Suppression of hepatic fatty acid synthase by feeding alpha-linolenic acid rich perilla oil lowers plasma triacylglycerol level in rats

This study was performed to determine the effects of dietary perilla oil, a n-3 alpha-linolenic acid (ALA) source, on hepatic lipogenesis as a possible mechanism of lowering triacylglycerol (TG) levels. Male Sprague-Dawley rats were trained for a 3-hour feeding protocol and fed one of five semipurified diets as follows: 1% (w/w) corn oil control diet, or one of four diets supplemented with 10% each of beef tallow, corn oil, perilla oil, and fish oil. Two separate experiments were performed to compare the effects of feeding periods, 4 weeks and 4 days. Hepatic and plasma TG levels were decreased in rats fed perilla oil and fish oil diets, compared with corn oil and beef tallow diets. The activities of hepatic lipogenic enzymes such as fatty acid synthase (FAS), glucose-6-phosphate dehydrogenase, and malic enzyme were suppressed in the fish oil, perilla oil, and corn oil-fed groups, and the effect was the most significant in the fish oil-fed group. Also, the activities of glycolytic enzymes, glucokinase, and L-pyruvate kinase showed the similar trend as that of lipogenic enzymes. The activity of FAS, the key regulatory enzyme in lipogenesis, was positively correlated with hepatic and plasma TG levels and reduced significantly in the perilla oil-fed group compared with corn oil-fed group. In addition, the FAS activity was negatively correlated with the hepatic microsomal content of EPA and DHA. In conclusion, suppression of FAS plays a significant role in the hypolipidemic effects observed in rats fed ALA rich perilla oil and these effects were associated with the increase of hepatic microsomal EPA and DHA contents.     

Lipoprotein lipase and lipogenic enzyme activities in adipose tissue from rats fed different lipid sources

This work was designed to study the effect of different lipid sources on the activities of lipoprotein lipase and lipogenic enzymes in adipose tissue from rats fedad libitum or energy-controlled diets. Male Wistar rats were fed diets containing 40% of energy as fat (olive oil, sunflower oil, palm oil or beef tallow), for 4 wk. Underad libitum feeding no differences were found among dietary fat groups in final body weight, adipose tissue weights and total body fat. Under energy-controlled feeding, despite isoenergetic intake, rats fed the beef tallow diet gained significantly less weight than rats fed the other three diets. Beef tallow fed rats showed the lowest values for adipose tissue weights and total body fat. When rats had free access to food no effect of dietary lipid source on lipogenic enzyme activities was found. In contrast, under energy-controlled feeding rats fed the beef tallow diet showed significantly higher activities of glucose-6-phosphate dehydrogenase and fatty acid synthase than rats fed the other three diets. Heparin-releasable lipoprotein lipase activity in perirenal and subcutaneous adipose tissues was not different among rats fed olive oil, safflower oil, palm oil or beef tallow. When comparing both adipose tissue anatomical locations, significantly higher activities were found in subcutaneous than in perirenal fat pad independently of dietary fat. In conclusion, under our experimental protocol, lipogenesis in rat adipose tissue does not seem to be affected by dietary fat type.     

Suppression of fatty acid synthase by dietary polyunsaturated fatty acids is mediated by fat itself,not by peroxidative mechanism

This study examined the effect of dietary polyunsaturated fatty acids (PUFA) that were supplemented with vitamin E on lipid peroxidation, glutathione-dependent detoxifying enzyme system activity, and lipogenic fatty acid synthase (FAS) expression in rat liver. Male Sprague-Dawley rats were fed semipurified diets containing either 1% (w/w) corn oil or 10% each of beef tallow, corn oil, perilla oil, and fish oil for 4 wk. Alpha-tocopherol was supplemented in perilla oil (0.015%) and fish oil (0.019%). Hepatic thiobarbituric acid reactive substances, an estimate of lipid peroxidation, were not significantly different among the dietary groups. The glutathione peroxidase, glutathione reductase, and glutathione S-transferase activities were all elevated by the polyunsaturated fats, especially fish oil. The activity of FAS was reduced in the polyunsaturated fat-fed groups in the order of fish oil, perilla oil, and corn oil. The mRNA contents decreased in rats that were fed the 10% fat diets, particularly polyunsaturated fats, compared with the rats that were fed the 1% corn oil diet. Similarly, the inhibitory effect was the greatest in fish oil. These results suggest that lipid peroxidation can be minimized by vitamin E; PUFA in itself has a suppressive effect on lipogenic enzyme.     

Stimulation of acyl-CoA oxidase by alpha-linolenic acid-rich perilla oil lowers plasma triacylglycerol level in rats

The effect of dietary polyunsaturated fatty acids (PUFA) on hepatic peroxisomal oxidation was investigated with respect to the postprandial triacylglycerol levels. Male Sprague--Dawley rats were fed semipurified diets containing either 1% (w/w) corn oil, or 10% each of beef tallow, corn oil, perilla oil, and fish oil for 4 weeks and 4 days. Hepatic and plasma triacylglycerol levels were reduced in rats fed fish and perilla oil diets compared with corn oil and beef tallow diets. The peroxisomal beta-oxidation, catalase activity, and acyl-CoA oxidase (AOX) activity were markedly increased by fish oil feeding. To a lesser extent, perilla oil elevated AOX activity in a 4-day feeding although the effect gradually decreased in a 4-week feeding. Similarly, the mRNA levels were increased in rats fed fish and perilla oils. AOX activity was negatively correlated with postprandial triacylglycerol levels. In addition, the stimulation of AOX was highly associated with the content of long chain n-3 PUFA such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in hepatic microsome. These effects were evident within 4 days of initiating feeding. Therefore, alpha-linolenic perilla oil exerts a similar effect to fish oil in stimulating hepatic activity and gene expression of AOX by enriching long chain n-3 PUFA in hepatic membrane fraction, which can partly account for the reduction of postprandial triglyceridemia.     

Effects of stearic acid and beef tallow on iron utilization by the rat.

Two experiments were done in which anemic rats were fed diets containing safflower oil or stearic acid and low (10 ppm) or adequate (39-42 ppm) iron. Diets were 24% fat by weight. In the stearic acid diets, 2% (Experiment 1) or 4% (Experiment 2) of the fat was supplied by safflower oil to satisfy essential fatty acid requirements. Repletion of hemoglobin, hematocrit, and liver iron was assessed. Compared with safflower oil in both experiments, stearic acid had a significant positive effect (P less than 0.0001) on repletion of hemoglobin (Hb), hematocrit (Hct), and liver iron concentration; the effect on Hb and Hct was most pronounced when dietary iron was low. When expressed as g Hb/mg Fe intake, Hb repletion was affected by a significant interaction between fat and Fe (P less than 0.002) and was greatest in rats fed low iron stearic acid diets. In a third experiment, rats were fed low dietary iron and 24% safflower oil, 20% stearic acid + 4% safflower oil, 3.2% stearic acid + 20.8% safflower oil, or 20% beef tallow + 4% safflower oil. The 20% beef tallow provided 3.2% stearic acid in the total diet. The response of Hb and Hct were similar to those in the first two experiments for rats fed safflower oil or stearic acid. Rats fed beef tallow had significantly greater (P less than 0.05) Hb and Hct repletion than did rats fed safflower oil, although the degree of repletion was less than that observed in rats fed 20% stearic acid. There was no difference in iron repletion of rats fed 3.2% stearic acid and rats fed beef tallow. We conclude that stearic acid enhances iron utilization by rats.     

The effects of diet on the esterification of glycerol phosphate, dihydroxyacetone phosphate and 2-hexadecylglycerol by homogenates of rat adipose tissue.

1. Male rats were fed for 5 weeks after weaning on a diet containing (by weight) 59% of starch or on diets that contained 39% of starch and 20% of either sucrose, beef tallow or corn oil. 2. The rats fed on the beef tallow consumed more energy than did the rats fed on the starch and sucrose diets. The rats fed on the corn oil drank less water than did the other groups of rats. 3. There were no significant differences between the four groups in terms of body-weight gain, epididymal-fat-pad weight and in the size, number and triacylglycerol content of the adipocytes in the fat-pads. 4. There was a significant correlation (P less than 0.001) between the activities of glycerol phosphate acyltransferase and monoacylglycerol acyltransferase in individual rats. Both of these activities were highest in the group fed on the high-starch diet and both correlated with the consumption of glucose by individual rats in the four groups. 5. The percentage of glycerol phosphate converted into diacylglycerol and triacylglycerol was positively correlated with the mean diameters, surface area and triacylglycerol content of the adipocytes for individual rats and was greates in the sucrose-fed rats. 6. The specific activity of dihydroxyacetone phosphate acyltransferase was highest in the rats fed on beef tallow. This activity was positively correlated with the energy intake for all dietary groups over the 5-week feeding period. 7. The results are discussed in terms of the functions of the three routes of glycerolipid synthesis in adipose tissue.     

Altered mRNA expression of hepatic lipogenic enzyme and PPARalpha in rats fed dietary levan from Zymomonas mobilis

Levan or high molecular beta-2,6-linked fructose polymer is produced extracellularly from sucrose-based substrates by bacterial levansucrase. In the present study, to investigate the effect of levan feeding on serum leptin, hepatic lipogenic enzyme and peroxisome proliferation-activated receptor (PPAR) alpha expression in high-fat diet-induced obese rats, 4-week-old Sprague-Dawley male rats were fed high-fat diet (beef tallow, 40% of calories as fat), and, 6 weeks later, the rats were fed 0%, 1%, 5% or 10% levan-supplemented diets for 4 weeks. Serum leptin and insulin level were dose dependently reduced in levan-supplemented diet-fed rats. The mRNA expressions of hepatic fatty acid synthase and acetyl CoA carboxylase, which are the key enzymes in fatty acid synthesis, were down-regulated by dietary levan. However, dietary levan did not affect the gene expression of hepatic malic enzyme, phosphatidate phosphohydrolase and HMG CoA reductase. Also, the lipogenic enzyme gene expression in the white adipose tissue (WAT) was not affected by the diet treatments. However, hepatic PPARalpha mRNA expression was dose dependently up-regulated by dietary levan, whereas PPARgamma in the WAT was not changed. The results suggest that the in vivo hypolipidemic effect of dietary levan, including anti-obesity and lipid-lowering, may result from the inhibition of lipogenesis and stimulation of lipolysis, accompanied with regulation of hepatic lipogenic enzyme and PPARalpha gene expression.     

Long-term feeding of various fat diets modulates azoxymethane-induced colon carcinogenesis through Wnt/beta-catenin signaling in rats

The Wnt signaling pathway plays an essential role in carcinogenesis, and the amount of fat intake and composition of dietary fatty acids are crucial factors for colon carcinogenesis. We investigated whether various dietary fats affected the Wnt signaling pathway of colon tumorigenesis in azoxymethane (AOM)-treated rats. Male Sprague-Dawley rats were given intraperitoneal injections of AOM and supplemented with 10% corn, olive, beef, and fish oil for 44 wk. Aberrant crypt foci (ACF) and tumors were examined at 12 and 44 wk. Normal appearing colon mucosal proliferation and apoptosis were evaluated by 5-bromo-2'-deoxyuridine (BrdU) incorporation and percentages of fragmented DNA, respectively. Expressions of beta-catenin, cyclin D(1), Wnt2, Wnt3, and Wnt5a of normal appearing colon mucosa were analyzed by Western blot analysis. Long-term dietary corn oil and beef tallow increased ACF, tumor incidence, and tumor numbers in AOM-treated rats. In contrast, both olive and fish oil inhibited them. Dietary corn oil and beef tallow increased BrdU incorporation and the expression of cytosolic beta-catenin and cyclin D(1) and decreased apoptosis in the colon mucosa. Expressions of Wnt2 and Wnt3 in rats fed with beef tallow and Wnt5a in rats fed with corn oil increased with or without AOM-treatment. BrdU-incorporated cells were often observed at the tops of crypts in rats fed with beef tallow, whereas this was not observed in rats fed with the other diet. Long-term high intake of corn oil and beef tallow enhanced cell proliferation through Wnt signaling and modulated the distribution of proliferating cells, which might contribute to promoting effects in colon tumorigenesis.     

Fish oil reduces cholesterol and arachidonic acid content more efficiently in rats fed diets containing low linoleic acid to saturated fatty acid ratios

Rats were fed diets containing a high level of saturated fatty acids (hydrogenated beef tallow) versus a high level of linoleic acid (safflower oil) at both low and high levels of fish oil containing 7.5% (w/w) eicosapentaenoic and 2.5% (w/w) docosahexaenoic acids for a period of 28 days. The effect of feeding these diets on the cholesterol content and fatty acid composition of serum and liver lipids was examined. Feeding diets high in fish oil with safflower oil decreased the cholesterol content of rat serum, whereas feeding fish oil had no significant effect on the cholesterol content of serum when fed in combination with saturated fatty acids. The serum cholesterol level was higher in animals fed safflower oil compared to animals fed saturated fat without fish oil. Consumption of fish oil lowered the cholesterol content of liver tissue regardless of the dietary fat fed. Feeding diets containing fish oil reduced the arachidonic acid content of rat serum and liver lipid fractions, the decrease being more pronounced when fish oil was fed in combination with hydrogenated beef tallow than with safflower oil. These results suggest that dietary n-3 fatty acids of fish oil interact with dietary linoleic acid and saturated fatty acids differently to modulate enzymes of cholesterol and fatty acid metabolism.     

Interactions of saturated, n-6 and n-3 polyunsaturated fatty acids to modulate arachidonic acid metabolism

Anti-thrombotic effects of omega-3 (n-3) fatty acids are believed to be due to their ability to reduce arachidonic acid levels. Therefore, weanling rats were fed n-3 acids in the form of linseed oil (18:3n-3) or fish oil (containing 20:5n-3 and 22:6n-3) in diets containing high levels of either saturated fatty acids (hydrogenated beef tallow) or high levels of linoleic acid (safflower oil) for 4 weeks. The effect of diet on the rate-limiting enzyme of arachidonic acid biosynthesis (delta 6-desaturase) and on the lipid composition of hepatic microsomal membrane was determined. Both linseed oil- or fish oil-containing diets inhibited conversion of linoleic acid to gamma-linolenic acid. Inhibition was greater with fish oil than with linseed oil, only when fed with saturated fat. delta 6-Desaturase activity was not affected when n-3 fatty acids were fed with high levels of n-6 fatty acids. Arachidonic acid content of serum lipids and hepatic microsomal phospholipids was lower when n-3 fatty acids were fed in combination with beef tallow but not when fed with safflower oil. Similarly, n-3 fatty acids (18:3n-3, 20:5n-3, 22:5n-3, and 22:6n-3) accumulated to a greater extent when n-3 fatty acids were fed with beef tallow than with safflower oil. These observations indicate that the efficacy of n-3 fatty acids in reducing arachidonic acid level is dependent on the linoleic acid to saturated fatty acid ratio of the diet consumed.     

Isocaloric manipulation of macronutrients within a high-carbohydrate/moderate-fat diet induces unique effects on hepatic lipogenesis,steatosis and liver injury

Diets containing excess carbohydrate and fat promote hepatic steatosis and steatohepatitis in mice. Little is known, however, about the impact of specific carbohydrate/fat combinations on liver outcome. This study was designed to determine whether high-energy diets with identical caloric density but different carbohydrate and fat composition have unique effects on the liver. Four experimental diets were formulated with 60% kcal carbohydrate and 20% kcal fat, each in nearly pure form from a single source: starch-oleate, starch-palmitate, sucrose-oleate and sucrose-palmitate. The diets were fed to mice for 3 or 12 weeks for analysis of lipid metabolism and liver injury. All mice developed hepatic steatosis over 12 weeks, but mice fed the sucrose-palmitate diet accumulated more hepatic lipid than those in the other three experimental groups. The exaggerated lipid accumulation in sucrose-palmitate-fed mice was attributable to a disproportionate rise in hepatic de novo lipogenesis. These mice accrued more hepatic palmitate and exhibited more evidence of liver injury than any of the other experimental groups. Interestingly, lipogenic gene expression in mice fed the custom diets did not correlate with actual de novo lipogenesis. In addition, de novo lipogenesis rose in all mice between 3 and 12 weeks, without feedback inhibition from hepatic steatosis. The pairing of simple sugar (sucrose) and saturated fat (palmitate) in a high-carbohydrate/moderate-fat diet induces more de novo lipogenesis and liver injury than other carbohydrate/fat combinations. Diet-induced liver injury correlates positively with hepatic de novo lipogenesis and is not predictable by isolated analysis of lipogenic gene expression.     

Fat metabolism is regulated by altered gene expression of lipogenic enzymes and regulatory factors in liver and adipose tissue but not in semimembranosus muscle of pigs during the fattening period

It has been shown previously that lipid metabolism is regulated by fatty acids (FA) and that thyroid hormones are important regulators of energy metabolism. The effects of weight, dietary fat level and dietary FA profile on thyroid hormone levels and expression of lipogenic genes and tissue FA composition were studied. Sixty-one crossbred gilts weighing 62 ± 5.2 kg BW average were either slaughtered at the beginning of the trial (n = 5) or fed one of seven diets (n = 8 pigs per diet): a semi-synthetic diet formulated to contain a very low level of fat (NF) and six diets based on barley-soybean meal supplemented with approximately 10% fat of different origin and slaughtered at 100 kg BW. The supplemental fats were tallow, high-oleic sunflower oil, sunflower oil (SFO), linseed oil, fat blend (55% tallow, 35% sunflower oil, 10% linseed oil) and fish oil blend (40% fish oil, 60% linseed oil). In general, the dietary FA profiles altered the FA composition of liver, semimembranosus muscle and adipose tissues. Pigs fed the NF diet had the highest free and total triiodothyronine (T3) values followed by pigs fed SFO. Total T3 levels were higher in pigs at 60 kg than in pigs at 100 kg. Correlations between thyroid hormones and genes encoding enzymes of fat synthesis in adipose tissue (acetyl CoA carboxylase (ACACA), fatty acid synthase and stearoyl CoA desaturase (SCD)) and the large differences in expression of lipogenic genes at different weights (60 and 100 kg BW), suggest a role for thyroid hormones and for T3, in particular, in regulating whole animal fat metabolism, with effects brought about by altered expression of lipogenic genes. Liver sterol receptor element binding protein-1 (SREBP1) mRNA content was affected by dietary treatment (P < 0.001) and was correlated with ACACA and SCD, whereas adipose tissue SREBP1 was not correlated with the mRNA abundance of any lipogenic enzyme. Weight and tissue factors showed greater influence on mRNA abundance of genes related with lipid metabolism than diet and tissue FA composition. In the pig, FA synthesis appear to be of greater magnitude in adipose tissue than in the liver as suggested by the higher expression of lipogenic genes in adipose tissue.     

Increased hepatic activity of inducible nitric oxide synthase in rats fed on a high-fat diet

The effects were examined of the dietary level of fat on the activity of inducible nitric oxide synthase (iNOS) in the liver of rats. In experiment 1, rats were fed on a diet containing 5% or 20% beef tallow or safflower oil for 32 d. The animals were given a subcutaneous injection of the carcinogen, 1,2-dimethylhydrazine (DMH), on d 4. The activity of hepatic iNOS was significantly elevated by the high-fat diet, but was unaffected by the dietary source of the fat examined. In experiment 2, rats were fed on a 5% or 20% beef tallow diet for 11 d or 32 d with or without the DMH treatment. Feeding the high-fat diet and DMH treatment caused higher activity of hepatic iNOS. In experiment 3, the high-fat diet elevated hepatic iNOS activity and the amount of its protein in the lipopolysaccharide-treated rats. The results suggest that hepatic NO production is enhanced by a high-fat diet.     

A comparison of extrahepatic lipogenesis from a small glucose meal in obob and gold thioglucose obese mice fed low- or high-fat diets with or without the addition of Delta22-5beta-taurocholenic acid

Extrahepatic fatty acid synthesis from a 250 mg meal of [U-(14)C]-glucose was measured in epidymal fat pads and the remaining carcass of hyperglycemic obese (obob), gold thioglucose obese, and nonobese controls under conditions of maximum and minimum lipogenesis. Also assessed was the effect of Delta(22)-5beta-taurocholenic acid, previously shown to inhibit hepatic fatty acid synthesis. Both types of obese and nonobese mice were fed for 6 weeks glucose-based diets containing either 1% corn oil or 40% lard with or without the addition of 0.05% taurocholenic acid. In mice fed 1% corn oil, incorporation of labeled glucose into carcass fatty acids was 25% greater in nonobese than obese mice of either type of obesity. On this diet incorporation of labeled glucose into epididymal fatty acids was reduced 83% in hyperglycemic obese mice compared with nonobese littermates. The corresponding reduction in lipogenesis in gold thioglucose obese mice was only 23% compared with nonobese controls. Feeding 40% lard reduced incorporation of labeled glucose into epididymal and carcass fatty acid 67 to 95% compared with mice fed 1% corn oil in both types of obese and nonobese mice whether or not taurocholenic acid had been fed. Both types of obesity or feeding 40% lard reduced lipogenesis in fat pads to a greater extent than glucose uptake by the pads with the reductions additive. Feeding taurocholenic acid reduced pad weight 30% across strain and obesity status, increased uptake of labeled glucose into epididymal fat pads and increased the percentage of the labeled glucose in the pad recovered as fatty acid in both types of obese and nonobese mice when the diet was 1% corn oil. Similarities and differences between the two obesity models are discussed.     

Comparison of high-protein diets and leucine supplementation in the prevention of metabolic syndrome and related disorders in mice

High-protein diets have been shown to promote weight loss, to improve glucose homeostasis and to increase energy expenditure and fat oxidation. We aimed to study whether leucine supplementation is able to mimic the alleviating effects of high-protein diets on metabolic syndrome parameters in mice fed high-fat diet.Male C57BL/6 mice were fed for 20 weeks with semisynthetic high-fat diets (20% w/w of fat) containing either an adequate (10% protein, AP) or high (50% protein, HP) amount of whey protein, or an AP diet supplemented with l-leucine corresponding to the leucine content of the HP diet (6% leucine, AP+L). Body weight and composition, energy expenditure, glucose tolerance, hepatic triacylglycerols (TG), plasma parameters as well as expression levels of mRNA and proteins in different tissues were measured. HP feeding resulted in decreased body weight, body fat and hepatic TG accumulation, as well as increased insulin sensitivity compared to AP. This was linked to an increased total and resting energy expenditure (REE), decreased feed energy efficiency, increased skeletal muscle (SM) protein synthesis, reduced hepatic lipogenesis and increased white fat lipolysis. Leucine supplementation had effects that were intermediate between HP and AP with regard to body composition, liver TG content, insulin sensitivity, REE and feed energy efficiency, and similar effects as HP on SM protein synthesis. However, neither HP nor AP+L showed an activation of the mammalian target of rapamycin pathway in SM. Leucine supplementation had no effect on liver lipogenesis and white fat lipolysis compared to AP. It is concluded that the essential amino acid leucine is able to mimic part but not all beneficial metabolic effects of HP diets.     

Dietary fat modifies the in vivo mutagenicity of some food-borne carcinogens

Female BALB/c mice were fed a low fat diet (1% safflower oil, by weight) or one supplemented with 25% (by weight) of beef fat or olive oil. The abilities of these diets to modify the in vitro and in vivo hepatic conversion of the dietary carcinogens aflatoxin B1, 2-amino-3, 4-dimethylimidazo[4,5-f]quinoline (MeIQ) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) to bacterial mutagens was evaluated. Dietary olive oil appeared to increase the metabolism of both MeIQ and Trp-P-2 to bacterial mutagens in vivo using the intrasanguineous host-mediated assay. Feeding mice either of the high-fat diets increased hepatic conversion of these two compounds to bacterial mutagens in vitro. Dietary fat had no effect on the metabolism of aflatoxin B1. Subsequent experiments suggested that the in vivo effects of dietary olive oil on MeIQ and Trp-P-2 mutagenesis were due to the induction of hepatic enzyme activities rather than to increased rates of uptake of the carcinogen from the gut-lumen.     

Fish oil prevents effect of high cholesterol diet on active intestinal transport of galactose

We tested the hypothesis that diets containing fish oils prevent the effects of a high cholesterol diet on the morphology and nutrient uptake of the intestine. Isocaloric semisynthetic diets were supplemented with beef tallow or fish oil containing low or high amounts of cholesterol and were fed to growing female Wistar rats for 14 days, after which the in vitro jejunal and ileal uptake of glucose, galactose, long-chain fatty acids, and cholesterol was determined. Feeding cholesterol with beef tallow was associated with a 12% decrease in the jejunal mucosal surface area. Feeding fish oil decreased jejunal mucosal surface area by 24%, as compared with the beef tallow diet, but the reduction was increased to 42% when fish oil and cholesterol were fed together. Ileal surface area was unaffected by varying the major source of dietary lipid, or by adding cholesterol. Despite the effect of fish oil on the mucosal surface area, the jejunal and ileal uptake of saturated as well as unsaturated long-chain fatty acids and cholesterol was similar in the four diet groups. Cholesterol supplementation enhanced the jejunal uptake of high concentrations of galactose only when fed with beef tallow, i.e., feeding fish oil prevented the enhancing effect of cholesterol on galactose uptake observed when beef tallow was fed. Thus, (i) a fish oil diet prevents the enhancing effect of cholesterol on jejunal active transport of galactose, an effect not explained by the reduction in jejunal mucosal surface area observed with the fish oil diet; (ii) these dietary manipulations result in a clear dissociation of the morphological from the transport adaptation of the intestine; and (iii) substitution of fish oil for beef tallow as the major source of lipid in the diet prevents the influence of cholesterol on the active intestinal transport of galactose.     

The mouse bioassay for the detection of estrogenic activity in rodent diets: III. Stimulation of uterine weight by dextrose, sucrose and corn starch

We have shown previously that mice fed the American Institute of Nutrition (AIN-76A) purified diet experience a significant increase in uterine:body weight (U:BW) ratios when compared to the U:BW ratios of mice fed a closed formula natural ingredient diet (Certified Rodent Chow #5002) for 7 days. The AIN-76A purified diet contains 5% corn oil and 65% carbohydrates with 50% of the carbohydrates coming from sucrose or dextrose and 15% from corn starch. The objective of this study was to determine whether the fat and carbohydrate content contributed to the unexpected uterine growth promoting activity observed in mice fed the AIN-76A diet. Estrogen bioassays were performed using CD-1 mice weaned at 15 days of age and assigned randomly to the negative control diet (Certified Rodent Chow #5002) or to the positive control diet (#5002) containing 4 or 6 ppb DES for comparison or to the test diets. The test diets were prepared by adding sucrose, dextrose, corn starch, corn oil or soybean oil to the #5002 negative control diet at 10% w/w concentration. Uterine:BW ratios were determined at 7 days post-feeding. The uterine weights and the U:BW ratios of mice fed the test diets containing dextrose, corn starch, or corn oil, were increased significantly (P less than 0.05) over those of mice fed the negative control diet. The uterine weights and U:BW ratios of mice fed the test diets containing sucrose or soybean oil also were increased over those of mice fed the negative control diet. These increases in uterine weights and U:BW ratios were similar to the increases in uterine weights and U:BW ratios of mice fed the positive control diet containing 4 ppb DES. It was concluded that the fats and carbohydrates caused preferential increases in uterine weights and in U:BW ratios and may account for the estrogen-like uterine growth promoting activity observed in mice fed the AIN-76A purified diet.     

Hepatic and adipose tissue lipogenic enzyme mRNA levels are suppressed by high fat diets in the rat

Small changes in lipogenic enzyme activity induced by dietary fats of different composition may, over the long term, have significant impact on the development of obesity. We have investigated the effect of high fat diets (45% of calories as fat) on abundance of mRNA encoding fatty acid synthetase (FAS) and glycerophosphate dehydrogenase (GPDH) in male Sprague-Dawley rats. When caloric intake was equal, the relative amount of hepatic FAS mRNA was greater in rats fed a saturated compared to a polyunsaturated fat diet. This difference could not be attributed to diet-induced changes in plasma insulin concentration. However, both fat diets suppressed hepatic FAS mRNA compared to a sucrose diet. Close correlation between FAS specific activity and the relative amount of mRNA suggested that regulation was mainly at a pre-translational level. Adipose tissue FAS mRNA was suppressed by the two fat diets equally while GPDH mRNA was unaffected by dietary composition. Retroperitoneal fat pads were significantly larger in rats fed saturated compared to those fed polyunsaturated fat for 26 weeks. We concluded that dietary saturated fats fail to suppress hepatic de novo lipogenesis as effectively as polyunsaturated fats, which may have implications for the prevention of obesity in humans.     

Short chain fatty acids may improve hepatic mitochondrial energy efficiency in heat stressed-broilers

The present study was conducted to investigate the effects of four dietary fat types and two environmental temperatures on the hepatic mitochondrial energetic in male broilers exposed to heat stress. The birds were kept in two separate rooms at 24 °C or 36 °C from 32 to 42 d of age with four experimental groups in each room. The birds fed on the diets supplemented containing rich sources of long-chain saturated fatty acids (beef tallow), middle-length-chain saturated FA (coconut oil), monounsaturated FA (olive oil), or polyunsaturated FA (soybean oil) for ten days. At 36 °C, the highest body weight and lowest feed conversion ratio were recorded in the birds fed on the diets supplemented with coconut oil or beef tallow. Temperature and fat type significantly affected the activities of the mitochondrial electron transport chain complexes (P < 0.01). There was a significant interaction between the temperature and fat type (P < 0.01). Generally, electron transport chain complexes I–V enzymatic activities were decreased at 36 °C. The coconut oil-fed birds showed the highest complex I activity at both temperatures. The beef tallow-fed broilers showed the lowest complex II activity at 24 °C. In birds exposed to 36 °C, complex II activity was higher for birds fed saturated coconut oil or beef tallow than those feeding the unsaturated olive oil or soybean oil-supplemented diets. At 24 °C, the highest and lowest complex III activities were recorded for the coconut oil- and beef tallow-supplemented diets, respectively. At 36 °C, the activity of complex III was coconut oil > beef tallow > olive oil > soybean oil. At 24 °C, complex IV activity was highest in coconut oil- or soybean oil-fed broilers; and at 36 °C, complex IV showed the lowest activity in soybean oil-fed birds. The highest complex IV activity was observed in coconut oil-fed chickens followed by olive oil-fed and beef tallow-fed birds, respectively. At 24 or 36 °C, the highest and lowest complex V activity was observed in coconut oil-fed and soybean oil-fed chickens, respectively. ATP concentration and mitochondrial membrane potential were in the order of coconut oil > beef tallow > olive oil > soybean oil at both temperatures. Temperature and fat type significantly affected the avANT mRNA concentration. Exposure of broilers to 36 °C generally decreased the mRNA expression of avANT, with beef tallow- or coconut oil-supplemented birds showing a lower avANT mRNA expression than those receiving olive oil- or soybean oil-supplemented diets. These findings provide further information on the use of fat sources in the diet of heat stressed-broilers.