Substitution Of Fatty Acids Research Articles

An in vitro evaluation of partial energy replacement in a total mixed ration with volatile fatty acids derived from agro-industrial residues

AbstractThe scientific interest in volatile fatty acids (VFAs) as an energy source and chemical precursor in ruminant diets has been longstanding, as it has significant implications for animal physiology and well-being. The present study explores the substitution of volatile fatty acids (VFAs) derived from agro-food residues via acidogenic fermentation as an alternative energy source in ruminant feed. Utilizing the gas production method, rumen digestibility assays were conducted, wherein the recovered VFA effluent from the acidogenic fermentation of apple pomace and potato protein liquor was substituted for 10%, 20%, and 30% of the total mixed ration (TMR) energy. Various parameters such as gas, VFA yield and composition, VFA peak intervals, changes in pH, and ammonium nitrogen content were investigated. Based on the results obtained, provision of 20% and 30% of the energy with VFAs did not increase methane production or did not cause significant pH alternations. Nevertheless, such supplementation resulted in increased production and accumulation of VFAs in the rumen media. The bioconversion of agro-food side streams into VFAs opens a new path in sustainable nutrient recovery and feed production from low value agro-industrial residues. Graphical Abstract

Substitution of dietary monounsaturated fatty acids from olive oil for saturated fatty acids from lard increases low-density lipoprotein apolipoprotein B-100 fractional catabolic rate in subjects with dyslipidemia associated with insulin resistance: a randomized controlled trial

BackgroundThe substitution of monounsaturated acids (MUFAs) for saturated fatty acids (SFAs) is recommended for cardiovascular disease prevention but its impact on lipoprotein metabolism in subjects with dyslipidemia associated with insulin resistance (IR) remains largely unknown. ObjectivesThis study aimed to evaluate the impact of substituting MUFAs for SFAs on the in vivo kinetics of apolipoprotein (apo)B-containing lipoproteins and on the plasma lipidomic profile in adults with IR-induced dyslipidemia. MethodsMales and females with dyslipidemia associated with IR (n = 18) were recruited for this crossover double-blind randomized controlled trial. Subjects consumed, in random order, a diet rich in SFAs (SFAs: 13.4%E; MUFAs: 14.4%E) and a diet rich in MUFAs (SFAs: 7.1%E; MUFAs: 20.7%E) in fully controlled feeding conditions for periods of 4 wk each, separated by a 4-wk washout. At the end of each diet, fasting plasma samples were taken together with measurements of the in vivo kinetics of apoB-containing lipoproteins. ResultsSubstituting MUFAs for SFAs had no impact on triglyceride-rich lipoprotein apoB-48 fractional catabolic rate (FCR) (Δ = –8.9%, P = 0.4) and production rate (Δ = 0.0%, P = 0.9), although it decreased very low-density lipoprotein apoB-100 pool size (PS) (Δ = −22.5%; P = 0.01). This substitution also reduced low-density lipoprotein cholesterol (LDL-C) (Δ = −7.0%; P = 0.01), non–high-density lipoprotein cholesterol (Δ = −2.5%; P = 0.04), and LDL apoB-100 PS (Δ = −6.0%; P = 0.05). These differences were partially attributed to an increase in LDL apoB-100 FCR (Δ = +1.6%; P = 0.05). The MUFA diet showed reduced sphingolipid concentrations and elevated glycerophospholipid levels compared with the SFA diet. ConclusionsThis study demonstrated that substituting dietary MUFAs for SFAs decreases LDL-C levels and LDL PS by increasing LDL apoB-100 FCR and results in an overall improved plasma lipidomic profile in individuals with IR-induced lipidemia. Trial registrationThis trial was registered as clinicaltrials.gov as NCT03872349.

MiR-497 Regulates LATS1 through the PPARG Pathway to Participate in Fatty Acid Synthesis in Bovine Mammary Epithelial Cells.

Nutrient metabolism is required to maintain energy balance in animal organisms, and fatty acids play an irreplaceable role in fat metabolism. In this study, microRNA sequencing was performed on mammary gland tissues collected from cows during early, peak, and late lactation to determine miRNA expression profiles. Differentially expressed miRNA (miR-497) was selected for functional studies of fatty acid substitution. Simulants of miR-497 impaired fat metabolism [triacylglycerol (TAG) and cholesterol], whereas knockdown of miR-497 promoted fat metabolism in bovine mammary epithelial cells (BMECs) in vitro. In addition, in vitro experiments on BMECs showed that miR-497 could down-regulate C16:1, C17:1, C18:1, and C20:1 as well as long-chain polyunsaturated fats. Thus, these data expand the discovery of a critical role for miR-497 in mediating adipocyte differentiation. Through bioinformatics analysis and further validation, we identified large tumor suppressor kinase 1 (LATS1) as a target of miR-497. siRNA-LATS1 increased concentrations of fatty acids, TAG, and cholesterol in cells, indicating an active role of LATS1 in milk fat metabolism. In summary, miR-497/LATS1 can regulate the biological processes associated with TAG, cholesterol, and unsaturated fatty acid synthesis in cells, providing an experimental basis for further elucidating the mechanistic regulation of lipid metabolism in BMECs.

Comprehensive Approach to Medical Nutrition Therapy in Patients with Type 2 Diabetes Mellitus: From Diet to Bioactive Compounds.

In the pathogenesis of type 2 diabetes mellitus (T2DM), diet plays a key role. Individualized medical nutritional therapy, as part of lifestyle optimization, is one of the cornerstones for the management of T2DM and has been shown to improve metabolic outcomes. This paper discusses major aspects of the nutritional intervention (including macro- and micronutrients, nutraceuticals, and supplements), with key practical advice. Various eating patterns, such as the Mediterranean-style, low-carbohydrate, vegetarian or plant-based diets, as well as healthy eating plans with caloric deficits have been proven to have beneficial effects for patients with T2DM. So far, the evidence does not support a specific macronutrient distribution and meal plans should be individualized. Reducing the overall carbohydrate intake and replacing high glycemic index (GI) foods with low GI foods have been shown as valid options for patients with T2DM to improve glycemic control. Additionally, evidence supports the current recommendation to reduce the intake of free sugars to less than 10% of total energy intake, since their excessive intake promotes weight gain. The quality of fats seems to be rather important and the substitution of saturated and trans fatty acids with foods rich in monounsaturated and polyunsaturated fats lowers cardiovascular risk and improves glucose metabolism. There is no benefit of supplementation with antioxidants, such as carotene, vitamins E and C, or other micronutrients, due to the lack of consistent evidence showing efficacy and long-term safety. Some studies suggest possible beneficial metabolic effects of nutraceuticals in patients with T2DM, but more evidence about their efficacy and safety is still needed.

A Review of Low-Density Lipoprotein-Lowering Diets in the Age of Anti-Sense Technology.

This narrative review discusses an important issue, the primary role of diet in reducing low-density lipoprotein cholesterol (LDLc) concentrations in polygenic hypercholesterolemia. Two effective drugs, statins, and ezetimibe, that lower LDLc > 20% are relatively inexpensive and potential competitors to strict dieting. Biochemical and genomic studies have shown that proprotein convertase subtilisin kexin type 9 (PCSK9) plays an important role in low-density lipoprotein (LDL) and lipid metabolism. Clinical trials have demonstrated that inhibitory monoclonal antibodies of PCSK9 dose-dependently lower LDLc up to 60%, with evidence of both regression and stabilization of coronary atherosclerosis and a reduction in cardiovascular risk. Recent approaches using RNA interference to achieve PCSK9 inhibition are currently undergoing clinical evaluation. The latter presents an attractive option of twice-yearly injections. They are, however, currently expensive and unsuitable for moderate hypercholesterolemia, which is largely due to inappropriate patterns of eating. The best dietary approach, the substitution of saturated fatty acids by polyunsaturated fatty acids at 5% energy, yields > 10% lowering of LDLc. Foods such as nuts and brans, especially within a prudent, plant-based diet low in saturates complemented by supplements such as phytosterols, have the potential to reduce LDLc further. A combination of such foods has been shown to lower LDLc by 20%. A nutritional approach requires backing from industry to develop and market LDLc-lowering products before pharmacology replaces the diet option. Energetic support from health professionals is vital.

A Diet Enriched in Monounsaturated Fats Decreases Low Density Lipoprotein Concentrations in Cynomolgus Monkeys by a Different Mechanism than does a Diet Enriched in Polyunsaturated Fats

To determine the mechanisms whereby dietary fat saturation influences LDL cholesterol and apolipoprotein B concentrations, 10 cynomolgus monkeys were fed each of three experimental diets enriched in saturated, monounsaturated or polyunsaturated fatty acids in a crossover design consisting of three 13-wk periods. Each diet contained 30% of energy as fat with 0.05 mg cholesterol/kJ and differed solely by the isocaloric substitution of fatty acids as 60% of total fat energy. The replacement of dietary saturated fatty acids with either mono- or polyunsaturated fatty acids resulted in significant reductions of plasma total cholesterol (-17% and -30%, respectively), HDL cholesterol (-32% and -41%, respectively), apoA-1 (-37% and -44%, respectively), and apolipoprotein B (-28% and -36%, respectively) concentrations. Additionally, when dietary polyunsaturated fatty acids were substituted for saturated fatty acids, a 27% reduction in VLDL + LDL cholesterol was significant. Metabolic experiments suggested that the significantly reduced concentrations of apolipoprotein B observed during the monounsaturated and polyunsaturated fatty acid phases relative to the saturated fatty acid phase could not be entirely explained by changes in LDL apolipoprotein B clearance but rather were likely due to decreased LDL apolipoprotein B production rates. However, enhanced LDL apolipoprotein B catabolism accounted for the even greater reductions in VLDL + LDL cholesterol and apolipoprotein B concentrations observed during the polyunsaturated fatty acid phase vs. the monounsaturated fatty acid phase. Our data suggest that monounsaturated and polyunsaturated fatty acids lower apolipoprotein B concentrations by distinct mechanisms, with polyunsaturated fatty acids affecting LDL apolipoprotein B catabolism as well as production.

Fatty Acid Substitutions Modulate the Cytotoxicity of Puwainaphycins/Minutissamides Isolated from the Baltic Sea Cyanobacterium Nodularia harveyana UHCC-0300.

Puwainaphycins (PUW) and minutissamides (MIN) are structurally homologous cyclic lipopeptides that exhibit high structural variability and possess antifungal and cytotoxic activities. While only a minor variation can be found in the amino acid composition of the peptide cycle, the fatty acid (FA) moiety varies largely. The effect of FA functionalization on the bioactivity of PUW/MIN chemical variants is poorly understood. A rapid and selective liquid chromatography–mass spectrometry-based method led us to identify 13 PUW/MIN (1–13) chemical variants from the benthic cyanobacterium Nodularia harveyana strain UHCC-0300 from the Baltic Sea. Five new variants identified were designated as PUW H (1), PUW I (2), PUW J (4), PUW K (10), and PUW L (13) and varied slightly in the peptidic core composition, but a larger variation was observed in the oxo-, chloro-, and hydroxy-substitutions on the FA moiety. To address the effect of FA substitution on the cytotoxic effect, the major variants (3 and 5–11) together with four other PUW/MIN variants (14–17) previously isolated were included in the study. The data obtained showed that hydroxylation of the FA moiety abolishes the cytotoxicity or significantly reduces it when compared with the oxo-substituted C18-FA (compounds 5–8). The oxo-substitution had only a minor effect on the cytotoxicity of the compound when compared to variants bearing no substitution. The activity of PUW/MIN variants with chlorinated FA moieties varied depending on the position of the chlorine atom on the FA chain. This study also shows that variation in the amino acids distant from the FA moiety (position 4–8 of the peptide cycle) does not play an important role in determining the cytotoxicity of the compound. These findings confirmed that the lipophilicity of FA is essential to maintain the cytotoxicity of PUW/MIN lipopeptides. Further, a 63 kb puwainaphycin biosynthetic gene cluster from a draft genome of the N. harveyana strain UHCC-0300 was identified. This pathway encoded two specific lipoinitiation mechanisms as well as enzymes needed for the modification of the FA moiety. Examination on biosynthetic gene clusters and the structural variability of the produced PUW/MIN suggested different mechanisms of fatty-acyl-AMP ligase cooperation with accessory enzymes leading to a new set of PUW/MIN variants bearing differently substituted FA.

Functional Active Genomics of Isoprene Biogenesis and resistance to cardiovascular diseases

The pathologic development of the atherosclerotic process is often associated with the metabolism of saturated and unsaturated fatty acid. Substitution of the saturated fatty acids in nutrition for polyunsaturated fatty acids is traditionally associated with the lowering of risk of coronary breaches rise. Understanding the molecular mechanisms of the atherosclerosis development and progress is very important for early diagnostic and effective medical treatment of the above-mentioned disease. After a thorough analysis of the data available on the pathological atherosclerotic process, we have come to the conclusion that this disease begins from vascular smooth muscle cell (VSMC) impaired function. In the basis of the atherosclerosis development lies isoprenes biogenesis breach, caused by cholesterol and the products of its metabolism. Atherosclerosis is a chronic inflammatory disease of the media wall of large- and medium-sized arteries. And endothelium injury is a consequence of the pathologic process progressing in myocytes. Metabolic problems have become so relevant that it is time to form a metabolic policy. Real target programs for the prevention of the development of metabolic diseases and their diagnostics in the early stages of development should be developed. But in order to achieve this goal, it is necessary to know the real molecular mechanism of development of the early stages of metabolic diseases. It is necessary to recognize that the research work on the metabolic problem was carried out mainly in the plane of the functionally-energy parameter and captures only the consequences of the pathological process. And the very reason and early stages of metabolic diseases remained hidden from us, as they are depending on the pathology in the plane Regulatory, Information, Coordination and Functional active bioenergy system.

Prepubertal Dietary and Plasma Phospholipid Fatty Acids Related to Puberty Timing: Longitudinal Cohort and Mendelian Randomization Analyses.

Dietary intakes of polyunsaturated, monounsaturated and saturated fatty acids (FAs) have been inconsistently associated with puberty timing. We examined longitudinal associations of prepubertal dietary and plasma phospholipid FAs with several puberty timing traits in boys and girls. In the Avon Longitudinal Study of Parents and Children, prepubertal fat intakes at 3–7.5 years and plasma phospholipid FAs at 7.5 years were measured. Timings of Tanner stage 2 genital or breast development and voice breaking or menarche from repeated reports at 8–17 years, and age at peak height velocity (PHV) from repeated height measurements at 5–20 years were estimated. In linear regression models with adjustment for maternal and infant characteristics, dietary substitution of polyunsaturated FAs for saturated FAs, and higher concentrations of dihomo-γ-linolenic acid (20:3n6) and palmitoleic acid (16:1n7) were associated with earlier timing of puberty traits in girls (n = 3872) but not boys (n = 3654). In Mendelian Randomization models, higher genetically predicted circulating dihomo-γ-linolenic acid was associated with earlier menarche in girls. Based on repeated dietary intake data, objectively measured FAs and genetic causal inference, these findings suggest that dietary and endogenous metabolic pathways that increase plasma dihomo-γ-linolenic acid, an intermediate metabolite of n-6 polyunsaturated FAs, may promote earlier puberty timing in girls.

Contrasted central effects of n-3 versus n-6 diets on brain functions in diet-induced obesity in minipigs

ABSTRACT Introduction N3 polyunsaturated fatty acids (n-3 PUFAs) exert anti-inflammatory effects for the hypothalamus, but their extra-hypothalamic outcome lack documentation. We evaluated the central consequences of the substitution of saturated fatty acids with n-3 or n-6 PUFA in obesogenic diets. Methods Twenty-one miniature pigs were fed ad libitum obesogenic diets enriched in fat provided either as lard, fish oil (source for n-3 PUFAs), or sunflower oil (source for n-6 PUFAs) for ten weeks. The blood–brain barrier (BBB) permeability was quantified by CT perfusion. Central autonomic network was evaluated using heart rate variability, and PET 18FDG was performed to assess brain metabolism. Results BBB permeability was higher in lard group, but heart rate variability changed only in fish oil group. Brain connectivity analysis and voxel-based comparisons show regional differences between groups except for the cingulate cortex in fish oil vs. sunflower oil groups. Discussion : The minute changes in brain metabolism in obese pigs feed with fish oil compared with saturated fatty acids were sufficient to induce detrimental changes in heart rate variability. On the contrary, the BBB's decreased permeability in n-3 and n-6 PUFAs groups was protective against an obesity-driven damaged BBB.

Lack of glutathione peroxidase-8 in the ER impacts on lipid composition of HeLa cells microsomal membranes

GPx8 is a glutathione peroxidase homolog inserted in the membranes of endoplasmic reticulum (ER), where it seemingly plays a role in controlling redox status by preventing the spill of H2O2. We addressed the impact of GPx8 silencing on the lipidome of microsomal membranes, using stably GPx8-silenced HeLa cells. The two cell lines were clearly separated by Principal Component Analysis (PCA) and Partial Least Square Discriminant analysis (PLS-DA) of lipidome. Considering in detail the individual lipid classes, we observed that unsaturated glycerophospholipids (GPL) decreased, while only in phosphatidylinositols (PI) a substitution of monounsaturated fatty acids (MUFA) for polyunsaturated fatty acids (PUFA) was observed. Among sphingolipids (SL), ceramides (CER) decreased while sphingomyelins (SM) and neutral glycophingolipids (nGSL) increased. Here, in addition, longer chains than in controls in the amide fatty acid were present. The increase up to four folds of the CER (d18:1; c24:0) containing three hexose units, was the most remarkable species increasing in the differential lipidome of siGPx8 cells.Quantitative RT-PCR complied with lipidomic analysis specifically showing an increased expression of: i) acyl-CoA synthetase 5 (ACSL5); ii) CER synthase 2 and 4; iii) CER transporter (CERT); iv) UDP-glucosyl transferase (UDP-GlcT), associated to a decreased expression of UDP-galactosyl transferase (UDP-GalT). A role of the unfolded protein response (UPR) and the spliced form of the transcription factor XBP1 on the transcriptional changes of GPx8 silenced cells was ruled-out. Similarly, also the involvement of Nrf2 and NF-κB.Altogether our results indicate that GPx8-silencing of HeLa yields a membrane depleted by about 24% of polyunsaturated GPL and a corresponding increase of saturated or monounsaturated SM and specific nGSL. This is tentatively interpreted as an adaptive mechanism leading to an increased resistance to radical oxidations. Moreover, the marked shift of fatty acid composition of PI emerges as a possibly relevant issue in respect to the impact of GPx8 on signaling pathways.

Effects of Consumption of Various Fatty Acids on Serum HDL-Cholesterol Levels

Since HDL is an anti-atherogenic lipoprotein which plays a role in reversing cholesterol transport from the peripheral tissues to the liver, low HDL-cholesterol (HDL-C) levels are associated with the development of cardiovascular diseases. We previously studied effects of intake of various dietary fat on serum HDL-C levels to make “Dietary Reference Intakes for Japanese 2015”, and found that the substitution of fatty acids (FAs) for carbohydrates is beneficially associated with HDL-C, monounsaturated FA (MUFA) intake may not affect HDL-C and trans FA (TFA) is significantly associated with reduction of HDL-C. Consumption of n-3 poly-unsaturated FA (PUFA) was favorably associated with HDL-C. Here we review meta-analyses on the effects of various FA consumption on serum HDL-C levels, to make “Dietary Reference Intakes for Japanese 2020”. Consumption of ruminant-TFA may not affect HDL; however, increased industrially produced TFA intake was associated with a significant decrease in HDL and a significant increase in LDL. An intake of n-3 PUFA and MUFA was associated with an increase of HDL. An intake of saturated FA (SFA) was associated with an increase of HDL; however, SFA was also associated with an increase of LDL. J Endocrinol Metab. 2018;8(5):94-99 doi: https://doi.org/10.14740/jem534

Chilling injury is associated with changes in microsomal membrane lipids in guava fruit (Psidium guajava L.) and the use of controlled atmospheres reduce these effects

Abstract Storage of guava fruit cv ‘Media china’ at temperatures below 8 °C causes chilling injury associated with changes in cell membrane lipids. The aim of the present study was to evaluate the effects of two temperatures (4 and 10 °C) and three controlled atmospheres (air; 10 kPa O2; 5 kPa CO2 and 10 + 5 kPa of O2 and CO2) on microsomal lipid profiles in ripened fruit or fruit storage during three weeks. The study revealed that chilling injury is associated with a decrease in microsomal membrane volume and microsomal protein and phospholipids content (5%, 47% and 22%; respectively). Also, it was observed a decrease in Monogalactosyldiacylglycerol (MGDG), digalactosyldiacylglycerol (DGDG), Phosphatidylinositol (PI), phosphatidic acid (PA), cardiolipin (CL) contents and a substitution of saturated fatty acids (FA) for unsaturated FA in the microsomal membrane. Importantly, it was found that storing guava fruit 'Media China' at 10 °C under 5 kPa CO2 reduced chilling injury prevalence and increased shelf life, suggesting that these storage conditions maintained membrane functionality. Overall, these results indicate that CI is associated to deep alterations in membrane lipids pathway.

Fatty acid and quaternary ammonium modified chitosan nanoparticles for insulin delivery.

Liver is the major organ where insulin performs its physiological function. In this study, lauric acid and oleic acid were respectively conjugated to quaternized chitosan, and the fatty acid modified chitosan derivatives were used as the carriers to deliver the loaded insulin to liver. The nanoparticles with sizes of about 280 nm were fabricated via the electrostatic and hydrophobic interactions between insulin and the chitosan derivative. Both of insulin loading efficiency and loading capacity of the chitosan derivatives were higher than 98%. The surface hydrophobicity of the nanoparticles increased with the increases of fatty acid hydrophobicity and also fatty acid substitution degree of the chitosan derivative. The nanoparticles with higher surface hydrophobicity displayed higher hepatocyte absorption, more accumulation in the liver and better antidiabetic efficacy. Compared with free insulin treatment group, the relative pharmacological availabilities were 233% and 311% for the groups treated with the nanoparticles having lauric acid and oleic acid, respectively, after subcutaneous injection into diabetic mice. This study demonstrates that the nanoparticles fabricated from fatty acid modified polymer are an effective liver-targeted delivery system of insulin.

Dietary fats and cardiovascular health: a summary of the scientific evidence and current debate

This narrative review summarises the main studies of the role of the different fatty acids in coronary heart disease (CHD) and cardiovascular disease (CVD) risk and the current scientific debate on dietary recommendations. Reduction and substitution of the saturated fatty acids (SFAs) with the polyunsaturated fatty acids (PUFAs) are still the main dietary recommendation to prevent CHD and CVD. In the last few years, however, the strength of the scientific evidence underlying this dietary advice has been questioned. Recent investigations reappraise the previously declared deleterious role of the SFAs and reduce the positive role of PUFAs, mainly the omega-6, whereas the role of monounsaturated fatty acids (MUFAs) remains unclear. In contrast, the negative effects of trans fatty acids (TFAs) seem stronger than previously thought. Finally, criticisms have emerged from a dietary recommendation approach focussed on individual components rather than on wide food items and eating habits.

Effects of Consumption of Various Fatty Acids on Serum HDL-Cholesterol Levels

Since HDL is an anti-atherogenic lipoprotein which plays a role in reversing cholesterol transport from the peripheral tissues to the liver, low HDL-cholesterol (HDL-C) levels are associated with the development of cardiovascular diseases. We previously studied effects of intake of various dietary fat on serum HDL-C levels to make “Dietary Reference Intakes for Japanese 2015”, and found that the substitution of fatty acids (FAs) for carbohydrates is beneficially associated with HDL-C, monounsaturated FA (MUFA) intake may not affect HDL-C and trans FA (TFA) is significantly associated with reduction of HDL-C. Consumption of n-3 poly-unsaturated FA (PUFA) was favorably associated with HDL-C. Here we review meta-analyses on the effects of various FA consumption on serum HDL-C levels, to make “Dietary Reference Intakes for Japanese 2020”. Consumption of ruminant-TFA may not affect HDL; however, increased industrially produced TFA intake was associated with a significant decrease in HDL and a significant increase in LDL. An intake of n-3 PUFA and MUFA was associated with an increase of HDL. An intake of saturated FA (SFA) was associated with an increase of HDL; however, SFA was also associated with an increase of LDL. J Endocrinol Metab. 2018;8(5):94-99 doi: https://doi.org/10.14740/jem534

Structure-Activity Relationship of Plesiomonas shigelloides Lipid A to the Production of TNF-α, IL-1β, and IL-6 by Human and Murine Macrophages.

Plesiomonas shigelloides is a Gram-negative bacterium that is associated with diarrheal disease in humans. Lipopolysaccharide (LPS) is the main surface antigen and virulence factor of this bacterium. The lipid A (LA) moiety of LPS is the main region recognized by target cells of immune system. Here, we evaluated the biological activities of P. shigelloides LA for their abilities to induce the productions of proinflammatory cytokines (TNF-α, IL-1β, and IL-6) by human and murine macrophages [THP-1 macrophages and immortalized murine bone marrow-derived macrophages (iBMDM)]. Four native P. shigelloides LA preparations differing in their phosphoethanolamine (PEtn) substitution, length, number, and saturation of fatty acids were compared with Escherichia coli O55 LA. The bisphosphorylated, hexaacylated, and asymmetric forms of the P. shigelloides and E. coli LA molecules had similar activities in human and murine macrophages, indicating that shortening of the acyl chains in P. shigelloides LA had no effect on its in vitro activities. The PEtn decoration also had no impact on the interaction with the toll-like receptor 4/MD-2 receptor complex. The heptaacylated form of P. shigelloides LA decorated with 16:0 exhibited strong effect on proinflammatory activity, significantly decreasing the levels of all tested cytokines in both murine and human macrophages. Our results revealed that despite the presence of shorter acyl chains and an unsaturated acyl residue (16:1), the bisphosphorylated, hexaacylated, and asymmetric forms of P. shigelloides LA represent highly immunostimulatory structures.

Clinical Outcomes of Dietary Replacement of Saturated Fatty Acids with Unsaturated Fat Sources in Adults with Overweight and Obesity: A Systematic Review and Meta-Analysis of Randomized Control Trials

Background: Obesity and dyslipidemia are frequently treated with dietary interventions before pharmacotherapy is given. Diets high in unsaturated fat have proven advantageous to disease treatment. Aims: The purpose of this systematic review and meta-analysis was to assess the evidence of the effect of saturated fatty acids (SFA) replacement with unsaturated fatty acids (UFA) in metabolically healthy adults with overweight and obesity on markers of dyslipidemia and body composition. Methods: Keyword search was performed in PubMed, CINAHL, and Cochrane Library for randomized controlled trials (RCTs) evaluating the effects of fatty acid substitution in adults with overweight and obesity. Meta-analysis was performed on interventions assessing lipoprotein levels and body composition. Publication bias was assessed by funnel plot inspection, Begg's, and Egger's test. Results: Eight RCTs enrolling 663 participants were included in the review, with intervention durations between 4 and 28 weeks. Although nonsignificant (p = 0.06), meta-analysis found UFA replacement to reduce total cholesterol concentrations by 10.68 mg/dL (95%CI -21.90 to 0.53). Reductions in low-density lipoprotein cholesterol and triglycerides were statistically nonsignificant. Conclusions: Due to null results and a small number of studies included, there is no strong evidence that replacement of SFA with UFA may benefit lipid profiles in this population.

Effect of Dietary Intake of Saturated Fatty Acids on the Development of Atrial Fibrillation and the Effect of Replacement of Saturated With Monounsaturated and Polyunsaturated Fatty Acids

The aim of the present study was to explore substitution of intake of saturated fatty acids (FAs) with monounsaturated and polyunsaturated FAs and incident atrial fibrillation (AF) in men and women. A total of 57,053 Danish participants aged 50 to 64 years were enrolled in the Diet, Cancer and Health cohort study in 1993 to 1997 and completed a semiquantitative food frequency questionnaire at baseline. Follow-up was registry-based and data were analyzed using Cox proportional hazards regression. The statistical model was formulated in such a way that 1 g/day of saturated FAs was replaced with 1 g/day of monounsaturated or polyunsaturated FAs while keeping total fat intake, total energy intake, and energy intake from protein and carbohydrates constant. During a median follow-up of 17 years, 5,175 incident cases of AF occurred. In men, there was a higher hazard of AF when total n-3 polyunsaturated FAs replaced dietary saturated FAs-hazard ratio per 1-g substitution of FAs of 1.08 (95% confidence interval 1.02 to 1.14) in a model adjusted for lifestyle factors. For other substitutions of FAs (monounsaturated, total or n-6 polyunsaturated FAs), no consistent nor statistically significant associations were found. In conclusion, we found a moderately higher risk of AF in men, but not in women, when total n-3 polyunsaturated FAs replaced dietary saturated FAs. Substitution of saturated FAs with monounsaturated, total or n-6 polyunsaturated FAs was not associated with the risk of AF.

Linoleic acid causes greater weight gain than saturated fat without hypothalamic inflammation in the male mouse

A significant change in the Western diet, concurrent with the obesity epidemic, was a substitution of saturated fatty acids with polyunsaturated, specifically linoleic acid (LA). Despite increasing investigation on type as well as amount of fat, it is unclear which fatty acids are most obesogenic. The objective of this study was to determine the obesogenic potency of LA vs. saturated fatty acids and the involvement of hypothalamic inflammation. Forty-eight mice were divided into four groups: low-fat or three high-fat diets (HFDs, 45% kcals from fat) with LA comprising 1%, 15% and 22.5% of kilocalories, the balance being saturated fatty acids. Over 12 weeks, bodyweight, body composition, food intake, calorimetry, and glycemia assays were performed. Arcuate nucleus and blood were collected for mRNA and protein analysis. All HFD-fed mice were heavier and less glucose tolerant than control. The diet with 22.5% LA caused greater bodyweight gain, decreased activity, and insulin resistance compared to control and 1% LA. All HFDs elevated leptin and decreased ghrelin in plasma. Neuropeptides gene expression was higher in 22.5% HFD. The inflammatory gene Ikk was suppressed in 1% and 22.5% LA. No consistent pattern of inflammatory gene expression was observed, with suppression and augmentation of genes by one or all of the HFDs relative to control. These data indicate that, in male mice, LA induces obesity and insulin resistance and reduces activity more than saturated fat, supporting the hypothesis that increased LA intake may be a contributor to the obesity epidemic.