Dietary Saturated Fatty Acids Research Articles

Dietary Saturated Fatty Acids Modulate Pain Behaviour in Trauma-Induced Osteoarthritis in Rats.

Osteoarthritis (OA) is a degenerative condition of joints, causing pain and swelling, and can be caused or worsened by trauma and obesity. The objectives of this study were to determine whether pain behaviour and progression of OA were increased in rats with trauma-induced OA fed dietary saturated fatty acids (SFA). Male Wistar rats were fed either a corn starch diet (C) or high-carbohydrate high-fat diet (H) with either 20% beef tallow or SFA (lauric (HLA), myristic (HMA), palmitic (HPA) or stearic (HSA) acids) for 16 weeks prior to and 8 weeks after excision of the medial meniscus of right knee joint to initiate OA when pain behaviour, glial activity, progression of knee OA, inflammatory mediators and signs of metabolic syndrome were assessed. Rats fed beef tallow, palmitic or stearic acids showed increased pain symptoms characterised by decreased hind paw/limb withdrawal thresholds and grip strengths and increased spinal astrogliosis and microgliosis compared to rats fed lauric or myristic acids. However, the severity of OA joint damage was unchanged by these dietary manipulations. We conclude that pain symptoms of trauma-induced OA in rats worsen with increased dietary beef tallow or palmitic or stearic acids, but improve with lauric or myristic acids, despite unchanged OA cartilage damage.

Association between saturated fatty acid intake and depressive symptoms in midlife women: A prospective study

BackgroundThis prospective investigation examined relations between baseline dietary saturated fatty acid (SFA) intake of women at midlife and prevalence of depressive symptoms 4 years later. MethodsWomen enrolled in the Study of Women's Health Across the Nation (SWAN) had measures of CES-D depression scores 4 years later and SFA intake at baseline. Logistic regression models were used to study prospective associations between SFA intake and depressive symptoms. ResultsA total of 2400 women aged 42–52 years were included in the present study. The ORs of depressive symptoms in model 1 adjustment for baseline CES-D score indicated that baseline SFA intake was positively associated with depressive symptoms. After additional adjustment for age, race/ethnicity, education, financial strain, physical activity, smoking currently, BMI, menopausal status, VMS, chronic stress and use of antidepressant in model 2, the results were similar to those of the model 1. This association remained statistically significant and changed little when additional controlling for SHBG and FSH in fully adjusted model 3. The fully adjusted OR of depressive symptoms in model 3 was 2.423 (1.142–5.143) in quartile 4 (the highest) versus quartile 1 (the lowest) of the baseline SFA intake. LimitationsAssessment of depression and SFA intake was based on a self-report scale. ConclusionsBaseline SFA intake is a predictor for depressive symptoms assessed 4 years later in midlife women. This underlines the importance of targeting SFA intake in the prevention of major depression in midlife women.

Apparent digestibility of proximate nutrients, energy and fatty acids in nutritionally-balanced diets with partial or complete replacement of dietary fish oil with microbial oil from a novel Schizochytrium sp. (T18) by juvenile Atlantic salmon (Salmo salar L.)

Oils derived from thraustochytrid microorganisms, particularly Schizochytrium sp., are rapidly gaining attention as sustainable feedstocks to replace conventional edible oils for many industrial applications. A novel strain of Schizochytrium sp. (T18) has shown rapid growth under optimized heterotrophic cultivation, efficiently using inexpensive carbon and nitrogen feedstocks and capable of producing a high docosahexaenoic acid (DHA)-rich oil. This is the first study directed towards its nutritional evaluation as a potential feed resource for salmonid aquaculture. The study examined the effects of partial or complete replacement of dietary marine fish oil with Schizochytrium sp. (T18) microbial oil on apparent digestibility (AD) of dietary proximate nutrients, energy and fatty acids (FAs) when fed to juvenile (32 g) Atlantic salmon (Salmo salar L.). Four isonitrogenous (50% crude protein), isolipidic (20% lipid) and isocaloric (19 MJ/kg digestible energy) practical-ingredient experimental diets were formulated to replace 0, 33, 66 and 100% of dietary fish oil with extracted Schizochytrium sp. (T18) oil. The oil used contained 50% polyunsaturated FAs (PUFA); of which 82% (e.g., 42% of total FAs) was comprised of the dietary n-3 long-chain PUFA (n-3 LC-PUFA) DHA and contained extremely low levels of harmful contaminants (e.g., heavy metals, lipid oxidation products, pathogens). Partial or complete replacement of dietary fish oil with Schizochytrium sp. (T18) oil had no significant (P ≥ .064) effects on AD of dietary dry matter (76–77%), protein (94%), lipid (89–90%) or energy (83–84%). Similarly, AD was unaffected (P ≥ .647) for dietary PUFA (97%) and n-3 PUFA (98%) with only minor differences (P ≤ .046) detected for monounsaturated FAs (MUFA; 91–92%) and n-6 PUFA (95–96%). Alternatively, AD of dietary saturated FAs (SFA) and DHA were significantly (P < .001) improved (70–76% and 95–98%, respectively) with increasing replacement of fish oil with Schizochytrium sp. (T18) oil. Results suggest that conventional fish oil can be completely replaced in juvenile farmed salmon feeds by Schizochytrium sp. (T18) oil with no negative effects on digestibility of dietary proximate nutrients, energy or fatty acids and, in fact, promoting a significant linear dose-response increase in AD of dietary SFA and a statistically significant increase in dietary DHA digestibility.

Effect of eating habits, BMI value, physical activity and smoking cigarettes on blood lipid indices of adolescent boys from Poland.

The lifestyle of young boys has impact on the risks of cardiovascular diseases. The aim of the study was to evaluate the effect of atherosclerosis risk factors determined by overweight and obesity and lifestyle, i.e.: eating habits, low physical activity and smoking cigarettes, on blood lipid profile of boys at the age of 16 to 18. The study covered 369 boys from secondary schools. They were evaluated for the supply of dietary constituents with atherogenic and protective actions, for nutritional status acc. to Cole's criteria, the level of physical activity, and smoking cigarettes. Lipid metabolism was determined based on criteria recommended by the American National Cholesterol Education Program (NCEP). Logistic regression analysis was conducted and risk odds ratio [OR] was determined. Analyses showed the boys to be characterized by overweight (10.8%) and obesity (2.7%), and by inappropriate concentration of total cholesterol (26.5%), LDL (13.3%), HDL (21.7%) and triglycerides (41.7%). High BMI turned out to be a significant risk factor of an elevated total cholesterol concentration: [aOR]=2.27; triglycerides: [aOR]=2.35 and LDL: [aOR]=2.41. Low physical activity was found to negatively affect the concentration of LDL: [aOR]=1.88. The boys smoking cigarettes were shown to have a reduced HDL: [aOR]=1.65. The total content of fat and saturated fatty acids in diet exerted a significantly negative impact on blood lipid profile of the boys. The lifestyle of the young boys was demonstrated to determine the risk of cardiovascular diseases. Overweight and obesity, abdominal obesity in particular, were found to be a significant risk factor of disorders in their lipid metabolism.

Serum cytokeratin 18 level is associated with dietary intake and serum triglycerides level in hemodialysis patients.

Cell death leads to increase serum cytokeratin 18 (CK-18) in chronic kidney disease. However, few studies have investigated the serum CK-18 level in relation to nutritional and metabolic biomarkers. We examined the association of dietary intake and lipid profile with serum CK18 level among hemodialysis (HD) patients. Ninety HD patients according to inclusion and exclusion criteria were included in the study. An analysis of clinical characteristics, anthropometric indices, dietary intake, and lipid profile revealed a significant association between serum CK-18 and diabetes, metabolic syndrome, body mass index (BMI), triglyceride (TG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), energy intake (EI), protein intake (PI), and saturated fatty acid (SFA). In a multiple stepwise regression model, after adjusting for confounders in three models, the association between serum CK-18 and serum TG level, dietary SFA and EI remained significant. The model 3 adjusted for DM, Mets, BMI, ALT, AST, and PI; model 2 adjusted for model 1 + EI; and model 1 adjusted for model 2 + SFA. Our findings suggest that the development of hypertriglyceridemia and inadequate EI contribute to higher serum CK-18, which is a cell death biomarker.

Reproducibility and construct validity of a food frequency questionnaire for assessing dietary intake in rural and urban Asian Indian adults.

To evaluate the reproducibility and construct validity of the Madras Diabetes Research Foundation FFQ (MDRF-FFQ) with biomarkers for its use in epidemiological settings in India. The MDRF-FFQ was administered to 500 participants representing rural and urban areas of 10 Indian states, twice at an interval of 12 months. Reproducibility was assessed using intra cluster correlation coefficients (ICC). Construct validity of carbohydrate and fat intake was assessed using baseline serum lipids by regression analysis. Reproducibility as measured by ICC was 0.50-0.77 for saturated fatty acids (SFA) and energy in urban and 0.61-0.72 for protein and SFA in rural areas. The ICC for food groups was 0.53-0.77 for whole grains, fruits and vegetables in urban and 0.50-0.89 for animal foods and whole grains in rural areas. After adjusting for potential confounders, carbohydrate intake was positively associated with serum triglycerides (TG) (β [SE]: +2.3 [0.72] mg/dL; p=0.002) and inversely with high density lipoprotein cholesterol (HDL) (β [SE]:-0.48 [0.12], p<0.001), while dietary fat and SFA (% Energy) were positively associated with HDL, low density lipoprotein (LDL) and total cholesterol and inversely with TG. The MDRF-FFQ can be considered as a reliable and valid tool to measure the long-term dietary exposure in respect of macronutrient intakes in Indian populations despite diverse dietary practices.

Palmitate and Nitric Oxide Regulate the Expression of Spexin and Galanin Receptors 2 and 3 in Hypothalamic Neurons

Spexin (SPX) is a novel satiety factor that putatively binds the galanin receptors R2 and R3 (GalR2/R3). SPX reduces body weight, and circulating SPX is decreased in obesity. It is unknown how SPX and its receptors are regulated in the hypothalamus, critical for energy homeostasis. We therefore examined the regulation of hypothalamic Spx, GalR2 and GalR3 gene expression in mouse primary and immortalized hypothalamic neurons. We report that Spx, GalR2 and GalR3 mRNA levels were regulated by acute treatments of palmitate, a dietary saturated fatty acid, as well as the nitric oxide (NO) donor sodium nitroprusside (SNP), but through a pathway independent of cyclic GMP and protein kinase G. Additionally, the palmitate- and NO-mediated induction of Spx and galanin receptors was blocked with the PKC inhibitor k252c. Furthermore, palmitate induced mRNA levels of endoplasmic reticulum (ER) stress markers, including Chop, Grp78 and Bax/Bcl2, as well as C/ebp-β, whereas SNP induced Bax/Bcl2 and C/ebp-β. Transcriptional changes in Spx, GalR2, GalR3, C/ebp-β and ER stress marker mRNAs were blocked by pre-treatment with at least one of the chemical chaperones PBA or TUDCA. We also describe the presence of OCT-1 and C/EBP-β response elements in the 5′ regulatory region of Spx and demonstrate that SNP increases binding of C/EBP-β to this region, but not Oct-1 mRNA nor OCT-1 binding. Our findings suggest an acute modulation of anorexigenic SPX signaling by palmitate and NO. Furthermore, ER stress and C/EBP-β appear to mediate the changes in Spx, GalR2 and GalR3 in hypothalamic neurons.

Postprandial triglyceride-rich lipoproteins promote M1/M2 microglia polarization in a fatty-acid-dependent manner

Inhibiting M1 microglia phenotype while stimulating the M2 microglia has been suggested as a potential therapeutic approach for the treatment of neuroinflammatory diseases. Our hypothesis is that the type of dietary fatty acids (FAs) into human postprandial triglyceride-rich lipoproteins (TRLs) could modulate the plasticity of microglia. We isolated TRLs at the postprandial hypertriglyceridemic peak from blood samples of healthy volunteers after the ingestion of a meal rich in saturated FAs (SFAs), monounsaturated FAs (MUFAs) or MUFAs plus omega-3 long-chain polyunsaturated FAs. We observed that postprandial TRL-MUFAs enhance M2 microglia polarization, whereas postprandial TRL-SFAs made polarized microglia prone to an M1 phenotype. In addition, in contrast to dietary SFAs, dietary MUFAs primed for a reduced proinflammatory profile in the brain of mice fed with the different FA-enriched diets. Our study underlines a role of postprandial TRLs as a metabolic entity in regulating the plasticity of microglia and brings an understanding of the mechanisms by which dietary FAs are environmental factors fostering the innate immune responsiveness. These exciting findings open opportunities for developing nutraceutical strategies with olive oil as the principal source of MUFAs, notably oleic acid, to prevent development and progression of neuroinflammation-related diseases.

Dietary saturated fat intake and risk of stroke: Systematic review and dose–response meta-analysis of prospective cohort studies

Background and aimsBecause of the conflicting research results, the association between saturated fatty acid (SFA) consumption and the risk of stroke remains controversial. We conducted a meta-analysis to evaluate potential dose–response relation between SFA intake and stroke. Methods and resultsPubMed, Embase, the Cochrane Library Central Register of Controlled Trials, and Web of Science were searched. Summary relative risks (RRs) of the highest vs. the lowest category of SFA intake and their 95% confidence intervals (CIs) were pooled by random-effects models. Linear or nonlinear dose–response trend estimations were evaluated with data from categories of SFA consumption in each study. Fourteen studies involving a total of 598,435 participants were eligible for high vs. low meta-analysis, and 12 studies involving a total of 462,268 participants were eligible for the dose–response relation assessment. Higher dietary SFA intake was associated with a decreased overall risk for stroke (RR, 0.87; 95% CI, 0.78–0.96; I2 = 37.8%). A linear relation between SFA and stroke was explored (P = 0.01), the pooled RR of stroke per 10 g/day increase in SFA intake was 0.94 (95% CI, 0.89–0.98; P = 0.01). ConclusionThis meta-analysis further demonstrated that a higher consumption of dietary SFA is associated with a lower risk of stroke, and every 10 g/day increase in SFA intake is associated with a 6% relative risk reduction in the rate of stroke. Further research is needed to explore the influence of specific SFA types and different macronutrient replacement models of SFA on the stroke risk.

Potential relationship between dietary long-chain saturated fatty acids and hypothalamic dysfunction in obesity.

Diet-induced hypothalamic inflammation, which leads to hypothalamic dysfunction and a loss of regulation of energy balance, is emerging as a potential driver of obesity. Excessive intake of long-chain saturated fatty acids is held to be the causative dietary component in hypothalamic inflammation. This review summarizes current evidence on the role of long-chain saturated fatty acids in promoting hypothalamic inflammation and the related induction of central insulin and leptin insensitivity. Particularly, the present review focuses on the molecular mechanisms linking long-chain saturated fatty acids and hypothalamic inflammation, emphasizing the metabolic fate of fatty acids and the resulting lipotoxicity, which is a key driver of hypothalamic dysfunction. In conclusion, long-chain saturated fatty acids are key nutrients that promote hypothalamic inflammation and dysfunction by fostering the build-up of lipotoxic lipid species, such as ceramide. Furthermore, when long-chain saturated fatty acids are consumed in combination with high levels of refined carbohydrates, the proinflammatory effects are exacerbated via a mechanism that relies on the formation of advanced glycation end products.

Potential Interplay between Dietary Saturated Fats and Genetic Variants of the NLRP3 Inflammasome to Modulate Insulin Resistance and Diabetes Risk: Insights from a Meta-Analysis of 19005 Individuals.

ScopeInsulin resistance (IR) and inflammation are hallmarks of type 2 diabetes (T2D). The nod‐like receptor pyrin domain containing‐3 (NLRP3) inflammasome is a metabolic sensor activated by saturated fatty acids (SFA) initiating IL‐1β inflammation and IR. Interactions between SFA intake and NLRP3‐related genetic variants may alter T2D risk factors.MethodsMeta‐analyses of six Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (n = 19 005) tested interactions between SFA and NLRP3‐related single‐nucleotide polymorphisms (SNPs) and modulation of fasting insulin, fasting glucose, and homeostasis model assessment of insulin resistance.ResultsSFA interacted with rs12143966, wherein each 1% increase in SFA intake increased insulin by 0.0063 IU mL−1 (SE ± 0.002, p = 0.001) per each major (G) allele copy. rs4925663, interacted with SFA (β ± SE = −0.0058 ± 0.002, p = 0.004) to increase insulin by 0.0058 IU mL−1, per additional copy of the major (C) allele. Both associations are close to the significance threshold (p < 0.0001). rs4925663 causes a missense mutation affecting NLRP3 expression.ConclusionTwo NLRP3‐related SNPs showed potential interaction with SFA to modulate fasting insulin. Greater dietary SFA intake accentuates T2D risk, which, subject to functional validation, may be further elaborated depending on NLRP3‐related genetic variants.

Dairy Fat Consumption and the Risk of Metabolic Syndrome: An Examination of the Saturated Fatty Acids in Dairy.

Lifestyle is a key modifiable risk factor involved in the manifestation of metabolic syndrome and, in particular, diet plays a pivotal role in its prevention and development. Current dietary guidelines discourage the consumption of saturated fat and dietary sources rich in saturated fat, such as dairy products, despite data suggesting that full-fat dairy consumption is protective against metabolic syndrome. This narrative review assessed the recent epidemiological and clinical research that examined the consumption of dairy-derived saturated fatty acids (SFA) on metabolic syndrome risk. In addition, this review evaluated studies of individual SFA to gain insight into the potential mechanisms at play with intake of a diet enriched with these dairy-derived fatty acids. This work underscores that SFA are a heterogenous class of fatty acids that can differ considerably in their biological activity within the body depending on their length and specific chemical structure. In summary, previous work on the impact of dairy-derived SFA consumption on disease risk suggests that there is currently insufficient evidence to support current dietary guidelines which consolidate all dietary SFA into a single group of nutrients whose consumption should be reduced, regardless of dietary source, food matrix, and composition.

The Involvement of Peripheral and Brain Insulin Resistance in Late Onset Alzheimer's Dementia.

Nowadays, Alzheimer’s disease (AD) is a severe sociological and clinical problem. Since it was first described, there has been a constant increase in its incidence and, for now, there are no effective treatments since current approved medications have only shown short-term symptomatic benefits. Therefore, it is imperative to increase efforts in the search for molecules and non-pharmacological strategies that are capable of slowing or stopping the progress of the disease and, ideally, to reverse it. The amyloid cascade hypothesis based on the fundamental role of amyloid has been the central hypothesis in the last 30 years. However, since amyloid-directed treatments have shown no relevant beneficial results other theories have been postulated to explain the origin of the pathology. The brain is a highly metabolically active energy-consuming tissue in the human body. It has an almost complete dependence on the metabolism of glucose and uses most of its energy for synaptic transmission. Thus, alterations on the utilization or availability of glucose may be cause for the appearance of neurodegenerative pathologies like AD. In this review article, the hypothesis known as Type 3 Diabetes (T3D) will be evaluated by summarizing some of the data that has been reported in recent years. According to published research, the adherence over time to low saturated fatty acids diets in the context of the Mediterranean diet would reduce the inflammatory levels in brain, with a decrease in the pro-inflammatory glial activation and mitochondrial oxidative stress. In this situation, the insulin receptor pathway would be able to fine tune the mitochondrial biogenesis in neuronal cells, regulation the adenosine triphosphate/adenosine diphosphate intracellular balance, and becoming a key factor involved in the preservation of the synaptic connexions and neuronal plasticity. In addition, new targets and strategies for the treatment of AD will be considered in this review for their potential as new pharmacological or non-pharmacological approaches.

Long term effect of dietary lipid saturation on eggshell quality and bone characteristics of laying hens.

This study investigated the long-term effect of dietary fatty acid saturation on eggshell quality and bone characteristics of laying hens at end of lay. Five isoenergetic (3,011.5 kcal AME/kg DM) and isonitrogenous (169 g CP/kg DM) diets were formulated using different lipid sources at a constant 30 g/kg inclusion level. The control, polyunsaturated omega-3 (PUFA n-3), polyunsaturated omega-6 (PUFA n-6), monounsaturated omega-9 (MUFA n-9), and saturated fatty acid (SFA) diets consisted of linseed- and fish oil (50:50 blend), fish oil, sunflower oil, high oleic acid sunflower oil, and tallow, respectively. A total of 200 individually caged Hy-Line Silver-Brown hens (20 wk of age) were randomly allocated to the 5 treatments (n = 40 replicates/treatment) and received the experimental diets for 54 wk. During weeks 58, 62, 66, 70, and 74 of age (end-of-lay period), 20 eggs/treatment per day (n = 140 eggs/treatment per week) were selected for determining eggshell quality traits. At 74 wk of age, 10 birds per treatment (n = 10 birds/treatment) were randomly selected for the determination of bone quality characteristics. Data were statistically analyzed (P < 0.05) using a fully randomized 1-way ANOVA. Dietary treatment had no effect (P > 0.05) on eggshell quality traits. The MUFA n-9 treatment with the highest unsaturated to SFA ratio (UFA: SFA) resulted in a higher (P < 0.05) femur weight (10.34 g) as well as femur- (52.99%) and tibia ash (51.07%) content than the SFA treatment. Also, the PUFA n-3 diet resulted in a higher (P < 0.05) femur weight (10.21 g), femur ash (51.82%), and percentage femur (0.57%) compared to the SFA diet. Results suggested that prolonged feeding of diets varying in FA profile had no negative effect on eggshell quality, whereas UFA: SFA and long-chain n-3 PUFA affected the bone quality (especially the femur) of hens at the end of lay.

Dietary Fatty Acid Saturation Modulates Sphingosine-1-Phosphate-Mediated Vascular Function

Sphingolipids, modified by dietary fatty acids, are integral components of plasma membrane and caveolae that are also vasoactive compounds. We hypothesized that dietary fatty acid saturation affects vasoconstriction to sphingosine-1-phosphate (S1P) through caveolar regulation of rho kinase. Wild type (WT) and caveolin-1-deficient (cav-1 KO) mice which lack vascular caveolae were fed a low-fat diet (LF), 60% high-saturated fat diet (lard, HF), or 60% fat diet with equal amounts of lard and n-3 polyunsaturated menhaden oil (MO). Weight gain of WT on HF and MO diets was similar while markedly blunted in cav-1 KO. Neither high-fat diet affected the expression of cav-1, rho, or rho kinase in arteries from WT. In cav-1 KO, MO increased the vascular expression of rho but had no effect on rho kinase. HF had no effect on rho or rho kinase expression in cav-1 KO. S1P produced a concentration-dependent constriction of gracilis arteries from WT on LF that was reduced with HF and restored to normal with MO. Constriction to S1P was reduced in cav-1 KO and no longer affected by a high-saturated fat diet. Inhibition of rho kinase which reduced constriction to PE independent of diet in arteries from WT and cav-1 KO only reduced constriction to S1P in arteries from WT fed MO. The data suggest that dietary fatty acids modify vascular responses to S1P by a caveolar-dependent mechanism which is enhanced by dietary n-3 polyunsaturated fats.

Dietary Intake of Fatty Acids, Total Cholesterol, and Stomach Cancer in a Chinese Population.

To investigate the associations between dietary fatty acids and cholesterol consumption and stomach cancer (SC), we analyzed data from a population-based case-control study with a total of 1900 SC cases and 6532 controls. Dietary data and other risk or protective factors were collected by face-to-face interviews in Jiangsu Province, China, from 2003 to 2010. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multiple unconditional logistic regression models and an energy-adjusted method. The joint associations between dietary factors and known risk factors on SC were examined. We observed positive associations between dietary saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and total cholesterol and the development of SC, comparing the highest versus lowest quarters. Increased intakes of dietary SFAs (p-trend = 0.005; aOR, 1.11; 95% CI, 1.01–1.22 with a 7 g/day increase as a continuous variable) and total cholesterol (p-trend < 0.001; aOR, 1.13; 95% CI, 1.06–1.22 with a 250 mg/day increase as a continuous variable) were monotonically associated with elevated odds of developing SC. Our results indicate that dietary SFAs, MUFAs, and total cholesterol are associated with stomach cancer, which might provide a potential dietary intervention for stomach cancer prevention.

Dietary Saturated Fat Is Associated with Larger LDL Particle Size and Reduced CVD Risk in Framingham Offspring Study (P08-128-19)

ObjectivesSmall dense LDL particles have been shown to promote atherogenic cardiovascular disease (CVD). Dietary fat type may impact LDL particle size, but few studies have examined the association between fatty acid intake and LDL particle size and CVD risk. Our goal was to examine the association of saturated fatty acid (SFA) intake with LDL particle size and CVD risk in subjects in the Framingham Offspring Study (FOS). MethodsLDL particle profiles were measured by NMR spectroscopic assay during exam visit 4 in the prospective FOS. Dietary fat, carbohydrate and food groups were assessed using 3-day diet records at exams 3 and 5; intakes were adjusted for body weight using the residuals from linear regression models. Multivariable Cox proportional hazards models and generalized linear modeling (GLM) were used to adjust for sex, age, height, pack-years of smoking, fruit and non-starchy vegetable intakes, dairy, LDL particle size, and prevalent hypertension. ResultsSubjects were classified into 6 categories using the combined intakes of carbohydrates (<48% vs. ≥48% of calories) and weight-adjusted SFA (<20, 20-<30, ≥30 g/day). Among those with higher carbohydrate intake, increasing levels of dietary SFA were associated with reduced risk of CVD. Specifically, those with the highest SFA intake and higher energy-adjusted carbohydrate intakes had a 56% (CI: 0.24–0.82) lower risk of CVD compared with those who had both low SFA and lower carbohydrate intakes. Moreover, increasing SFA intake among those with higher carbohydrate intakes was also associated with larger LDL particle sizes (P = 0.04, highest SFA intake vs. lowest SFA intake). Among low-carbohydrate consumers, SFA intake was not associated with risk of CVD, but was still positively associated with larger LDL particle size (P = 0.0003, highest SFA intake vs. lowest SFA intake). ConclusionsSFA intake was associated with larger LDL particle sizes regardless of carbohydrate intakes. However, a higher SFA intake was only associated with reduced CVD risk among those with higher carbohydrate intakes. Funding SourcesNational Dairy Council.

Dietary patterns influence epicardial adipose tissue fatty acid composition and inflammatory gene expression in the Ossabaw pig

Epicardial adipose tissue (EAT) inflammation is implicated in the development and progression of coronary atherosclerosis. Dietary saturated and polyunsaturated fatty acids (SFAs and PUFA) can influence adipose tissue inflammation. We investigated the influence of dietary patterns, with emphasis on dietary fat type, and statin therapy, on EAT fatty acid (FA) composition and inflammatory gene expression. Thirty-two Ossabaw pigs were fed isocaloric amounts of a Heart Healthy (high in unsaturated fat) or Western (high in saturated fat) diets +/− atorvastatin for 6 months. EAT FA composition reflected dietary fat composition. There was no significant effect of atorvastatin on EAT FA composition. Total and long-chain SFAs were positively associated with inflammatory signaling (TLR2) and a gene involved in lipid mediator biosynthesis (PTGS2) (P<.0003). Medium-chain SFAs capric and lauric acids were negatively associated with IL-6 (all P<.0003). N-6 and n-3 PUFAs were positively associated with anti-inflammatory signaling genes (PPARG, FFAR4 and ADIPOQ) and long-chain n-3 PUFAs were positively associated with a gene involved in lipid mediator biosynthesis (ALOX5) (all P<.0003). These data indicate that dietary patterns, differing in fat type, influence EAT FA composition. Associations between EAT SFAs, PUFAs, and expression of genes related to inflammation provide a link between dietary quality and EAT inflammation.

Using metabolic profiling and gene expression analyses to explore molecular effects of replacing saturated fat with polyunsaturated fat—a randomized controlled dietary intervention study

ABSTRACTBackgroundReplacing dietary saturated fatty acids (SFAs) with polyunsaturated fatty acids (PUFA) reduces the plasma low-density lipoprotein (LDL) cholesterol and subsequently the risk of cardiovascular disease. However, beyond changes in LDL cholesterol, we lack a complete understanding of the physiologic alterations that occur when improving dietary fat quality.ObjectivesThe aim of this study was to gain knowledge of metabolic alterations paralleling improvements in the fat quality of the diet.MethodsWe recently conducted an 8-wk, double-blind, randomized controlled trial replacing SFAs with PUFAs in healthy subjects with moderate hypercholesterolemia (n = 99). In the present substudy, we performed comprehensive metabolic profiling with multiple platforms (both nuclear magnetic resonance- and mass spectrometry-based technology) (n = 99), and analyzed peripheral blood mononuclear cell gene expression (n = 95) by quantitative real-time polymerase chain reaction.ResultsA large number of lipoprotein subclasses, myristoylcarnitine and palmitoylcarnitine, and kynurenine were reduced when SFAs were replaced with PUFAs. In contrast, bile acids, proprotein convertase subtilisin/kexin type 9, acetate, and acetoacetate were increased by the intervention. Some amino acids were also altered by the intervention. The mRNA levels of LXRA and LDLR were increased, in addition to several liver X receptor α target genes and genes involved in inflammation, whereas the mRNA levels of UCP2 and PPARD were decreased in peripheral blood mononuclear cells after replacing SFAs with PUFAs. Partial least squares-discriminant analysis showed that the 30 most important variables that contributed to class separation spanned all classes of biomarkers, and was in accordance with the univariate analysis.ConclusionsApplying metabolomics in randomized controlled dietary intervention trials has the potential to extend our knowledge of the biological and molecular effects of dietary fat quality. This study was registered at clinicaltrials.gov as NCT 01679496.

SAT-403 Palmitoleate Reverses Palmitate-Induced Autophagy

Autophagy is a well-known process that regulates cellular homeostasis by degrading malformed organelles and dysfunctional proteins. Normal autophagy is crucial to maintain the functionality of hypothalamic neurons, which are important in regulating energy balance. Fatty acids can be sensed by hypothalamic neurons and affect cell viability, inflammation and metabolic pathways. We recently found that the most prevalent dietary saturated fatty acid palmitate (PA) was able to induce hypothalamic autophagy by as yet undefined mechanisms. We are currently investigating if an unsaturated fatty acid palmitoleate (PO) has any effect on autophagy modulation. Given that unsaturated fatty acids protect other cells from palmitate-mediated dysfunction, we hypothesized that palmitoleate could protect neurons from palmitate-induced autophagy. We used the clonal, embryonic male, mHypoE-46, and adult-derived male, mHypoA-2/29, neuronal cell lines to evaluate autophagy modulation in response to palmitoleate (PO) treatment. Neurons were first treated with 25, 50 or 250 µM of PO alone. In the mHypoE-46 cells, the highest 250 µM concentration of PO was extremely toxic to the cells, as determined by cell death. In order to measure autophagy vacuoles (autophagosomes and autolysossomes) flow cytometry technique was performed. Partial data suggested that 25 and 50 µM PO was able to reduce overall autophagy. When we performed a co-treatment using PA (25 µM) and PO (25 µM), we observed that PA-mediated autophagy induction was blocked. In the mHypoA-2/29 cells, all concentrations of PO alone, including 250 µM, were able to reduce autophagy modulation, as detected by flow cytometry. We also tested the effect of a mixture of multiple saturated and unsaturated fatty acids (palmitate, stearic, oleic, linoleic and arachidonic) in the mHypoE-46 cells and found that this mixture did not affect autophagy. Thus, the saturated fatty acid PA increases autophagy, and we present evidence that an unsaturated fatty acid PO may rescue this induction, contributing to an overall protective response in neurons. We are now investigating the molecular mechanisms by which specific fatty acids control neuronal autophagy and predict that these will be unique to saturated versus unsaturated fatty acids. Understanding how fatty acids affect autophagy in neurons that control food intake could potentially represent a promising therapeutic target against obesity.