Saturated Fatty Acid-rich Diet Research Articles

Study models for inducing tumors by 7,12-dimethylbenz (A) - Antracene in rat mammary gland

Five study models (A, B, C, D, E) were used to investigate the effect of 7, 12-dimethylbenz(a)anthracene in inducing tumors in the mammary tissue of Spreague-Dawiey rats. Each group was subjected ad libitum to the foiiowing diets: group A - commercial ration; groups B/C - a semipurified linoleic acid-rích diet; group D - a semipurified saturated fatty acid-rich diet; group E - a semipurified fat diet composed of 50% soybean 0ff (rich in essential fatty acid), 25% olive oil (rich in oleic acid) and 25% coconut oil (rich in saturated fatty acid). The animais were fed through intragastric instiiation, one or two doses of DMBA dissolved in 1 ml of soybean oil Group A animais received a single 10 mg-DMBA-doses 60 days after birth. Group 8 animals received two-20 mg-DMBA -doses, the first dose 45 days after birth and the second 60 days after birth. Groups C, D and E animais were treated in the same way as group 8 animais. The control-groups were fed 1 mi-piacebo-soybean oiL DMBA induced tumors in the treated rats as visualized in the following results: 1) Groups A, B, C, O and E developed 52%, 76%, 88%, 60% and 67% tumors, respectively; 2) in the test groups A, B, C, D and E the first paipabie tumor was reported at 200 ± 52, 103 ± 36, 48 ± 1, 133 ± 62 and 183 ± 45 days after DMBA administration, respectively. 3) 14.8%, 40.7%, 97.5%, 50.0% and 41.7% of all tumors were classified as adenocarcinoma.The results suggest that study model "C" was the most effective one, inducing higher incidence of adenocarcinomas in DMBA-treated-rats, the symptons being evidenced in the shortest experimental time.

Exploring body weight-influencing gut microbiota by elucidating the association with diet and host gene expression

We aimed to identify gut microbiota that influences body weight by elucidating the association with diets and host genes. Germ-free (GF) mice with and without fecal microbiota transplant (FMT) were fed a normal, high-carbohydrate, or high-fat diet. FMT mice exhibited greater total body weight; adipose tissue and liver weights; blood glucose, insulin, and total cholesterol levels; and oil droplet size than the GF mice, regardless of diet. However, the extent of weight gain and metabolic parameter levels associated with gut microbiota depended on the nutrients ingested. For example, a disaccharide- or polysaccharide-rich diet caused more weight gain than a monosaccharide-rich diet. An unsaturated fatty acid-rich diet had a greater microbial insulin-increasing effect than a saturated fatty acid-rich diet. Perhaps the difference in microbial metabolites produced from substances taken up by the host created metabolic differences. Therefore, we analyzed such dietary influences on gut microbiota, differentially expressed genes between GF and FMT mice, and metabolic factors, including body weight. The results revealed a correlation between increased weight gain, a fat-rich diet, increased Ruminococcaceae abundance, and decreased claudin 22 gene expression. These findings suggest that weight regulation might be possible through the manipulation of the gut microbiota metabolism using the host’s diet.

A saturated fatty acid-rich diet enhances hepatic lipogenesis and tumorigenesis in HCV core gene transgenic mice

Previous studies suggested that high consumption of saturated fatty acid (SFA) is a risk factor for liver cancer. However, it remains unclear how dietary SFA affects liver tumorigenesis. This study aimed to investigate the impact of a SFA-rich diet on hepatic tumorigenesis using hepatitis C virus core gene transgenic (HCVcpTg) mice that spontaneously developed hepatic steatosis and tumors with aging. Male HCVcpTg mice were treated for 15 months with a purified control diet or SFA-rich diet prepared by replacing soybean oil in the control diet with hydrogenated coconut oil, and phenotypic changes were assessed. In this special diet, almost all dietary fatty acids were SFA. Long-term feeding of SFA-rich diet to HCVcpTg mice increased hepatic steatosis, liver dysfunction, and the prevalence of liver tumors, likely due to stimulation of de novo lipogenesis, activation of the pro-inflammatory and pro-oncogenic transcription factor nuclear factor-kappa B (NF-κB), enhanced c-Jun N-terminal kinase/activator protein 1 (JNK/AP-1) signaling and induction of the oncogenes cyclin D1 and p62/sequestosome 1. The SFA-rich diet did not affect liver fibrosis or autophagy. Collectively, long-term SFA-rich diet consumption promoted hepatic tumorigenesis mainly through activation of lipogenesis, NF-κB, and JNK/AP-1 signaling. We therefore propose that HCV-infected patients should avoid excessive intake of SFA-rich foods to prevent liver cancer.

Disentangling the Effects of Monounsaturated Fatty Acids from Other Components of a Mediterranean Diet on Serum Metabolite Profiles: A Randomized Fully Controlled Dietary Intervention in Healthy Subjects at Risk of the Metabolic Syndrome.

ScopeThe Mediterranean (MED) diet has been associated with a decreased risk of cardiovascular diseases. It is unclear whether this health effect can be mainly contributed to high intakes of monounsaturated fatty acids (MUFA), characteristic for the MED diet, or whether other components of a MED diet also play an important role.Methods and ResultsA randomized fully controlled parallel trial is performed to examine the effects of the consumption of a saturated fatty acid rich diet, a MUFA‐rich diet, or a MED diet for 8 weeks on metabolite profiles, in 47 subjects at risk of the metabolic syndrome. A total of 162 serum metabolites are assessed before and after the intervention by using a targeted NMR platform. Fifty‐two metabolites are changed during the intervention (false discovery rate [FDR] p < 0.05). Both the MUFA and MED diet decrease exactly the same fractions of LDL, including particle number, lipid, phospholipid, and free cholesterol fraction (FDR p < 0.05). The MED diet additionally decreases the larger subclasses of very‐low‐density lipoprotein (VLDL), related VLDL fractions, VLDL‐triglycerides, and serum‐triglycerides (FDR p < 0.05).ConclusionThe findings clearly demonstrate that the MUFA component is responsible for reducing LDL subclasses and fractions, and therefore causes an antiatherogenic lipid profile. Interestingly, consumption of the other components in the MED diet show additional health effects.

Postprandial Activation of P53-Dependent DNA Repair Is Modified by Mediterranean Diet Supplemented With Coenzyme Q10 in Elderly Subjects

Alterations in the expression levels of genes and proteins involved in oxidative stress and DNA damage response underlie the phenotypic changes associated with aging. We have investigated whether the quality of dietary fat alters postprandial gene expression and protein levels involved in p53-dependent DNA repair and whether the supplementation with Coenzyme Q10 improves this situation in an elderly population. Twenty participants were randomized to receive three isocaloric diets each for 4 weeks: Mediterranean diet supplemented with Coenzyme Q10, Mediterranean diet, saturated fatty acid-rich diet. After a 12-hour fast, volunteers consumed a breakfast with a fat composition similar to that consumed in each of the diets. Gadd45a, Gadd45b, OGG1, APE-1/Ref-1, DNApolβ, and XPC gene expression and nuclear Gadd45a, APE-1/Ref-1, and DNApolβ protein levels were determined in peripheral blood mononuclear cells. Mediterranean diet and Mediterranean diet supplemented with Coenzyme Q10diets downregulated Gadd45a protein levels compared with the saturated fatty acid-rich diet. Moreover, Mediterranean diet supplemented with Coenzyme Q10diet evoked lower postprandial Gadd45a, Gadd45b, XPC, DNApolβ and OGG1 gene expression and lower APE-1/Ref-1 and DNApolβ protein levels than the saturated fatty acid-rich diet. Our results support a beneficial effect of Mediterranean diet and Mediterranean diet supplemented with Coenzyme Q10 on DNA damage as compared to the detrimental action of a saturated fatty acid-rich diet, which triggers the p53-dependent DNA repair machinery.

Endothelial Acyl-CoA Synthetase 1 Is Not Required for Inflammatory and Apoptotic Effects of a Saturated Fatty Acid-Rich Environment

Saturated fatty acids, such as palmitic and stearic acid, cause detrimental effects in endothelial cells and have been suggested to contribute to macrophage accumulation in adipose tissue and the vascular wall, in states of obesity and insulin resistance. Long-chain fatty acids are believed to require conversion into acyl-CoA derivatives to exert most of their detrimental effects, a reaction catalyzed by acyl-CoA synthetases (ACSLs). The objective of this study was to investigate the role of ACSL1, an ACSL isoform previously shown to mediate inflammatory effects in myeloid cells, in regulating endothelial cell responses to a saturated fatty acid-rich environment in vitro and in vivo. Saturated fatty acids caused increased inflammatory activation, endoplasmic reticulum stress, and apoptosis in mouse microvascular endothelial cells. Forced ACSL1 overexpression exacerbated the effects of saturated fatty acids on apoptosis and endoplasmic reticulum stress. However, endothelial ACSL1 deficiency did not protect against the effects of saturated fatty acids in vitro, nor did it protect insulin-resistant mice fed a saturated fatty acid-rich diet from macrophage adipose tissue accumulation or increased aortic adhesion molecule expression. Endothelial ACSL1 is not required for inflammatory and apoptotic effects of a saturated fatty acid-rich environment.

Abstract 19596: Endothelial Acyl-CoA Synthetase 1 is not Required for Saturated Fatty Acid- Mediated Inflammatory and Apoptotic Effects

Saturated fatty acids, such as palmitic (C16:0) and stearic acid (C18:0), cause detrimental effects in endothelial cells (ECs) that might contribute to macrophage accumulation in adipose tissue and the vascular wall in states of obesity and insulin resistance. Fatty acids require conversion into acyl-CoA derivatives to exert most biological effects, a reaction catalyzed by acyl-CoA synthetases (ACSL). We hypothesized that endothelial deficiency of ACSL1, an ACSL isoform mediating inflammatory effects in myeloid cells, would protect from detrimental effects of saturated fatty acids in vitro and saturated fat feeding in vivo. Mouse microvascular CD45-negative-CD31-positive endothelial cells (MMECs) were isolated from lungs or hearts by fluorescence activated cell sorting. In these cells and in bovine aortic ECs (BAECs), saturated fatty acids caused JNK activation, ER stress, and apoptosis, along with increased inflammatory activation, as measured by an increase in the release of the soluble adhesion molecules sICAM-1 (p&lt;0.01), and sVCAM-1 (p&lt;0.01), as well as release of the chemokine CCL2 (p&lt;0.05). In order to evaluate the role of endogenous ACSL1 in ECs, a conditional endothelial Acsl1-deficient mouse model was generated. Acsl1-deficient MMECs had significantly decreased beta-oxidation as measured by decreased acid soluble metabolite production (WT 393.1 ± 25.6, KO 270.5 ± 16.3 cpm/µg protein; p&lt;0.05). However, conditional endothelial ACSL1-deficiency did not protect against the inflammatory or apoptotic effects of saturated fatty acids in vitro, nor did it protect insulin resistant mice fed a saturated fatty acid-rich diet from epididymal adipose tissue accumulation of macrophages or increased aortic adhesion molecule expression. Conversely, forced Acsl1 overexpression in BAECs exacerbated the effects of saturated fatty acids on apoptosis and ER stress, in part through increased JNK activation. In conclusion, forced overexpression of Acsl1 can exacerbate some effects of saturated fatty acids; however, endogenous ACSL1 is not required for pro-inflammatory or pro-apoptotic responses of ECs to saturated fatty acids.

Diurnal feeding in young rats fed saturated fatty acid-rich diet

This study investigated eating pattern in weaning female Sprague-Dawley rats fed high-fat diets of varying fatty acid composition. Rats were randomly assigned to canola- or butter-based diets, and their eating pattern and body weight were assessed at early exposure (P1) and following 3 weeks (P2). In P2, a lower 24-h intake, smaller meal size, and shorter nocturnal meal duration were found in both dietary groups. In both groups, 24-h intakes were comparable throughout the experiment; however, butter-fed rats gained more weight. With canola feeding, P1 nocturnal intake was greater than diurnal intake, but intakes were comparable in P2. Butter-fed rats had similar diurnal and nocturnal intakes in P1; in P2, diurnal was greater than nocturnal intake. Canola-fed rats had similar diurnal and nocturnal meal size and eating rate, whereas butter-fed rats ate larger meals at a higher rate in the light than in the dark phase. The present work brings new knowledge about exposure to high-fat diets early in life and later development of obesity.

Postprandial antioxidant gene expression is modified by Mediterranean diet supplemented with coenzyme Q10 in elderly men and women

Postprandial oxidative stress is characterized by an increased susceptibility of the organism towards oxidative damage after consumption of a meal rich in lipids and/or carbohydrates. We have investigated whether the quality of dietary fat alters postprandial gene expression and protein levels involved in oxidative stress and whether the supplementation with coenzyme Q(10) (CoQ) improves this situation in an elderly population. Twenty participants were randomized to receive three isocaloric diets each for 4weeks: Mediterranean diet supplemented with CoQ (Med + CoQ diet), Mediterranean diet (Med diet), saturated fatty acid-rich diet (SFA diet). After 12-h fast, volunteers consumed a breakfast with a fat composition similar to that consumed in each of the diets. Nrf2, p22(phox) and p47(phox), superoxide dismutase 1 and 2 (SOD1 and SOD2), glutathione peroxidase 1 (GPx1), thiorredoxin reductase (TrxR) gene expression and Kelch-like ECH associating protein 1 (Keap-1) and citoplasmic and nuclear Nrf2 protein levels were determined. Med and Med + CoQ diets induced lower Nrf2, p22(phox), p47(phox), SOD1, SOD2 and TrxR gene expression and higher cytoplasmic Nrf2 and Keap-1 protein levels compared to the SFA diet. Moreover, Med + CoQ diet produced lower postprandial Nrf2 gene expression and lower nuclear Nrf2 protein levels compared to the other diets and lower GPx1 gene expression than the SFA diet. Our results support the antioxidant effect of a Med diet and that exogenous CoQ supplementation has a protective effects against free radical overgeneration through the lowering of postprandial oxidative stress modifying the postprandial antioxidant protein levels and reducing the postprandial expression of antioxidant genes in peripheral blood mononuclear cells.

Mediterranean Diet Supplemented With Coenzyme Q10 Modifies the Expression of Proinflammatory and Endoplasmic Reticulum Stress–Related Genes in Elderly Men and Women

We have investigated whether the quality of dietary fat and supplementation with coenzyme Q(10) (CoQ) modifies expression of genes related with inflammatory response and endoplasmic reticulum stress in elderly persons. Twenty participants received three diets for 4 weeks each: Mediterranean diet + CoQ (Med + CoQ), Mediterranean diet (Med), and saturated fatty acid-rich diet (SFA). After 12-hour fast, volunteers consumed a breakfast with a fat composition similar to that consumed in each of the diets. Med and Med + CoQ diets produced a lower fasting calreticulin, IL-1b, and JNK-1 gene expression; a lower postprandial p65, IKK-b, MMP-9, IL-1b, JNK-1, sXBP-1, and BiP/Grp78 gene expression; and a higher postprandial IkB-a gene expression compared with the SFA diet. Med + CoQ diet produced a lower postprandial decrease p65 and IKK-b gene expression compared with the other diets. Our results support the anti-inflammatory effect of Med diet and that exogenous CoQ supplementation in synergy with a Med diet modulates the inflammatory response and endoplasmic reticulum stress.

Mediterranean diet supplemented with coenzyme Q10 induces postprandial changes in p53 in response to oxidative DNA damage in elderly subjects

Coenzyme Q10 (CoQ) is a powerful antioxidant that reduces oxidative stress. We explored whether the quality of dietary fat alters postprandial oxidative DNA damage and whether supplementation with CoQ improves antioxidant capacity by modifying the activation/stabilization of p53 in elderly subjects. In this crossover study, 20 subjects were randomly assigned to receive three isocaloric diets during 4 weeks each: (1) Mediterranean diet (Med diet), (2) Mediterranean diet supplemented with CoQ (Med+CoQ diet), and (3) saturated fatty acid-rich diet (SFA diet). Levels of mRNAs were determined for p53, p21, p53R2, and mdm2. Protein levels of p53, phosphorylated p53 (Ser20), and monoubiquitinated p53 were also measured, both in cytoplasm and nucleus. The extent of DNA damage was measured as plasma 8-OHdG. SFA diet displayed higher postprandial 8-OHdG concentrations, p53 mRNA and monoubiquitinated p53, and lower postprandial Mdm2 mRNA levels compared with Med and Med+CoQ diets (p < 0.05). Moreover, Med+CoQ diet induced a postprandial decrease of cytoplasmatic p53, nuclear p-p53 (Ser20), and nuclear and cytoplasmatic monoubiquitinated p53 protein (p < 0.05). In conclusion, Med+CoQ diet improves oxidative DNA damage in elderly subjects and reduces processes of cellular oxidation. Our results suggest a starting point for the prevention of oxidative processes associated with aging.

Comment on the article “A saturated fatty acid–rich diet induces an obesity-linked proinflammatory gene expression profile in adipose tissue of subjects at risk of metabolic syndrome”

Comment on the article “A saturated fatty acid–rich diet induces an obesity-linked proinflammatory gene expression profile in adipose tissue of subjects at risk of metabolic syndrome”

Postprandial antioxidant effect of the Mediterranean diet supplemented with coenzyme Q10 in elderly men and women

Postprandial oxidative stress is characterized by an increased susceptibility of the organism towards oxidative damage after consumption of a meal rich in lipids and/or carbohydrates. We have investigated whether the quality of dietary fat alters postprandial cellular oxidative stress and whether the supplementation with coenzyme Q(10) (CoQ) lowers postprandial oxidative stress in an elderly population. In this randomized crossover study, 20 participants were assigned to receive three isocaloric diets for periods of 4 week each: (1) Mediterranean diet supplemented with CoQ (Med+CoQ diet), (2) Mediterranean diet (Med diet), and (3) saturated fatty acid-rich diet (SFA diet). After a 12-h fast, the volunteers consumed a breakfast with a fat composition similar to that consumed in each of the diets. CoQ, lipid peroxides (LPO), oxidized low-density lipoprotein (oxLDL), protein carbonyl (PC), total nitrite, nitrotyrosine plasma levels, catalase, superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities and ischemic reactive hyperaemia (IRH) were determined. Med diet produced a lower postprandial GPx activity and a lower decrease in total nitrite level compared to the SFA diet. Med and Med+CoQ diets induced a higher postprandial increase in IRH and a lower postprandial LPO, oxLDL, and nitrotyrosine plasma levels than the SFA diet. Moreover, the Med+CoQ diet produced a lower postprandial decrease in total nitrite and a greater decrease in PC levels compared to the other two diets and lower SOD, CAT, and GPx activities than the SFA diet.In conclusion, Med diet reduces postprandial oxidative stress by reducing processes of cellular oxidation and increases the action of the antioxidant system in elderly persons and the administration of CoQ further improves this redox balance.

A saturated fatty acid–rich diet induces an obesity-linked proinflammatory gene expression profile in adipose tissue of subjects at risk of metabolic syndrome

BackgroundChanges in dietary fat composition could lower the risk of developing metabolic syndrome. Adipose tissue is an interesting tissue in this respect because of its role in lipid metabolism and inflammation. ObjectiveOur objective was to investigate the effect of a saturated fatty acid (SFA)– and a monounsaturated fatty acid (MUFA)–rich diet on insulin sensitivity, serum lipids, and gene expression profiles of adipose tissue in subjects at risk of metabolic syndrome. DesignA parallel controlled-feeding trial was conducted in 20 abdominally overweight subjects. Subjects received an SFA diet or a MUFA diet for 8 wk. Plasma and subcutaneous adipose tissue samples were obtained, and insulin sensitivity was measured by using a hyperinsulinemic-euglycemic clamp. Adipose tissue samples underwent whole-genome microarray and histologic analysis. Plasma and adipose tissue fatty acid composition and concentrations of serum cholesterol and plasma cytokine were determined. ResultsConsumption of the SFA diet resulted in increased expression of genes involved in inflammation processes in adipose tissue, without changes in morphology or insulin sensitivity. The MUFA diet led to a more antiinflammatory gene expression profile, which was accompanied by a decrease in serum LDL-cholesterol concentrations and an increase in plasma and adipose tissue oleic acid content. ConclusionsConsumption of an SFA diet resulted in a proinflammatory “obesity-linked” gene expression profile, whereas consumption of a MUFA diet caused a more antiinflammatory profile. This suggests that replacement of dietary SFA with MUFA could prevent adipose tissue inflammation and may reduce the risk of inflammation-related diseases such as metabolic syndrome. This trial was registered at clinicaltrials.gov as NCT00405197.

Postprandial lipid metabolism

Atherogenic effects of postprandial lipoproteins are supported by many studies comparing patients with advanced clinical signs or early markers of cardiovascular disease with subjects without vascular disease. Postprandial lipoprotein abnormalities are more frequent in individuals with type 2 diabetes and other states of insulin resistance, which could be a major factor accounting for the higher rate of cardiovascular diseases observed in these conditions. In patients with type 2 diabetes multiple abnormalities of lipoproteins of both endogenous and exogenous origin are observed also in the presence of good blood glucose control and normal fasting triglyceridaemia, and a direct role of insulin resistance in the development of postprandial dyslipidaemia has been demonstrated. Clinical and experimental studies have demonstrated that a high fat consumption is associated with impaired insulin sensitivity and may worsen postprandial hypertriglyceridemia in individuals with type 2 diabetes and/or hyperlipidaemia. In addition to the amount of fat also the physical structure of the food in which fat is present is able to influence postprandial lipaemia. Data on the effects of dietary fatty acid (FA) modifications in humans are scarce. These studies have provided some evidence that dietary polyunsaturated FA, particularly those of the n-3 class, induce an attenuated postprandial lipaemic response as compared to saturated FA (SFA) and monounsaturated FA (MUFA); however, the data are often conflicting and their interpretation is, generally, controversial. Very little is known in patients with type 2 diabetes, in whom both insulin sensitivity and postprandial lipaemia are particularly relevant. In a medium term (3 weeks) study in type 2 diabetic patients, a MUFA rich diet did not modify insulin sensitivity as compared to the SFA rich diet. The MUFA diet induced a higher early peak of chylomicrons and a significantly lower postprandial response o f small VLDL after a standard test meal, rich in saturated fat. In conclusion, postprandial lipoprotein abnormalities are a frequent feature of type 2 diabetes and of other conditions clustering with insulin resistance. The total amount of fat, more than the specific type of fatty acid, seems to influence postprandial lipoproteins. Data are needed on long term interventions as well as on the interactions between dietary fat and other food components or physical structure. Keywords: postprandial lipoproteins; metabolism of dietary fat

High-Fat Feeding During Gestation and Nursing Period have Differential Effects on the Insulin Secretory Capacity in Offspring from Normal Wistar Rats

Restriction of protein or energy intake during gestation or early life is linked to developmental defects in the endocrine pancreas and insulin resistance. To study whether a saturated fatty acid-rich diet during gestation and/or after the weaning period may be detrimental to the insulin secretory capacity later in life. Female Wistar rats were fed diets rich in carbohydrate (CHO) or saturated fat (SAFA) during pregnancy. The male offspring were split into five subgroups: after birth group 1 (control) continued on CHO and group 3 on SAFA. Group 2 continued on the CHO diet during the nursing period but changed to SAFA post weaning. Group 4 continued on SAFA, but changed to CHO post weaning. For group 5 the offspring of mothers given a SAFA diet were changed to nursing mothers on a CHO diet immediately after birth, and continued on the same diet post weaning. After 14 wk, the islets of Langerhans were isolated for determination of insulin secretory capacity in static incubation and dynamic perifusion experiments. We found a negative correlation (Coef: -3.1, 95% CI: -6.1 to -0.0, p < 0.05) between a diet rich in saturated fat fed to mothers during gestation and a positive correlation (Coef: 4.4, 95% CI: 0.9 to 7.8, p = 0.01) between nursing mothers' diet and the capability to secrete insulin in the offspring. Our results indicate the importance of applying a nutrient-balanced diet during pregnancy and the nursing period on the later insulin secretory capacity in the offspring.

Low-fat and high–monounsaturated fatty acid diets decrease plasma cholesterol ester transfer protein concentrations in young, healthy, normolipemic men

Cholesterol ester transfer protein (CETP) mediates the transfer of cholesteryl esters from HDL to apolipoprotein (apo) B-containing lipoproteins. The possible atherogenic role of this protein is controversial. Diet may influence plasma CETP concentrations. The objective was to determine whether the changes in plasma lipids observed after consumption of 2 lipid-lowering diets are associated with changes in plasma CETP concentrations. : We studied 41 healthy, normolipidemic men over 3 consecutive 4-wk dietary periods: a saturated fatty acid-rich diet (SFA diet: 38% fat, 20% saturated fat), a National Cholesterol Education Program Step I diet (NCEP Step I diet: 28% fat, 10% saturated fat), and a monounsaturated fatty acid-rich diet (MUFA diet: 38% fat, 22% monounsaturated fat). Cholesterol content (27.5 mg/MJ) was kept constant during the 3 periods. Plasma concentrations of total, LDL, and HDL cholesterol; triacylglycerol; apo A-I and B; and CETP were measured at the end of each dietary period. Compared with the SFA diet, both lipid-lowering diets significantly decreased plasma total and LDL cholesterol, apo B, and CETP. Only the NCEP Step I diet lowered plasma HDL cholesterol. Positive, significant correlations were found between plasma CETP and total (r = 0.3868, P < 0.0001) and LDL (r = 0.4454, P < 0.0001) cholesterol and also between changes in CETP concentrations and those of total (r = 0.4543, P < 0.0001) and LDL (r = 0.4554, P < 0.0001) cholesterol. The isoenergetic substitution of a high-saturated fatty acid diet with an NCEP Step I or a high-monounsaturated fatty acid diet decreases plasma CETP concentrations.

Fecal Sterol Excretion in Rats Fed Diets Enriched in Linoleic, .ALPHA.-Linolenic, and Eicosapentaenoic Plus Docosahexaenoic Acid.

The effects of feeding rats diets enriched in linoleic, α-linolenic, and eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) on plasma and liver cholesterol as well as on fecal excretion of neutral sterols and bile acids were examined. Male Sprague-Dawley rats were divided into four groups (n=7) and were fed isocaloric, isocholesterolemic, nutritionally adequate diets containing 20% (w/w) fat for four weeks. The diets contained high amounts of either beef tallow, sunflower oil, linseed oil or fish oil to achieve diets rich in saturated fats, linoleic acid, α-linolenic, or EPA plus DHA respectively. Rat feces were collected during the last three days of the fourth week and blood and livers were obtained at the end of the feeding period. Fecal sterol excretion (neutral sterols plus bile acids) was significantly higher in rats fed the linoleic and the α-linolenic acid-rich diets compared to those fed the saturated fatty acid-rich diet. Higher sterol excretion rate in the linoleic acid diet group was found to be primarily due to higher excretion of plant sterols, whereas cholesterol excretion as such was rather lower than that with the saturated fatty acid diet. Higher sterol excretion rate following the feeding of the α-linolenic acid-rich diet was mainly due to higher excretion of bile acids, specifically lithocholic and β-muricholic acid. Feeding of the linoleic acid-rich diet had no significant effect on bile acid excretion. EPA plus DHA, at the levels fed, had no effect on serum and liver cholesterol or on fecal excretion of total neutral sterol or bile acids, but significantly increased coprostanol excretion compared with that in the other groups. These data suggest that dietary linoleic acid reduces cholesterol excretion, which may partly be responsible for cholesterol accumulation in the hepatic tissue whereas n-3 fatty acids of plant (α-linolenic acid) and marine (EPA/DHA) origin increase fecal cholesterol excretion via different mechanisms, i.e., by increased conversion of cholesterol into bile acids.

Effect of fatty acid-rich diets on thymocyte proliferation and thymus involution during growing

The effect of polyunsaturated and saturated fatty acid-rich diet on the proliferation response of T and B lymphocytes in vitro was investigated. Also, a mitotic index of thymocytes and of thymus epithelial reticular-like cells and thymic involution coefficient were examined in vivo. w-6 PUFA-rich diet enhanced the rate of T (eightfold) and B (fourfold) lymphocyte proliferation, whereas saturated fatty acids did not show an important effect. However, both fat-rich diets increased the mitotic index of thymocytes and thymus involution index in vivo. These findings suggest that fat-rich diets may accelerate thymus involution during growing, possibly aggravating the impairment of the immune function which usually occurs under this condition.

Omega-3 PUFA's reduce the vulnerability of the rat heart to ischaemic arrhythmia in the presence of a high intake of saturated animal fat

The effect of dietary lipids upon the development of cardiac arrhythmias has been studied in an animal model of Sudden Cardiac Death. Ischaemic arrhythmia in mature male rats was induced by occlusion of the coronary artery. After 44 weeks of feeding various lipid modified diets, it was demonstrated that complete substitution of omega-6 polyunsaturated fatty acids (PUFA's) for saturated animal fat produced great benefits in cardiac function; as the number of ventricular premature beats (VPB), and the incidence (%) and severity (duration in seconds) of both ventricular tachycardia (VT) and ventricular fibrillation (VF) were markedly reduced. However, when mixed diets containing additional saturated fat (SF) plus either sunflower seed oil (SSO) rich in omega-6 PUFA or fish oil (FO) containing omega-3 PUFA's were compared, it was apparent that the inclusion of a relatively small proportion of omega-3 PUFA's in the diet was of great benefit as no VF was recorded in this group, whereas a similar proportion of omega-6 PUFA added to a saturated fatty acid rich diet was without significant effect. As the mixed SF/PUFA diets were constructed to contain essentially similar proportions of both saturated and monounsaturated fatty acids, but with contrasting amounts of either omega-6 or omega-3 PUFA's, the benefits observed by the inclusion of omega-3 PUFA's in the diet were direct and not due to coincidental changes in other fatty acid components of the diets.