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Abnormal Myocardial Dietary Fatty Acid Metabolism and Diabetic Cardiomyopathy.
Carpentier, AC
The Canadian journal of cardiology. 2018;(5):605-614
Abstract
Patients with diabetes are at very high risk of hospitalization and death from heart failure. Increased prevalence of coronary heart disease, hypertension, autonomic neuropathy, and kidney failure all play a role in this increased risk. However, cardiac metabolic abnormalities are now recognized to play a role in this increased risk. Increased reliance on fatty acids to produce energy might predispose the diabetic heart to oxidative stress and ischemic damage. Intramyocellular accumulation of toxic lipid metabolites leads to a number of cellular abnormalities that might also contribute to cardiac remodelling and cardiac dysfunction. However, fatty acid availability from circulation and from intracellular lipid droplets to fuel the heart is critical to maintain its function. Fatty acids delivery to the heart is very complex and includes plasma nonesterified fatty acid flux as well as triglyceride-rich lipoprotein-mediated transport. Although many studies have shown a cross-sectional association between enhanced fatty acid delivery to the heart and reduction in left ventricular function in subjects with prediabetes and diabetes, these mechanisms change very rapidly during type 2 diabetes treatment. The present review focuses on the role of fatty acids in cardiac function, with particular emphasis on the possible role of early abnormalities of dietary fatty acid metabolism in the development of diabetic cardiomyopathy.
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Modification of Erythrocyte Membrane Fatty Acid Contents After Kidney Transplantation: A Prospective Study.
Son, YK, Kwon, H, Lee, HW, Jeong, EG, Lee, SM, Kim, SE, Park, Y, An, WS
Transplantation proceedings. 2018;(5):1332-1335
Abstract
BACKGROUND Modifications of erythrocyte membrane fatty acid (FA) contents may affect cellular function or transmembrane receptors. One cross-sectional study has shown that kidney transplant (KTP) recipients have lower erythrocyte membrane oleic acid content than dialysis patients do. Therefore, we prospectively tested whether erythrocyte membrane contents of FA including oleic acid change after KTP. METHODS We recruited 23 KTP recipients (September 2011 through May 2014). Blood samples were obtained immediately before KTP and 6 months after. Erythrocyte membrane FA contents were measured by gas chromatography. RESULTS Mean age of the enrolled KTP recipients was 45.3 ± 10.9 years, and men represented 66.7% of the cases. ABO-incompatible KTPs constituted 14.3% and cadaver donors 42.9% of the cases. Steroids, mycophenolate mofetil, and tacrolimus were used as immunosuppressive treatment. There was no significant difference in dietary consumption between time points before and 6 months after KTP. Total cholesterol and low-density lipoprotein cholesterol levels were significantly higher at 6 months after KTP as compared with baseline. Erythrocyte membrane contents of polyunsaturated FA, ω-3 FA, ω-6 FA, and the ω-3 index were significantly higher, but erythrocyte membrane contents of total saturated FAs, total monounsaturated FAs, including oleic acid, total trans-FA, palmitoleic acid, and the ω-6-to-ω-3 ratio were significantly lower at 6 months after KTP. CONCLUSIONS Erythrocyte membrane FA contents significantly changed toward a more favorable cardiovascular profile after KTP. These changes in erythrocyte membrane FA contents may be related to improved renal function because of the absence of significant dietary changes.
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3.
Blood Fatty Acid Profiles: New Biomarkers for Cardiometabolic Disease Risk.
Jackson, KH, Harris, WS
Current atherosclerosis reports. 2018;(5):22
Abstract
PURPOSE OF REVIEW Fatty acid (FA) profiles in different blood compartments are reflections of both diet and metabolism, and some FA levels are related to disease risk. RECENT FINDINGS Perhaps the most studied FA-disease relationship is between long-chain omega-3 polyunsaturated fatty acids [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] and cardiovascular disease (CVD). Despite null results from recent large omega-3 FA supplementation trials, new research continues to support past studies showing that blood levels of EPA + DHA are inversely related to risk for total mortality and fatal CVD events. But blood levels of other FAs may also be useful markers of risk for a variety of diseases. The essential omega-6 FA linoleic acid is inversely associated with risk for developing type 2 diabetes (T2D), whereas risk for T2D is directly related to biomarkers of de novo lipogenesis (palmitic and palmitoleic acids). Levels of industrially produced trans FAs have been linked to higher risk for CVD. Thus, blood levels of several individual FAs are emerging as modifiable biomarkers for risk of major chronic diseases.
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Absorption and Safety With Sustained Use of RELiZORB Evaluation (ASSURE) Study in Patients With Cystic Fibrosis Receiving Enteral Feeding.
Stevens, J, Wyatt, C, Brown, P, Patel, D, Grujic, D, Freedman, SD
Journal of pediatric gastroenterology and nutrition. 2018;(4):527-532
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Abstract
OBJECTIVES Pancreatic insufficiency (PI) and malabsorption of fats lead to reduced caloric intake, inability to maintain weight, and increased gastrointestinal symptoms. Thus, enteral nutrition (EN) is used in patients with cystic fibrosis (CF) and poor nutritional status. The current study evaluated safety, tolerability, and improvement of fatty acid (FA) status in red blood cell (RBC) membranes, a marker of long-term FA absorption, with an in-line digestive cartridge (RELiZORB) that hydrolyzes fat in enteral formula. METHODS Patients with CF receiving EN participated in a multicenter, 90-day open-label study during which RELiZORB was used with overnight EN. The primary endpoint was change over time in RBC uptake of docosahexaenoic acid (DHA)+ eicosapentaenoic acid (EPA). Gastrointestinal symptoms were collected to evaluate safety and tolerability. Several clinical and anthropometric parameters were also assessed throughout the study. RESULTS A total of 36 subjects completed the study with a mean age of 13.8 years, body mass index of 17.7 and 6.2 years mean use of overnight EN. Fat absorption significantly improved as shown by increased RBC levels of DHA+EPA, improved ω-6/ω-3 ratio, and increased plasma levels of DHA+EPA. RELiZORB use was not associated with any unanticipated adverse events. CONCLUSIONS RELiZORB use was found to be safe, well tolerated, and resulted in increased levels of FAs in RBCs and plasma. This is the first prospective study to show EN can improve FA abnormalities in CF. Because improvement in omega-3 levels has been shown to help pulmonary and inflammatory status as well as anthropometric parameters in CF, RELiZORB may have important long-term therapeutic benefits in patients with CF.
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Fatty acid profile in peri-prostatic adipose tissue and prostate cancer aggressiveness in African-Caribbean and Caucasian patients.
Figiel, S, Pinault, M, Domingo, I, Guimaraes, C, Guibon, R, Besson, P, Tavernier, E, Blanchet, P, Multigner, L, Bruyère, F, et al
European journal of cancer (Oxford, England : 1990). 2018;:107-115
Abstract
BACKGROUND Genetic and nutritional factors have been linked to the risk of aggressive prostate cancer (PCa). The fatty acid (FA) composition of peri-prostatic adipose tissue (PPAT), which reflects the past FA intake, is potentially involved in PCa progression. We analysed the FA composition of PPAT, in correlation with the ethno-geographical origin of the patients and markers of tumour aggressiveness. METHODS From a cohort of 1000 men treated for PCa by radical prostatectomy, FA composition of PPAT was analysed in 156 patients (106 Caucasians and 50 African-Caribbeans), 78 with an indolent tumour (ISUP group 1 + pT2 + PSA <10 ng/mL) and 78 with an aggressive tumour (ISUP group 4-5 + pT3). The effect of FA extracted from PPAT on in-vitro migration of PCa cells DU145 was studied in 72 patients, 36 Caucasians, and 36 African-Caribbeans. RESULTS FA composition differed according to the ethno-geographical origin. Linoleic acid, an essential n-6 FA, was 2-fold higher in African-Caribbeans compared with Caucasian patients, regardless of disease aggressiveness. In African-Caribbeans, the FA profile associated with PCa aggressiveness was characterised by low level of linoleic acid along with high levels of saturates. In Caucasians, a weak and negative association was observed between eicosapentaenoic acid level (an n-3 FA) and disease aggressiveness. In-vitro migration of PCa cells using PPAT from African-Caribbean patients was associated with lower content of linoleic acid. CONCLUSION These results highlight an important ethno-geographical variation of PPAT, in both their FA content and association with tumour aggressiveness.
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Greater expression of postprandial inflammatory genes in humans after intervention with saturated when compared to unsaturated fatty acids.
Monfort-Pires, M, Crisma, AR, Bordin, S, Ferreira, SRG
European journal of nutrition. 2018;(8):2887-2895
Abstract
INTRODUCTION Inflammation plays a key role in the development of insulin resistance and atherosclerosis. Fatty acids and fiber intake can selectively alter gene expression by modifying inflammation. PURPOSE We compared the postprandial expression of inflammatory genes after 2 distinct high-fat breakfast meals, before and after 1-month dietary interventions. METHODS This crossover clinical trial included 18 individuals at low-to-moderate cardiometabolic risk participating in evaluations before and after two 4-week breakfast interventions-one rich in saturated fatty acids (SFA) and the other in unsaturated fatty acids (unSFA) and fiber. Participants underwent meal tests with similar compositions to the breakfasts. Variables were compared by Student t test. The expression of inflammatory genes in leukocytes was analyzed using RT-PCR. RESULTS Before and after the intervention with the SFA-enriched breakfast, this meal test induced a higher relative postprandial IL-1β expression compared to the responses to the unSFA and fiber-enriched meal (p = 0.02). On the other hand, following the intervention with the unSFA-fiber-enriched breakfast, postprandial IL-6 expression showed a reduction tendency comparing to the pre-intervention value (p = 0.08). Although fasting IL-1β, IL-6, MCP-1 and IFN-γ expressions had not changed after interventions, their circulating levels increased after the SFA-enriched meal test but not after the unSFA meal (p value between changes < 0.05). CONCLUSIONS Our findings indicated that a single SFA-enriched meal is able to acutely induce the IL-1β expression and regularly consumed could trigger systemic inflammation, while increased unSFA consumption could attenuate the inflammatory status. Further investigations are needed to deepen understanding how dietary fatty acids and fiber influence cardiometabolic risk profile by modulating inflammatory gene expression and circulating biomarkers. CLINICAL TRIAL INFORMATION This study is registered at the Brazilian Registry of Clinical Trials (ReBEC ID RBR-98x6b5). Available at: http://www.ensaiosclinicos.gov.br .
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New perspectives on placental fatty acid transfer.
Lewis, RM, Childs, CE, Calder, PC
Prostaglandins, leukotrienes, and essential fatty acids. 2018;:24-29
Abstract
The human foetus depends on placental transfer for the fatty acids required for its growth and development. Long chain polyunsaturated fatty acids (LC-PUFAs) may specifically influence neurodevelopment. Therefore, it is important to understand the mechanisms of placental transfer of LC-PUFAs. The simple view of placental fatty acid transfer is that it occurs by diffusion down the maternal to foetal gradient, facilitated by membrane transporters. This view has been complicated by studies highlighting the role of placental metabolism in fatty acid transfer. Most fatty acids taken up by the placenta will be esterified and incorporated into lipid rather than diffusing directly across to the foetus. Furthermore, this esterification is likely to mean that placental intracellular "free" fatty acid concentrations are lower than in foetal plasma which would not be conducive to simple diffusion of fatty acids to the foetus. Placental structure poses additional questions, in particular how fatty acids cross the hydrophilic villous stroma separating the trophoblast from the endothelium and how they cross the endothelium itself. The understanding of placental fatty acid transfer needs to evolve to address these questions. The role of the placenta is not simply to mediate solute transfer; it is also a central endocrine organ of pregnancy. Placental-derived lipid mediators, such as prostaglandins, have well-established roles in parturition and, almost certainly, throughout gestation. Metabolic targeting of specific fatty acids to different lipid pools in the placenta may determine their availability as both nutrients and signalling molecules. Placental transfer will determine fatty acid availability within the foetus as well as influencing maternal levels. Fatty acids and their derivatives may also act as signals to the placenta indicating metabolic states in both mother and foetus. Placental uptake and metabolism of LC-PUFAs are important to meet both foetal and placental demands. This paper will review placental fatty acid transfer and metabolism and highlight issues which need to be addressed.
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Relationship between fatty acids intake and Clostridium coccoides in obese individuals with metabolic syndrome.
Jamar, G, Santamarina, AB, Dias, GC, Masquio, DCL, de Rosso, VV, Pisani, LP
Food research international (Ottawa, Ont.). 2018;:86-92
Abstract
Dietary habits exert a strong influence on gut microbial composition and may result in an imbalance of gut microbes, representing a predisposition to obesity and metabolic disorders. We aimed to investigate a potential relationship between gut bacterial species and metabolic parameters and dietary intake. Bacterial DNA was extracted from feces of 34 obese subjects with and without metabolic syndrome (MS and n-MS group, respectively). We then used real-time polymerase chain reaction (qPCR) for quantifying specific sequences to Akkermansia muciniphila, Bifidobacterium spp., Clostridium coccoides, and Lactobacillus spp. and analyzed them with respect to clinical characteristics. Our data showed that the MS group had a 6.7-fold higher level of C. coccoides in their stool samples than the n-MS group. The abundance of C. coccoides was positively correlated with a high intake of monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids. Furthermore, an excessive dietary level of MUFA was identified as a predictor of C. coccoides abundance. Alterations in the gut microbial ecology were positively correlated with levels of triacylglycerol in obese individuals. Therefore, the type and quantity of dietary fat may alter the gut microbial ecology in obese individuals with MS and may predispose them to dyslipidemia.
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Influence of subacute physical exercise on medium- and long-chain fatty acid profile in serum of individuals with overweight.
Wagmacker, DS, Petto, J, Fraga, AS, Mota, SKA, Andrade, LEA, Rodrigues, LEA, Ladeia, AM
Nutricion hospitalaria. 2018;(6):1310-1315
Abstract
OBJECTIVE to test the hypothesis that acute physical exercise would change the fatty acids in the serum of individuals with increased body weight. METHOD sixty-six sedentary women with excess weight were included in the sample (BMI = 29.6 ± 4.2). They were aged 24.4 ± 3.6 years and were randomly divided into control and exercise groups. After 12 hours fasting, basal blood collection was performed. Twelve hours after the first collection, the exercise group was submitted to a physical exercise session with energy expenditure of 250 kcal. The volunteers underwent a second blood collection 24 hours after the first one and dosed the fatty acids: pelargonic, azelaic, elaidic and oleic. RESULTS physical exercise did not change the fatty acid profile response for both the intragroup analysis and intergroup analysis. Exercise group: pelargonic (before = 0.12 ± 0.06% vs after = 0.15 ± 0.14%, p = 0.507); azelaic (before = 20.3 ± 10.5% vs after = 27.7 ± 25.4%, p = 0.295); elaidic (before = 0.03 ± 0.01% vs after = 0.04 ± 0.01%, p = 0.328); oleic (before = 16.1 ± 7.4% vs after = 20.3 ± 14.6%, p = 0.236). CONTROL GROUP pelargonic (before = 0.70 ± 0.45% vs after = 0.71 ± 0.51%, p = 0.776); azelaic (before = 62.1 ± 26% vs after = 57.1 ± 27%, p = 0.197); elaidic (before = 0.05 ± 0.02% mg/dl vs after = 0.05 ± 0.03%, p = 0.530); oleic (before = 26.8 ± 22.7% mg/dl vs after = 29.0 ± 22.4%, p = 0.525). CONCLUSION in women with overweight, low intensity physical exercise is not capable of changing the medium-chain fatty acids in the first 12 hours.
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Dietary Fatty Acid Modification for the Treatment of Aspirin-Exacerbated Respiratory Disease: A Prospective Pilot Trial.
Schneider, TR, Johns, CB, Palumbo, ML, Murphy, KC, Cahill, KN, Laidlaw, TM
The journal of allergy and clinical immunology. In practice. 2018;(3):825-831
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Abstract
BACKGROUND The high levels of eicosanoid production and the clinical efficacy of leukotriene-modifying pharmacotherapies for patients with aspirin-exacerbated respiratory disease (AERD) suggest that other interventions targeting arachidonic acid dysregulation may also improve disease control. OBJECTIVE To assess the utility of a high omega-3/low omega-6 diet for the treatment of AERD. METHODS Prospective, nonblinded dietary intervention in 10 adult patients with AERD at Brigham and Women's Hospital in Boston, MA. The primary objective was for subjects to reduce dietary omega-6 fatty acid consumption to less than 4 g/d and increase omega-3 intake to more than 3 g/d. The primary outcome was change in urinary leukotriene E4, with changes in other eicosanoids, platelet activation, lung function, and patient-reported questionnaires also assessed. RESULTS Of the 10 subjects who screened for the study, all 10 completed the dietary intervention. Urinary leukotriene E4 decreased by 0.17 ng/mg (95% CI, -0.29 to -0.04; P = .02) and tetranor prostaglandin D-M decreased by 0.66 ng/mg creatinine (95% CI, -1.21 to -0.11; P = .02). There was a 15.1-point reduction in the 22-item Sino-Nasal Outcome Test score (95% CI, -24.3 to -6.0; P = .01), a 0.27-point reduction in the 7-item Asthma Control Questionnaire score (95% CI, -0.52 to -0.03; P = .03), and no change in FEV1 % predicted (P = .92) or forced vital capacity % predicted (P = .74). All patients lost some weight over the 2-week intervention period, and there were no diet-associated adverse events. CONCLUSIONS A high omega-3/low omega-6 diet may be an appropriate adjunct treatment option for patients with AERD.