltheophylline, of cAMP hydrolysis by cyclic nucleotide phosphodiesterase from rat fat cells, abdominal aorta, gastrocnemius muscle, erythrocytes and cerebrum was examined. 2. Theophylline was an approximately equieffective inhibitor of cAMP hydrolysis in all tissue extracts. In contrast, 8-phenyltheophylline was a markedly more effective inhibitor of cAMP breakdown in erythrocytes and skeletal muscle than in smooth muscle, brain and fat cells. The 8-phenyl substituted compound was a more potent inhibitor in erythrocytes and skeletal muscle than theophylline. 3. 8-phenyltheophylline has been postulated to be a very selective adenosine receptor antagonist, the present study indicates, that in some tissues 8-phenyltheophylline is not so selective as an adenosine receptor antagonist as has previously been suggested. 4. Analysis of cyclic AMP breakdown by cyclic nucleotide phosphodiesterase in fat cells and erythrocytes demonstrated the presence of high and low affinity forms. 5. Theophylline was slightly more effective as an inhibitor of the high than of the low affinity forms in both tissues. 8-phenyltheophylline was weakly effective as an inhibitor of all isoenzymes from fat cells and selectively inhibited the high affinity phosphodiesterase from erythrocytes. 6. The results suggest that 8-phenyltheophylline is a selective inhibitor of a cyclic nucleotide phosphodiesterase with a high affinity for cAMP, which has relatively greater activity in erythrocytes, and presumably in skeletal muscle, than in other tissues such as fat cells.

3',5'-Cyclic-AMP Phosphodiesterases↗

Effects of chronic peanut consumption on energy balance and hedonics.

OBJECTIVE: To investigate the effects of chronic peanut consumption on energy balance and hedonics. DESIGN: Thirty-week, cross-over, intervention study. Participants were provided 2113+/-494 kJ/day (505+/-118 kcal/day) as peanuts for 8 weeks with no dietary guidance (free feeding-FF), 3 weeks with instructions to add peanuts to their customary diet (addition-ADD) and 8 weeks where peanuts replaced an equal amount of other fats in the diet (substitution-SUB). SUBJECTS: Fifteen, healthy, normal-weight (BMI of 23.3+/-1.8) adults, aged 33+/-9 y. MEASUREMENTS: Dietary intake, appetitive indices, energy expenditure, body weight and hedonics. RESULTS: During FF, peanut consumption elicited a strong compensatory dietary response (ie subjects compensated for 66% of the energy provided by the nuts) and body weight gain (1.0 kg) was significantly lower than predicted (3.6 kg; P<0.01). When customary dietary fat was replaced with the energy from peanuts, energy intake, as well as body weight, were maintained precisely. Participants were unaware that body weight was a research focus. Resting energy expenditure was increased by 11% after regular peanut consumption for 19 weeks (P<0.01). Chronic consumption of peanuts did not lead to a decline in pleasantness or hunger ratings for peanuts nor did it lead to any hedonic shift for selected snack foods with other taste qualities during any of the three treatments. CONCLUSIONS: Despite being energy dense, peanuts have a high satiety value and chronic ingestion evokes strong dietary compensation and little change in energy balance.

Adult↗

Effects of ethanol on lipid metabolism.

Alcohol promotes accumulation of fat in the liver mainly by substitution of ethanol for fatty acids as the major hepatic fuel. The degree of lipid accumulation depends on the supply of dietary fat. Progressive alteration of the mitochondria, which occurs during chronic alcohol consumption, decreases fatty acid oxidation by interfering with citric acid cycle activity. This block is partially compensated for by increased ketone body production, which results in ketonemia. Thus, mitochondrial damage perpetuates fatty acid accumulation even in the absence of ethanol oxidation. Alcohol facilitates esterification of the accumulated fatty acids to triglycerides, phospholipids, and cholesterol esters, all of which accumulate in the liver. The accumulated lipids are disposed of in part as serum lipoprotein, resulting in moderate hyperlipemia. In some individuals with pre-existing alterations of lipid metabolism, small ethanol dose may provoke marked hyperlipemia which responds to alcohol withdrawal. Inhibition of the catabolism of cholesterol to bile salt may contribute to the hepatic accumulation and hypercholesterolemia. The capacity of lipoprotein production and hyperlipemia development increases during chronic alcohol consumption, probably as a result of the concomitant hypertrophy of the endoplasmic reticulum and Golgi apparatus. However, this compensation is relatively inefficient in ridding the liver of fat. This inefficiency may be linked to alterations of hepatic microtubules induced by ethanol or its metabolites, which interfere with the export of protein from liver to serum, promoting hepatic accumulation of proteins as well as fat. As liver injury aggravates, hyperlipemia wanes and liver steatosis is exaggerated. Derangements of serum lipids similar to those found in other types of liver disease also become apparent. The changes in serum lipids may be a sensitive indicator of the progression of liver damage in the alcoholic.

Adipose Tissue↗

Food use and health effects of soybean and sunflower oils.

This review provides a scientific assessment of current knowledge of health effects of soybean oil (SBO) and sunflower oil (SFO). SBO and SFO both contain high levels of polyunsaturated fatty acids (PUFA) (60.8 and 69%, respectively), with a PUFA:saturated fat ratio of 4.0 for SBO and 6.4 for SFO. SFO contains 69% C18:2n-6 and less than 0.1% C18:3n-3, while SBO contains 54% C18:2n-6 and 7.2% C18:3n-3. Thus, SFO and SBO each provide adequate amounts of C18:2n-6, but of the two, SBO provides C18:3n-3 with a C18:2n-6:C18:3n-3 ratio of 7.1. Epidemiological evidence has suggested an inverse relationship between the consumption of diets high in vegetable fat and blood pressure, although clinical findings have been inconclusive. Recent dietary guidelines suggest the desirability of decreasing consumption of total and saturated fat and cholesterol, an objective that can be achieved by substituting such oils as SFO and SBO for animal fats. Such changes have consistently resulted in decreased total and low-density-lipoprotein cholesterol, which is thought to be favorable with respect to decreasing risk of cardiovascular disease. Also, decreases in high-density-lipoprotein cholesterol have raised some concern. Use of vegetable oils such as SFO and SBO increases C18:2n-6, decreases C20:4n-6, and slightly elevated C20:5n-3 and C22:6n-3 in platelets, changes that slightly inhibit platelet generation of thromboxane and ex vivo aggregation. Whether chronic use of these oils will effectively block thrombosis at sites of vascular injury, inhibit pathologic platelet vascular interactions associated with atherosclerosis, or reduce the incidence of acute vascular occlusion in the coronary or cerebral circulation is uncertain. Linoleic acid is needed for normal immune response, and essential fatty acid (EFA) deficiency impairs B and T cell-mediated responses. SBO and SFO can provide adequate linoleic acid for maintenance of the immune response. Excess linoleic acid has supported tumor growth in animals, an effect not verified by data from diverse human studies of risk, incidence, or progression of cancers of the breast and colon. Areas yet to be investigated include the differential effects of n-6- and n-3-containing oil on tumor development in humans and whether shorter-chain n-3 PUFA of plant origin such as found in SBO will modulate these actions of linoleic acid, as has been shown for the longer-chain n-3 PUFA of marine oils.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Concurrent studies of the flow of digesta in the duodenum and of exocrine pancreatic secretion of calves. 3. Further studies on the addition of fat to skim milk and the use of non-milk proteins in milk-substitute diets.

1. The flow of digesta through the duodenum and the concurrent secretion of the pancreas were studied in four Friesian calves given four milk-substitute diets. The diets were: reconstituted, "mildly" pre-heated, spray-dried skim-milk powder with (SKF) or without (SK) margarine fat or with 5o percent of the skim-milk powder in diet SKF replaced by soya-bean flour (ASKF) or fish-protein concentrate (BSKF), together with dried whey. The diets were given ad lib. twice daily from 13 to 37 d of age, each diet being given for 6 consecutive days. Collections of duodenal digesta and pancreatic secretions, from cannulas, were made for 12 h after feeding the 6th and 12th meals ("experimental" meals) for each diet. 2. The diets fed as "experimental" meals contained polyethylene glycol (PEG) as a fluid (whey) marker and goat's milk containing (3H)lysine as a marker for total protein; beta-carotene was added as a lipid marker to the three diets containing margarine fat. 3. Over the 12 h postprandial period, the patterns of duodenal digesta flow and secretion of pancreatic fluid did not differ markedly between the four diets. The abomasal outflow of both nitrogen and lipid in a 12 h postprandial period was related to their intakes from the "penultimate" (5th and 11th) meals for diets SKF and SK BUT TO THEIR INTAKES AT THE "EXPERIMENTAL MEALS" FOR DIETS ASKF and BSKF. Secretion of pancreatic enzyme activity was highest during the 1st hour after feeding but the main outflow from the abomasum of total N and lipid occurred 5-10 h after feeding. 4. The time required for all the whey marker (PEG) to pass through the duodenum was similar for diets SKF and SK, but only 53 and 42 percent respectively of the ingested protein marker passed through the duodenum in the 12 h after feeding. More acid appeared to be secreted by the abomasum when diet SK was given; also less undigested protein passed out of the abomasum after giving this diet. It is concluded that the physical absence of fat globules in the abomasal clot increases the degree of proteolysis. 5. The secretions of pancreatic fluid and pancreatic enzyme activity were all markedly lower for diet SK than for diet SKF. 6. With diets containing non-milk proteins (ASKF and BSKF), abomasal proteolysis was less efficient and the ingested protein passed out of the abomasum more rapidly than for diet SKF. There was no difference in the rate of abomasal outflow of the whey fluids between diets SKF, ASKF and BSKF. 7. In comparison with diet SKF, diets ASKF and BSKF tended to induce less pancreatic enzyme secretion over a 12 h postprandial period, with the exception of lipase. 8. There appeared to be no direct relationship between the quantities of any of the pancreatic enzymes secreted during a postprandial period and either the concurrent flow of duodenal digesta or the total quantities of dietary constituents passing through the duodenum.

Animal Nutritional Physiological Phenomena↗

Thermogenic responses in brown fat cells are fully UCP1-dependent. UCP2 or UCP3 do not substitute for UCP1 in adrenergically or fatty scid-induced thermogenesis.

To examine the thermogenic significance of the classical uncoupling protein-1 (UCP1), the thermogenic potential of brown adipocytes isolated from UCP1-ablated mice was investigated. Ucp1(-/-) cells had a basal metabolic rate identical to wild-type; the mitochondria within them were coupled to the same degree. The response to norepinephrine in wild-type cells was robust ( approximately 10-fold increase in thermogenesis); Ucp1(-/-) cells only responded approximately 3% of this. Ucp1(-/-) cells were as potent as wild-type in norepinephrine-induced cAMP accumulation and lipolysis and had a similar mitochondrial respiratory complement. In wild-type cells, fatty acids induced a thermogenic response similar to norepinephrine, but fatty acids (and retinoate) were practically without effect in Ucp1(-/-) cells. It is concluded that no other adrenergically induced thermogenic mechanism exists in brown adipocytes except that mediated by UCP1 and that entopic expression of UCP1 does not lead to overt innate uncoupling, and it is suggested that fatty acids are transformed to an intracellular physiological activator of UCP1. High expression of UCP2 and UCP3 in the tissue was not associated with an overt innate highly uncoupled state of mitochondria within the cells, nor with an ability of norepinephrine or endo- or exogenous fatty acids to induce uncoupled respiration in the cells. Thus, UCP1 remains the only physiologically potent thermogenic uncoupling protein in these cells.

Adipocytes↗