SFA-rich Diet Research Articles

Monounsaturated fatty acid antagonizes saturated fatty acid-induced cardiomyopathy via improving membrane fatty acid composition and endoplasmic reticulum stress

Abstract Background Obesity-induced lipotoxicity causes cardiac dysfunction in our modern lifestyle. Previously, we have shown that an increase in cardiomyocyte membrane saturated fatty acid (SFA)/ monounsaturated FA (MUFA) ratio mediates endoplasmic reticulum (ER) stress, which was implicated in the pathogenesis of SFA-induced cardiomyopathy. Furthermore, SFA supressed Sirt1/ stearoyl-CoA desaturase-1 (SCD1, converting enzyme from SFA to MUFA) signaling, which further worsened the membrane SFA/MUFA ratio. Purpose To evaluate the effectiveness of targeting membrane fatty acid composition by MUFA. Methods and results In wild-type mice, 16-weeks SFA-rich high lard diet feeding (HLD) caused activation of PPARα signaling and the accumulation of toxic lipid intermediates (diacylglycerol and ceramide) in the heart to the same extent as a MUFA-rich high olive oil diet feeding (HOD). However, only the HLD impaired Sirt1 activity, SCD1 expression, diastolic function (increased left ventricular end-diastolic pressure (LVEDP) and end-diastolic pressure-volume relationship (EDPVR)), and cardiac remodeling (hypertrophy and fibrosis). Lipidome analysis showed that HLD-induced diastolic dysfunction coincided with an increase in membrane SFA/MUFA ratio and ER stress induction. 8-weeks HOD after 8-weeks HLD (HOD switch) showed the same degree of obesity and PPARα activation with 16-weeks HLD. By contrast, HOD switched heart were less severe Sirt1/SCD1 signaling dysregulation, increased in membrane SFA/MUFA ratio, ER stress, and cardiomyopathy (hypertrophy, fibrosis, and diastolic dysfunction) compared to 16-weeks HLD. Moreover, in cardiomyocyte-specific Sirt1 knockout mice, HOD switched heart also showed less severe increase in membrane SFA/MUFA ratio, ER stress, and cardiomyopathy compared to 16-weeks HLD although decreased SCD1 expression was not changed. Conclusions We demonstrated that MUFA-rich diet counteracted SFA-induced Sirt1/SCD1 signaling dysregulation and prevented SFA-induced increase in membrane SFA/MUFA ratio. Hence, MUFA-rich diet antagonized SFA-induced ER stress and cardiomyopathy even if Sirt1 deactivated heart (e.g., aged heart). Targeting the cardiomyocyte membrane SFA/MUFA ratio by MUFA might have a new therapeutic potential for SFA-induced cardiomyopathy. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): JSPS KAKENHI

Impact of Dietary Fat on the Progression of Liver Fibrosis: Lessons from Animal and Cell Studies.

Previous studies have revealed that a high-fat diet is one of the key contributors to the progression of liver fibrosis, and increasing studies are devoted to analyzing the different influences of diverse fat sources on the progression of non-alcoholic steatohepatitis. When we treated three types of isocaloric diets that are rich in cholesterol, saturated fatty acid (SFA) and trans fatty acid (TFA) with hepatitis C virus core gene transgenic mice that spontaneously developed hepatic steatosis without apparent fibrosis, TFA and cholesterol-rich diet, but not SFA-rich diet, displayed distinct hepatic fibrosis. This review summarizes the recent advances in animal and cell studies regarding the effects of these three types of fat on liver fibrogenesis.

The C. elegans PAQR-2 and IGLR-2 membrane homeostasis proteins are uniquely essential for tolerating dietary saturated fats

How cells maintain vital membrane lipid homeostasis while obtaining most of their constituent fatty acids from a varied diet remains largely unknown. Here, we report the first whole-organism (Caenorhabditis elegans) forward genetic screen to identify genes essential for tolerance to dietary saturated fatty acids (SFAs). We found that only the PAQR-2/IGLR-2 pathway, homologous to the human adiponectin receptor 2 (AdipoR2) pathway, is uniquely essential to prevent SFA-mediated toxicity. When provided a SFA-rich diet, worms lacking either protein accumulate an excess of SFAs in their membrane phospholipids, which is accompanied by membrane rigidification. Additionally, we used fluorescence resonance energy transfer (FRET) to show that the interaction between PAQR-2 and IGLR-2 is regulated by membrane fluidity, suggesting a mechanism by which this protein complex senses membrane properties. We also created versions of PAQR-2 that lacked parts of the cytoplasmic N-terminal domain and showed that these were still functional, though still dependent on the interaction with IGLR-2. We conclude that membrane homeostasis via the PAQR-2/IGLR-2 fluidity sensor is the only pathway specifically essential for the non-toxic uptake of dietary SFAs in C. elegans.

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.

Replacement of dietary saturated fat with unsaturated fats increases numbers of circulating endothelial progenitor cells and decreases numbers of microparticles: findings from the randomized, controlled Dietary Intervention and VAScular function (DIVAS) study

Endothelial progenitor cells (EPCs) and microparticles are emerging as novel markers of cardiovascular disease (CVD) risk, which could potentially be modified by dietary fat. We have previously shown that replacing dietary saturated fatty acids (SFAs) with monounsaturated or n-6 (ω-6) polyunsaturated fatty acids (MUFAs or PUFAs, respectively) improved lipid biomarkers, blood pressure, and markers of endothelial activation, but their effects on circulating EPCs and microparticles are unclear. The Dietary Intervention and VAScular function (DIVAS) Study investigated the replacement of 9.5-9.6% of total energy (%TE) contributed by SFAs with MUFAs or n-6 PUFAs for 16 wk on EPC and microparticle numbers in United Kingdom adults with moderate CVD risk. In this randomized, controlled, single-blind, parallel-group dietary intervention, men and women aged 21-60 y (n=190) with moderate CVD risk (≥50% above the population mean) consumed 1 of three 16-wk isoenergetic diets. Target compositions for total fat, SFAs, MUFAs, and n-6 PUFAs (%TE) were as follows: SFA-rich diet (36:17:11:4; n=64), MUFA-rich diet (36:9:19:4; n=62), and n-6 PUFA-rich diet (36:9:13:10; n=66). Circulating EPC, endothelial microparticle (EMP), and platelet microparticle (PMP) numbers were analyzed by flow cytometry. Dietary intake, vascular function, and other cardiometabolic risk factors were determined at baseline. Relative to the SFA-rich diet, MUFA- and n-6 PUFA-rich diets decreased EMP (-47.3%, -44.9%) respectively and PMP (-36.8%, -39.1%) numbers (overall diet effects, P<0.01). The MUFA-rich diet increased EPC numbers (+28.4%; P=0.023). Additional analyses that used stepwise regression models identified the augmentation index (measuring arterial stiffness determined by pulse-wave analysis) as an independent predictor of baseline EPC and microparticle numbers. Replacement of 9.5-9.6%TE dietary SFAs with MUFAs increased EPC numbers, and replacement with either MUFAs or n-6 PUFAs decreased microparticle numbers, suggesting beneficial effects on endothelial repair and maintenance. Further studies are warranted to determine the mechanisms underlying the favorable effects on EPC and microparticle numbers after SFA replacement. This trial was registered at www.clinicaltrials.gov as NCT01478958.

Diet and ambient temperature interact to shape plasma fatty acid composition, basal metabolic rate, and oxidative stress in great tits

Diet and ambient temperature affect animal physiology, survival and reproductive success. However, knowledge of how these environmental factors interact to shape physiological processes and life-history traits of birds and other animals is largely lacking. By exposing adult great tits (Parus major) to two contrasting diets (saturated or unsaturated fatty acids; SFAs and UFAs, respectively) and ambient temperatures (3°C versus 20°C) that the birds encounter in nature, we investigated the effects of these two factors on several physiological parameters. Our results show that diet and ambient temperature interact to affect the composition of plasma fatty acids, basal metabolic rate (BMR) and oxidative stress, which are thought to affect the life-history and survival of individuals. Specifically, birds provided the SFA-rich diet had higher mass-specific BMR and oxidative stress (levels of lipid peroxidation) after exposure to low compared with high ambient temperature, whereas the opposite pattern was evident for birds with a UFA-rich diet. Surprisingly, birds on the SFA diet had higher relative levels of monounsaturated fatty acids compared with the UFA-fed birds at low ambient temperature, whereas the opposite, and expected, pattern was found at the high temperature. Although the present study focuses on the physiological implications of the diet×temperature interaction, our results might also be important for the leading theories of ageing, which currently do not take interactions between environmental factors into account. In addition, the present results are important for wildlife management, especially with regards to anthropogenic feeding of wild animals across variable and changing climatic conditions.

Endotoxemia is modulated by quantity and quality of dietary fat in older adults.

Aging is an important determinant of the rate of atherosclerosis development, mainly through low-grade inflammation. Diet, and particularly its fat content, modulates the inflammatory response in fasting and postprandial states. We aimed to study the effects of dietary fat on endotoxemia in healthy older adults. Twenty healthy older adults were randomized to three diets, lasting three-weeks each, using a crossover design: 1. A Mediterranean diet enriched in MUFA with virgin olive oil. 2. An SFA-rich diet. 3. A low-fat high-carbohydrate diet enriched in n-3 PUFA (α-linolenic acid of plant origin) (CHO-PUFA diet). At the end of each period, after a 12-h fast, the subjects received a meal with a composition similar to the dietary period just completed. We determined the fasting and the postprandial plasma levels of lipopolysaccharide (LPS) and LPS-binding protein (LBP). In the fasting state, we observed lower LPS plasma levels after the consumption of the CHO-PUFA diet (P=0.046) in comparison with the consumption of the Med and SFA-rich diets. In the postprandial measurements, we observed a statistically significant increase in plasma levels of LPS (P=0.044) and a decrease in LBP (P=0.003) after the intake of the CHO-PUFA meal, whereas no postprandial changes were observed after the ingestion of the Med and SFA-rich meals. Our results, together with those obtained in a previous study, support the concept that the consumption of the Med Diet, in contrast to a low-fat PUFA diet, constitutes a more suitable dietary lifestyle for preventing the development of atherosclerosis in a population at risk, such as older adults.

Corn oil versus lard: Metabolic effects of omega-3 fatty acids in mice fed obesogenic diets with different fatty acid composition.

Mixed results have been obtained regarding the level of insulin resistance induced by high-fat diets rich in saturated fatty acids (SFA) when compared to those enriched by polyunsaturated fatty acids (PUFA), and how metabolic effects of marine PUFA of n-3 series, i.e. docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), depend on dietary lipid background. Here we compared two high-fat diets, in which the major lipid constituent was based either on SFA in the form of pork lard (LHF diet) or PUFA of n-6 series (Omega-6) as corn oil (cHF diet). Both cHF and LHF parental diets were also supplemented with EPA+DHA (∼30g/kg diet) to produce cHF+F and LHF+F diet, respectively. Male C57BL/6N mice were fed the experimental diets for 8 weeks. Insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamps in mice fed LHF and cHF diets, and then metabolic effects of cHF+F and LHF+F diets were assessed focusing on the liver and epididymal white adipose tissue (eWAT). Both LHF and cHF induced comparable weight gain and the level of insulin resistance, however LHF-fed mice showed increased hepatic steatosis associated with elevated activity of stearoyl-CoA desaturase-1 (SCD1), and lower plasma triacylglycerol levels when compared to cHF. Despite lowering hepatic SCD1 activity, which was concomitant with reduced hepatic steatosis reaching the level observed in cHF+F mice, LHF+F did not decrease adiposity and the weight of eWAT, and rather further impaired insulin sensitivity relative to cHF+F, that tended to improve it. In conclusion, high-fat diets containing as much as ∼35 weight% as lipids induce similar weight gain and impairment of insulin sensitivity irrespective whether they are based on SFA or Omega-6. Although the SFA-rich diet containing EPA+DHA efficiently reduced hepatic steatosis, it did so without a corresponding improvement in insulin sensitivity and in the absence of effect on adiposity.

Erratum to: Feeding and digestive responses to fatty acid intake in two South American passerines with different food habits

Specific fatty acids (FA) such as unsaturated (UFA) and saturated (SFA) fatty acids contained in foods are key factors in the nutritional ecology of birds. By means of a field and experimental approach, we evaluated the effect of diet on the activity of three esterases involved in FA hydrolysis; carboxylesterase (CE: 4-NPA-CE and a-NA-CE) and butyrylcholinesterase, in two South American passerines: the omnivorous rufous-collared sparrow (Zonotrichia capensis) and the granivorous common diuca-finch (Diuca diuca). The activity of the three esterases was measured in the intestines of freshly caught individuals over two distinct seasons and also after a chronic intake of a UFA-rich or SFA-rich diet in the laboratory. In turn, we assessed the feeding responses of the birds choosing amongst diets contrasting in the kind of specific FA (UFA- vs. SFA-treated diets). During summer, field CE activities (4-NPA-CE and a-NA-CE) in the small intestine were higher in the rufous-collared sparrow (25.3 ± 3.3 and 81.4 ± 10.8 µmol min−1 g tissue−1, respectively) than in the common diuca-finch (10.0 ± 3.0 and 33.9 ± 13.1 µmol min−1 g tissue−1, respectively). Two hour feeding trial test indicated that both species exhibited a clear preference for UFA-treated diets. On average, the rufous-collared sparrow consumed 0.46 g 2 h−1 of UFA-rich diets and 0.12 g 2 h−1 of SFA-rich diets. In turn, the consumption pattern of the common diuca-finch averaged 0.73 and 0.16 g 2 h−1 for UFA-rich and SFA-rich diets, respectively. After a month of dietary acclimation to UFA-rich and SFA-rich diets, both species maintained body mass irrespective of the dietary regime. Additionally, the intestinal 4-NPA-CE activity exhibited by birds fed on a UFA-rich or SFA-rich diet was higher in the rufous-collared sparrow (39.0 ± 5.3 and 44.2 ± 7.3 µmol min−1 g tissue−1, respectively) than in the common diuca-finch (13.3 ± 1.9 and 11.2 ± 1.4 µmol min−1 g tissue−1, respectively). Finally, the intestinal a-NA-CE activity exhibited by the rufous-collared sparrow was about two times higher when consuming an UFA-rich diet. Our results suggest that the rufus-collared sparrow exhibits a greater capacity for intestinal FA hydrolysis, which would allow it to better deal with fats from different sources.

Development of a Food-Exchange Model to Replace Saturated Fat wth MUFAs and n–6 PUFAs in Adults at Moderate Cardiovascular Risk

The recommendation to reduce saturated fatty acid (SFA) consumption to ≤10% of total energy (%TE) is a key public health target aimed at lowering cardiovascular disease (CVD) risk. Replacement of SFA with unsaturated fats may provide greater benefit than replacement with carbohydrates, yet the optimal type of fat is unclear. The aim of the DIVAS (Dietary Intervention and Vascular Function) study was to develop a flexible food-exchange model to investigate the effects of substituting SFAs with monounsaturated fatty acids (MUFAs) or n–6 (ω-6) polyunsaturated fatty acids (PUFAs) on CVD risk factors. In this parallel study, UK adults aged 21–60 y with moderate CVD risk (50% greater than the population mean) were identified using a risk assessment tool (n = 195; 56% females). Three 16-wk isoenergetic diets of specific fatty acid (FA) composition (%TE SFA:%TE MUFA:%TE n–6 PUFA) were designed using spreads, oils, dairy products, and snacks as follows: 1) SFA-rich diet (17:11:4; n = 65); 2) MUFA-rich diet (9:19:4; n = 64); and 3) n–6 PUFA-rich diet (9:13:10; n = 66). Each diet provided 36%TE total fat. Dietary targets were broadly met for all intervention groups, reaching 17.6 ± 0.4%TE SFA, 18.5 ± 0.3%TE MUFA, and 10.4 ± 0.3%TE n–6 PUFA in the respective diets, with significant overall diet effects for the changes in SFAs, MUFAs, and n–6 PUFAs between groups (P < 0.001). There were no differences in the changes of total fat, protein, carbohydrate, and alcohol intake or anthropometric measures between groups. Plasma phospholipid FA composition showed changes from baseline in the proportions of total SFAs, MUFAs, and n–6 PUFAs for each diet group, with the changes in SFAs and MUFAs differing between the groups (P < 0.001). In conclusion, successful implementation of the food-exchange model broadly achieved the dietary target intakes for the exchange of SFAs with MUFAs or n–6 PUFAs with minimal disruption to the overall diet in a free-living population. This trial was registered at clinicaltrials.gov>as NCT01478958.

Postprandial oxidative stress is modulated by dietary fat in adipose tissue from elderly people

We have investigated whether dietary fat modifies the postprandial oxidative stress in adipose tissue of elderly people. Twenty participants received three diets for 4weeks each: SFA-rich diet, Mediterranean (Med) diet enriched in MUFA with virgin olive oil, and a low-fat, high-carbohydrate diet enriched in n-3 PUFA (α-linolenic acid from plant origin) (CHO-PUFA diet). After 12h of fasting, volunteers received a breakfast reflecting the fatty acid composition of the diet ingested in the preceding dietary period. Med diet induced higher postprandial SOD2 and TrxR mRNA levels, and CHO-PUFA diet induced higher GPx1 and TrxR mRNA levels compared with SFA-rich diet. Med and CHO-PUFA breakfasts induced a postprandial increase in plasma reduced glutathione (GSH), and a greater postprandial GSH/oxidized glutathione ratio compared to the SFA-rich diet. Our study suggests that the consumption of Med and CHO-PUFA diets may reduce postprandial oxidative stress compared to an SFA-rich diet, which may be due to higher antioxidant enzymes gene expression in adipose tissue.

Restoration of dietary-fat induced blood–brain barrier dysfunction by anti-inflammatory lipid-modulating agents

BackgroundSeveral studies have identified use of non-steroidal-anti-inflammatory drugs and statins for prevention of dementia, but their efficacy in slowing progression is not well understood. Cerebrovascular disturbances are common pathological feature of Alzheimer’s disease. We previously reported chronic ingestion of saturated fatty acids (SFA) compromises blood–brain barrier (BBB) integrity resulting in cerebral extravasation of plasma proteins and inflammation. However, the SFA-induced parenchymal accumulation of plasma proteins could be prevented by co-administration of some cholesterol lowering agents. Restoration of BBB dysfunction is clinically relevant, so the purpose of this study was to explore lipid-lowering agents could reverse BBB disturbances induced by chronic ingestion of SFA’s.MethodsWild-type mice were fed an SFA diet for 12 weeks to induce BBB dysfunction, and then randomised to receive atorvastatin, pravastatin or ibuprofen in combination with the SFA-rich diet for 2 or 8 weeks. Abundance of plasma-derived immunoglobulin-G (IgG) and amyloid-β enriched apolipoprotein (apo)-B lipoproteins within brain parenchyme were quantified utilising immunofluorescence microscopy.ResultsAtorvastatin treatment for 2 and 8 weeks restored BBB integrity, indicated by a substantial reduction of IgG and apo B, particularly within the hippocampus. Pravastatin, a water-soluble statin was less effective than atorvastatin (lipid-soluble). Statin effects were independent of changes in plasma lipid homeostasis. Ibuprofen, a lipid-soluble cyclooxygenase inhibitor attenuated cerebral accumulation of IgG and apo B as effectively as atorvastatin. Our findings are consistent with the drug effects being independent of plasma lipid homeostasis.ConclusionOur findings suggest that BBB dysfunction induced by chronic ingestion of SFA is reversible with timely introduction and sustained treatment with agents that suppress inflammation.

High‐fat from butter and sesame oils based diet have almost same effects on post energy expenditure (PEE) and satiety in healthy adults

The objective of this study was to compare the thermic effect of butter(SFA‐rich) and sesame oil(PUFA‐rich) based diet on PEE. Subjects were eight healthy university students aged 19–22 years. The meals were two isocaloric diet which consist of 50, 40, and 10% of fat, carbohydrate, and protein content, respectively. Energy expenditure was measured by indirect calorimetry and satiety (hunger, appetite, and prospective food consumption and fullness) was assessed by Visual Analogue Scales at preprandial and every 30 min over 5 hours after meal consumption. PEE of sesame oil diet increased more rapidly (peak at 90‐min) than butter diet (peak at 150‐min). However, PEE of butter diet decreased relatively faster after peak time. Total thermogenesis of butter(30.8 kcal/5h) was lower than that of sesame oil(34.4 kcal/5h ), but not significantly different. 6.5% of butter and 7.3% of sesame oil diet were contributed as thermic effect for those dietˈs digestion and absorption. There were no significant differences in thermic effects and satiety values between SFA rich diet and PUFA rich diet. Thus, number of double bond in fatty acid does not influence on energy expenditure.This research was supported by Basic Science Research Program, National Research Foundation of Korea funded by the Ministry of Education, Science and Technology.

Gut bacteria profiles of Mus musculus at the phylum and family levels are influenced by saturation of dietary fatty acids

BackgroundMammalian gut microbiota have been implicated in a variety of functions including the breakdown of ingested nutrients, the regulation of energy intake and storage, the control of immune system development and activity, and the synthesis of novel chemicals. Previous studies have shown that feeding mammalian hosts a high-fat diet shifts gut bacteria at the phylum level to reduce the ratio of Bacteroidetes-to-Firmicutes, while feeding hosts a fat-restricted diet increases this ratio. However, few studies have investigated the differential effects of fatty acid type on gut bacterial profile. MethodsOver a 14-week period, Mus musculus were fed a diet rich in omega-3 polyunsaturated fatty acids (n-3 PUFAs), omega-6 polyunsaturated fatty acids (n-6 PUFAs), or saturated fatty acids (SFAs). Fecal pellets were collected before and after the treatment period from 12 randomly selected mice (4 per treatment group). Bacterial DNA was extracted from the pellets and characterized by analysis of the hypervariable V3 region of the 16S rRNA. Nominal logistic regression models were used to assess shifts in microbial profile at the phylum and family levels in response to diet. ResultsA significant decrease in the proportion of phylum Bacteroidetes species was observed for mice fed any of the three diets over time. However, the SFA-rich diet group showed a significantly greater decrease in Bacteroidetes proportion (−28%) than did either the n-3 PUFA group (−10%) or the n-6 PUFA group (−12%). At the family level, a significant decrease in proportion of Porphyromonadaceae was observed for mice fed the n-6 PUFA-rich diet, and a significant decrease in proportion of Lachnospiraceae was observed for mice fed the SFA-rich diet. There was no significant effect of diet type on body mass change. ConclusionOur results indicate that SFAs have stronger effects than PUFAs in shifting gut microbiota profiles toward those typical of obese individuals, and that dietary fatty acid saturation influences shifts in gut microbiota independently of changes in body mass.

Effect of substituting saturated with monounsaturated fatty acids on serum visfatin levels and insulin resistance in overweight women: A randomized cross-over clinical trial

Objective: This study aimed to determine the effects of a monounsaturated fatty acids (MUFA)-rich diet on serum visfatin, interleukin-6 and insulin levels among overweight women. Design: In this randomized cross-over clinical trial, 17 premenopausal overweight women were included. Participants were randomly assigned to consume either a hypocaloric, saturated fatty acids (SFA)-rich diet (16% SFA and 8% MUFA) or a hypocaloric, MUFA-rich diet (16% MUFA and 8% SFA) for 12 weeks crossing over after a 2-week washout period. Percentages of energy from other macronutrients were similar between the two diets. Biochemical and anthropometric assessments were done at the first and at the end of each period. Statistical analyses were done using paired t-test. In all statistical analysis, p < 0.05 was considered as significant. Results: The participant's mean body mass index was 27.6 kg/m2. Mean percentages of MUFA intake were 13% during MUFA-rich diet and 7% during SFA-rich diet. The corresponding values for SFA intake were 8.5% and 14%, respectively. We failed to find any significant differences between two intervention diets in terms of their effect on the serum levels of IL-6, visfatin and insulin. However, serum visfatin and IL-6 levels increased during the SFA-rich diet (0.4 ± 0.4 ng/ml and 0.19 ± 0.3 pg/ml, respectively) and decreased during the MUFA-rich diet ( − 0.7 ± 0.5 ng/ml and − 0.17 ± 0.3 pg/ml, respectively). In spite of a slight reduction in both periods, changes in serum insulin levels did not reach significant levels comparing the two periods. Conclusions: Our findings did not support any significant effect of a MUFA-rich intake on serum IL-6 and insulin levels as compared with a SFA-rich diet; however, it has the potential to favourably affect serum visfatin levels.

Expression of proinflammatory, proatherogenic genes is reduced by the Mediterranean diet in elderly people

Ageing is an important determinant of atherosclerosis development rate, mainly by the creation of a chronic low-grade inflammation. Diet, and particularly its fat content, modulates the inflammatory response in the fasting and postprandial states. Our aim was to study the effects of dietary fat on the expression of genes related to inflammation (NF-κB, monocyte chemoattractant protein 1 (MCP-1), TNF-α and IL-6) and plaque stability (matrix metalloproteinase 9, MMP-9) during the postprandial state of twenty healthy, elderly people who followed three diets for 3 weeks each: (1) Mediterranean diet (Med Diet) enriched in MUFA with virgin olive oil; (2) SFA-rich diet; and (3) low-fat, high-carbohydrate diet enriched in n-3 PUFA (CHO-PUFA diet) by a randomised crossover design. At the end of each period, after a 12-h fast, the subjects received a breakfast with a composition similar to the one when the dietary period ended. In the fasting state, the Med Diet consumption induced a lower gene expression of the p65 subunit of NF-κB compared with the SFA-rich diet (P=0·019). The ingestion of the Med Diet induced a lower gene postprandial expression of p65 (P=0·033), MCP-1 (P=0·0229) and MMP-9 (P=0·041) compared with the SFA-rich diet, and a lower gene postprandial expression of p65 (P=0·027) and TNF-α (P=0·047) compared with the CHO-PUFA diet. Direct plasma quantification mostly reproduced the findings. Our data suggest that consumption of a Med Diet reduces the postprandial inflammatory response in mononuclear cells compared with the SFA-rich and CHO-PUFA diets in elderly people. These findings may be partly responsible for the lower CVD risk found in populations with a high adherence to the Med Diet.

Dietary Fatty Acids Affect the Immune System in Male Mice Sensitized to Ovalbumin or Vaccinated with Influenza ,

PUFA are precursor molecules for eicosanoids such as leukotrienes and prostaglandins and may influence immune function through other mechanisms involving membranes, cell signaling, and gene expression. Immune-modulating properties of diets containing different oils [sunflower oil, rich in linoleic acid; linseed oil, rich in a-linolenic acid; salmon oil, rich in marine (n-3) PUFA; and beef tallow, rich in SFA] were investigated in an influenza-vaccination model, in which the delayed-type hypersensitivity (DTH) response was studied in C57BL/6 mice, and an ovalbumin (OVA)-sensitization model for experimental allergy in BALB/c mice. Six-week-old mice were fed the different diets for 7 wk. The first vaccination or OVA sensitization was given 2 wk after the start of the dietary intervention. In the mice vaccinated with influenza, the DTH response to the vaccine was significantly higher in mice fed the marine (n-3) PUFA diet compared to all other groups, indicating that these PUFA promote a T helper-1 response. In the OVA-sensitized mice, those fed the marine (n-3) PUFA diet had a less severe acute allergic skin response (ASR), suggesting that (n-3) PUFA lessen the T helper-2 response. Mice fed the SFA-rich diet had the most severe ASR, indicating that a diet with high levels of SFA may contribute to increased severity of allergic symptoms. Whereas significant differences in in vivo immune responses were measured, in vitro responses did not differ among the dietary groups. In conclusion, using 2 different models of immune responses demonstrates potential benefits from marine (n-3) PUFA.

Hepatic lipid metabolism response to dietary fatty acids is differently modulated by PPARα in male and female mice

In human beings, women are at lower risk of cardiovascular diseases, and respond differently from men to dietary fatty acids. The aim of the present study was to investigate (i) the influence of gender on the response of lipid metabolism to dietary n-3 PUFA, and (ii) the contribution of PPARalpha to this response. Male and female mice, wild-type (WT) and PPARalpha-null (KO), were fed on diets rich in either saturated FA (SFA) or 18:3 n-3 (ALA). Lipid composition, mRNA levels and certain activities of key enzymes and major transcription factors were determined in the liver. WT mice were slightly affected by dietary FA. However, in WT female mice, but not in males, mRNA levels of PPARalpha-dependent genes (L-FABP, ACO) were higher in the mice fed on the ALA-rich diet. When compared to WT mice, KO female mice exhibited a decreased lipogenesis capacity (40% lower FAS, ACC, and SREBP-1c mRNA level), whereas KO males showed a decrease in peroxisomal beta-oxidation (activity and expression of ACO reduced by 20 and 40%, respectively). When compared to SFA-fed KO mice, steatosis was twice lower in KO mice fed on ALA, despite the absence of dietary effect on plasma TG, CPT1 and ACO activities, or ACC and FAS expression. Besides, in mice on the SFA diet, steatosis was alleviated in females, and CPT1 expression was up-regulated to a higher extent in females than in males (2.7- and 3.6-fold, respectively, as compared to the corresponding WT groups). Our data suggests estrogen to modulate the regulation of hepatic lipid metabolic pathway by dietary fatty acids. Besides, PPARalpha invalidation resulted in unexpected regulations by ALA of its known targets and was compensated partly in females, which was therefore less sensitive to the detrimental effects of a SFA-rich diet.

The effect of the plasma n-3/n-6 polyunsaturated fatty acid ratio on the dietary LDL phenotype transformation – Insights from the LIPGENE study

LDL phenotype B is associated with obesity, insulin resistance, hypertriglyceridemia and oxidative stress. The effect of plasma n-3/n-6 PUFA ratio on LDL phenotype transformation was investigated. Patients with metabolic syndrome (n=99) received one of four isocaloric diets: (A) High-fat (38% energy) SFA-rich diet (HSFA); (B) High-fat (38% energy), MUFA-rich diet (HMUFA); (C), low-fat (LF) (28% energy), high-complex carbohydrate diet with 1.24g/d oleic sunflower oil (LFHCC) and (D): low-fat (28% energy), high-complex carbohydrate diet, with 1.24g/d LC n-3 PUFA (LFHCC n-3) for 12 weeks. Analysis of plasma lipid profile and LDL phenotype was done pre- and post-interventions. Post-dietary change of LDL density was a main effect observed in all groups. LFHCC n-3 and HFMUFA diets resulted in favorable alteration of LDL phenotype from B to A and decreased LDL density. In contrast, increased LDL density was observed in HSFA and LFHCC groups. The plasma pre-n3/n6 PUFA, Apo E change and pre-Apo CIII/CII ratios explained in 65% the post-dietary change of LDL density in diet LFHCC n-3 consumers. Study demonstrates efficacy of dietary n-3 PUFA to modify pro-atherogenic to less atherogenic LDL phenotype in patients with metabolic syndrome. Study identifier at ClinicalTrials.gov was NCT00429195.

High fat diets increase TCR nano‐scale clustering

High fat diets have immunomodulatory effects on CD4+ T cell frequency, activation, and signaling. However, the mechanisms by which high fat diets modify T cell function remains to be elucidated. One emerging viewpoint is that dietary fatty acids change the plasma membrane's biophysical organization on a nano‐scale, which in turn disrupts T cell receptor (TCR)/co‐receptor distribution and function. In the present study, we tested if high fat diets enriched in either saturated or monounsaturated fatty acids could modify TCR nano‐scale clustering of naïve CD4+ T cells using a new method of quantum dot imaging and k‐space analysis. CD4 transgenic B10.BR mice were fed for 2 weeks a normal diet (5% fat by weight) or high fat diets (20% fat by weight) enriched in saturated (SFA) or monounsaturated (MUFA) fatty acids. Although both high fat diets increased TCR clustering, the SFA‐rich diet had the greatest effect. Splenic CD4+ T cells increased TCR nano‐scale clustering by ~50% suggesting that a SFA‐rich diet can alter the threshold for T cell activation. Our findings are consistent with our recent in vitro studies with SFAs on antigen presenting cells to show that changes in plasma membrane structure can significantly modify lymphocyte function. We suggest that high fat diets can modify the biophysical organization of the TCR, which may explain changes in T cell function of obese individuals.