High Levels Of Free Fatty Acids Research Articles

Prognostic significance of pretreatment serum free fatty acid in patients with diffuse large B-cell lymphoma in the rituximab era: a retrospective analysis

BackgroundFatty acid metabolism is reportedly associated with various cancers. However, the role of pretreatment serum free fatty acid (FFA) levels in diffuse large B-cell lymphoma (DLBCL) prognosis is still unclear, and our study aimed to better elucidate its influence on clinical outcomes.MethodsThe medical records of 221 newly diagnosed DLBCL patients admitted to Fujian Medical University Union Hospital from January 2011 to December 2016 were analysed retrospectively. Receiver operating characteristic curve analysis was used to determine a cut-off value for pretreatment serum FFA levels for prognostic prediction in DLBCL patients. The relationship between pretreatment serum FFA levels and clinical and laboratory parameters was analysed. Univariate and multivariate analyses were used to assess prognostic factors for overall survival (OS) and progression-free survival (PFS).ResultsNewly diagnosed DLBCL patients with high pretreatment serum FFA levels (≥0.495 mmol/l) had more B symptoms, higher serum lactate dehydrogenase levels (> upper limit of normal), >1 extranodal site, and higher International Prognostic Index score (3–5) compared to those with low pretreatment serum FFA levels (<0.495 mmol/l). Higher serum FFA levels were independent prognostic factors for poor OS, but not PFS.ConclusionsHigh pretreatment serum FFA levels are associated with lower survival in untreated DLBCL patients.

C-reactive Protein, Free Fatty Acid, and Uric Acid as Predictors of Adverse Events after Endovascular Revascularization of Arterial Femoropopliteal Occlusion Lesions

This study aimed to investigate the relationship between pre-procedure high-sensitivity C-reactive protein (hsCRP), free fatty acid (FFA), and uric acid (UA) levels and post-procedure mortality and morbidity of endovascular revascularization of arterial femoropopliteal occlusion lesions. This was a retrospective review of clinical data retrieved from a prospectively held database in Peking Union Medical College Hospital. A total of 71 Patients who underwent endovascular treatment (EVT) for femoropopliteal occlusive disease between January 1, 2014 and November 1, 2017, were included in this study. Endpoints were defined as major adverse limb events (MALE; target vessel revascularization, amputation, or disease progression) and major adverse cardiovascular events (MACE; stroke, myocardial infarction, or all-cause death) during the entire follow-up period. Univariate and multivariate Cox proportional hazards regression models were used to evaluate the relationship of elevated biomarker levels (hsCRP, FFA and UA, measured by immunoturbidimetry assay, enzymatic assay and enzymatic assay, respectively) to MALE and MACE outcomes. Seventy-one patients (72 limbs) with sufficient follow-up information were included in the analysis. The mean age was 69.7 ± 8.6 years; 21.1% were female. The Rutherford class of target limbs were ≥ 3. The median follow-up was 36 (range 18-59 months). Univariate analyses revealed that patients with elevated hsCRP levels had an increased risk of MALE (hazard ratio [HR], 2.682; 95% confidence interval [CI], 1.281-5.617, P=0.009). High FFA levels were associated with an increased risk of MALE (HR, 2.658; 95% CI, 1.075-6.573; P=0.034). Multivariate analyses demonstrated that elevated hsCRP values (HR, 4.015; 95% CI, 1.628-10.551; P=0.003) and FFA value (HR, 3.034; 95% CI, 1.102-8.354; P=0.032) were both significantly associated with increased MALE. Elevated UA levels predicted MACE in the presence of confounders (HR, 11.446; 95% CI, 1.367-95.801 P=0.023). Pre-procedure hsCRP and FFA levels could serve as predictors of adverse events after EVT in patients with arterial femoropopliteal occlusive disease. The role of UA in MACE may warrant further investigation, because the correlation is not as powerful as the other two in the study.

Postpartum cows showed high oocyte triacylglycerols concurrently with high plasma free fatty acids

Impaired oocyte quality is one of the main causes of low fertility in modern high-yielding dairy cows. One of the potential factors of the impaired oocyte quality is the effects of free fatty acids (FFA). In fact, high FFA supplementation to culture media exacerbated oocyte developmental competence in vitro. Meanwhile, artificially induced high blood FFA levels in heifers did not affect the lipid composition of oocytes in vivo; however, the oocyte lipid profile of postpartum cows has not yet been investigated. Therefore, the profile of lipids involved in energy metabolism, including FFA and triacylglycerols (TAG), and their relationship between plasma and oocytes were compared among cows at different lactation stages. Heifers were used as a control group that was not affected by lactation. Plasma and oocytes were collected from heifers (n = 4) and 14 Holstein cows categorized to the early lactation stage: 25–47 days in milk (DIM) (n = 6), peak lactation stage: 61–65 DIM (n = 4), and middle lactation stage: 160–202 DIM (n = 4). The FFA and TAG profiles of plasma and oocytes were examined by liquid chromatography mass spectrometry. Plasma FFA positively correlated with oocyte TAG (P < 0.05). Plasma FFA and oocyte TAG were significantly higher in cows in the early lactation stage than in heifers (P < 0.05), while the peak and middle lactation stage groups had intermediate levels. The proportion of oleic acid in plasma increased concurrently with elevations in total FFA, while the compositions of oocyte FFA and TAG fatty acyls were constant regardless of plasma FFA concentration or oocyte TAG content. The present results suggest that high postpartum plasma FFA concentrations affect the quantity of oocyte TAG. Taken together with the adverse effects of high FFA concentrations on oocyte developmental competence in vitro, oocyte quality in postpartum cows may be impaired due to high circulating FFA concentrations. These results provide a more detailed understanding of the effects of postpartum high circulating FFA concentrations on the low fertility of cows.

TRIB3 regulates FSHR expression in human granulosa cells under high levels of free fatty acids

BackgroundGranulosa cells (GCs) in cumulus oophorus highly express follicle stimulating hormone receptor (FSHR), which is the most important mediator of both estradiol synthesis and oocyte maturation. Obese women have elevated free fatty acids (FFAs) levels in their follicular fluids and decreased FSHR expression in GCs, which is related to an altered protein kinase B/glycogen synthase kinase 3β (Akt/GSK3β) signaling pathway. Such FFA increases accompany 3-fold rises in pseudokinase 3 (TRIB3) expression and reduce the Akt phosphorylation status in both the human liver and in insulinoma cell lines. Therefore, in a high FFA environment, we determined if TRIB3 mediates regulation of FSHR via the Akt/GSK3β signaling pathway in human GCs.MethodsGCs from women undergoing in vitro fertilization were collected and designated as high and low FFAs cohorts based on their follicular fluid FFA content. GCs with low FFA levels and a human granulosa-like tumor (KGN) cell line were exposed to palmitic acid (PA), which is a dominate FFA follicular fluid constituent. The effects were assessed of this substitution on the Akt/GSK3β signaling pathway activity as well as the expressions of TRIB3 and FSHR at both the gene and protein levels by qPCR, Western blot and immunofluorescence staining analyses. Meanwhile, the individual effects of TRIB3 knockdown in KGN cells and p-AKT inhibitors were compared to determine the mechanisms of FFA-induced FSHR downregulation.ResultsThe average FSH dose consuming per oocyte (FSH dose/oocyte) was elevated and Top embryo quality ratio was decreased in women with high levels of FFAs in their follicular fluid. In these women, the GC TRIB3 and ATF4 protein expression levels were upregulated which was accompanied by FSHR downregulation. Such upregulation was confirmed based on corresponding increases in their gene expression levels. On the other hand, the levels of p-Akt decreased while p-GSK3β increased in the GCs. Moreover, TRIB3 knockdown reversed declines in FSHR expression and estradiol (E2) production in KGN cells treated with PA, which also resulted in increased p-Akt levels and declines in the p-GSK3β level. In contrast, treatment of TRIB3-knockdown cells with an inhibitor of p-Akt (Ser473) resulted in rises in the levels of both p-GSK3β as well as FSHR expression whereas E2 synthesis fell.ConclusionsDuring exposure to a high FFA content, TRIB3 can reduce FSHR expression through stimulation of the Akt/GSK3β pathway in human GCs. This response may contribute to inducing oocyte maturation.

Development and Clinical Translation of a Perioperative Nomogram Incorporating Free Fatty Acids to Predict Poor Outcome of Aneurysmal Subarachnoid Hemorrhage Following Endovascular Treatment

Objective: A reliable prediction of clinical outcome is important for clinicians to set appropriate medical strategies in treating patients with aneurysmal subarachnoid hemorrhage (aSAH). In this study, we aim to establish a perioperative nomogram involving serum lipid signatures for predicting poor outcomes at 3 months in patients with aSAH following endovascular therapy.Methods: Data of patients with aSAH receiving endovascular therapy were collected. Univariable and multivariable analyses were performed to screen independent predictors related to unfavorable outcomes defined by the modified Rankin Scale (mFS) ≥3. A novel nomogram based on these significant features was conducted. The clinical application of this nomogram was assessed by decision curve analysis (DCA) and clinical impact curve.Results: A total number of patients included in this study were 213 (average age 58.9 years, 65.7% female), representing a poor 3-month outcome rate of 48.8%. Free fatty acid (FFA) levels on admission were efficient in predicting poor outcomes compared with other contents in serum lipids. Univariable and multivariable analyses revealed advanced age (P = 0.034), poor Hunt Hess (HH) (odds ratio, OR = 3.7, P < 0.001) and mFS (OR = 6.0, P < 0.001), aneurysms in the posterior circulation (OR = 4.4, P = 0.019), and higher FFA levels on admission (OR = 3.1, P = 0.021) were negative independent predictors of poor 3 months outcome. A novel nomogram composed of these significant features presented a concordance index (C-index) of 0.831 while the practical benefit was validated by DCA and clinical impact curve. An online calculator based on R programming promoted the clinical application of this nomogram.Conclusion: Nomogram involving age, HH grade, mFS, aneurysm location, and serum FFA levels was sufficient to provide an individualized prediction of 3-month poor outcome for each patient with aSAH who underwent endovascular therapy.

Simulated In Vitro Infant Gastrointestinal Digestion of Infant Formulas Containing Different Fat Sources and Human Milk: Differences in Lipid Profiling and Free Fatty Acid Release.

Simulated in vitro infant gastrointestinal digestion of human milk and four infant formulas containing different fat sources was analyzed and compared in this study. Although there are disadvantages brought about by its larger droplet size than infant formulas, human milk exhibited a higher lipolysis level due to the presence of MFGM interfacial layers. Higher hydrolysis efficiency of infant formulas (IFB, IFC, and IFM) was due to the presence of MFGM/phospholipid-enriched materials. Human milk released higher free fatty acid levels, especially long-chain fatty acid, and less undigested TAG molecules at the end of digestion than infant formulas. Human milk had a higher proportion of MAG and DAG linked to long-chain fatty acid. Furthermore, several lipids were identified as potential biomarkers that could be used to further analyze differences in the biological properties of human, bovine, and caprine milk. This comprehensive analysis might be fruitful to formulate an infant formula closest to human milk.

Associations Between Serum Free Fatty Acid Levels and Incident Diabetes in a 3-Year Cohort Study.

PurposeHigh circulating free fatty acid (FFA) is associated with the development of diabetes. This study was designed to evaluate longitudinal associations between FFA levels, changes in FFA levels, and mean FFA levels and incident diabetes.Participants and MethodsThis 3-year cohort study was conducted in Ningyang between 2011 and 2014. Serum FFA, fasting blood glucose (FPG), 2-hour postprandial blood glucose (2hPG), and glycosylated hemoglobin (HbA1c) levels were measured at baseline and at the end of follow-up. A multivariate stepwise logistic regression model was used to evaluate associations between serum FFA levels in various groups and the risk of incident diabetes.ResultsOf the 2905 individuals without baseline diabetes, 290 developed diabetes by the 3-year follow-up. With increasing baseline FFA levels, the mean FPG, 2hPG, and HbA1c levels, and the prevalence of diabetes at the end of follow-up increased. The trend of FPG and HbA1c increase was not statistically significant. Higher baseline FFA levels were not significantly associated with greater risk of incident diabetes. However, longitudinal changes in serum FFA levels showed that individuals with serum FFA levels from normal to high (OR = 2.956, 95% CI: 2.089–4.184) or from high to high (OR = 3.343, 95% CI: 2.300–4.857) had greater risk of incident diabetes compared with those with normal to normal FFA levels. Similarly, individuals with ΔFFA ≥ 0 mmol/L (OR = 1.762, 95% CI: 1.373–2.262) or high mean serum FFA levels (OR = 2.120, 95% CI: 1.620–2.775) were at higher risk of incident diabetes than those with ΔFFA < 0 mmol/L or normal mean serum FFA levels.ConclusionThe longitudinal status of serum FFA levels, including chronic increases and sustained high levels, was more closely associated with high risk of incident diabetes than was high baseline FFA levels.

Soybean Oil Replacement by Palm Fatty Acid Distillate in Broiler Chicken Diets: Fat Digestibility and Lipid-Class Content along the Intestinal Tract.

Simple SummaryPalm fatty acid distillate is a by-product of palm oil refining. It is of both environmental and economic interest to include it in the diets of broiler chickens. However, its high saturation degree and acidity level limit its use. This study aimed to assess the effect of replacing soybean oil with increasing levels of palm fatty acid distillate on the utilization of fat by broilers. Dietary fat hydrolysis was mostly affected by the age of the bird and including palm fatty acid distillate mainly affected the absorption process. The replacement of soybean oil by palm fatty acid distillate reduced the total fat utilization, and in starter chicks delayed the site of fatty acid absorption. As the age increased, the digestibility of saturated fatty acids improved, and, above all, it improved the free fatty acid utilization. Therefore, the potential inclusion of palm fatty acid distillate for broiler feeds depends on the age of the bird. It would not be recommended to include this by-product in starter feeds. However, for the grower-finisher phase, blending palm fatty acid distillate with soybean oil (1:3, w/w) could be a suitable alternative, that does not have negative repercussions for either fatty acid absorption or growth performance.Palm fatty acid distillate (PFAD) is a by-product of palm oil (P) refining. Its use in chicken diets is a way to reduce the cost of feed and the environmental impact. Its low unsaturated:saturated fatty acid ratio (UFA:SFA) and its high free fatty acid (FFA) level could be partially counteracted by its blending with soybean oil (S). The objective was to assess the effect of replacing S with different levels of PFAD on lipid-class content and fatty acid (FA) digestibility along the intestinal tract and in the excreta of 11 and 35-day-old broiler chickens. Five experimental diets were prepared by supplementing a basal diet with S (S6), PFAD (PA6), two blends of them (S4-PA2 and S2-PA4), or P (P6) at 6%. Replacing S with PFAD did not affect performance parameters (p > 0.05) but negatively affected feed AME, FA digestibility, and FFA intestinal content (p < 0.05), especially in starter chicks. Including PFAD delayed total FA (TFA) absorption (p < 0.05) at 11 days, but at 35 days it did not affect the TFA absorption rate. The use of PFAD blended with S, when FFA ≤ 30% and UFA:SFA ≥ 2.6, led to adequate energy utilization in broiler grower-finisher diets.

Computational Hypothesis: How Intra-Hepatic Functional Heterogeneity May Influence the Cascading Progression of Free Fatty Acid-Induced Non-Alcoholic Fatty Liver Disease (NAFLD).

Non-Alcoholic Fatty Liver Disease (NAFLD) is the most common type of chronic liver disease in developed nations, affecting around 25% of the population. Elucidating the factors causing NAFLD in individual patients to progress in different rates and to different degrees of severity, is a matter of active medical research. Here, we aim to provide evidence that the intra-hepatic heterogeneity of rheological, metabolic and tissue-regenerating capacities plays a central role in disease progression. We developed a generic mathematical model that constitutes the liver as ensemble of small liver units differing in their capacities to metabolize potentially cytotoxic free fatty acids (FFAs) and to repair FFA-induced cell damage. Transition from simple steatosis to more severe forms of NAFLD is described as self-amplifying process of cascading liver failure, which, to stop, depends essentially on the distribution of functional capacities across the liver. Model simulations provided the following insights: (1) A persistently high plasma level of FFAs is sufficient to drive the liver through different stages of NAFLD; (2) Presence of NAFLD amplifies the deleterious impact of additional tissue-damaging hits; and (3) Coexistence of non-steatotic and highly steatotic regions is indicative for the later occurrence of severe NAFLD stages.

Pre-esterification of high acidity animal fats to produce biodiesel: A kinetic study

Biodiesel is generally produced through transesterification with base catalysts, using vegetable oils as raw materials. These vegetable oils can be expensive, being replaced for other alternatives like animal fats. However, animal fats usually present high free fatty acid (FFA) levels, which make the use of base catalysts difficult. Pre-esterification of these raw materials is an effective pre-treatment to reduce FFA levels as free fatty acids react with methanol to produce methyl esters and water. In this research work, the esterification of animal fats was studied, obtaining kinetic parameters through a simplified model. This model, with 1.5 reaction order with respect to FFA, only takes into account the direct reaction of esterification chemical equilibrium, proving that the reaction rate of the inverse reaction is negligible. The reaction rate coefficient, which presents a linear correlation between methanol and the catalyst (H2SO4), was adjusted to temperature through the Arrhenius equation, obtaining the activation energy and the pre-exponential factor. A thorough experimentation has been carried out in order to determine the influence of catalyst concentration, methanol/fat ratio and reaction times corresponding to esterification and transesterification. Reaction times for esterification and transesterification longer than 120 min were enough to obtain biodiesel yields above 97%.

The Effect of Energy Metabolism up to the Peak of Lactation on the Main Fractions of Fatty Acids in the Milk of Selected Dairy Cow Breeds.

Simple SummaryThe metabolism of cows up to the peak of lactation significantly influences production parameters and the quality of the production cycle. The aim of this study was to analyze the energy metabolism of selected breed groups of cows and its variability in different stages of early lactation. The analysis was performed using data on the following parameters: body condition score (BCS), fatty acid (FA) fractions, basic milk constituents, and serum parameters (BHBA, glucose, and leptin). Holstein-Friesian (HF) cows and HF crossbreds with Black-and-White Lowland (BW) bulls generally had higher daily yields and reached the peak of lactation earlier. These cows, however, suffered the greatest loss in BCS, which led to higher levels of non-esterified fatty acid (NEFA) in the blood than in the other groups. Cows entering the peak of lactation with less intensive production were shown to have lower levels of leptin and higher glucose concentrations in the blood. The smaller loss of BCS in these cows did not lead to rapid lipolysis, and therefore the release of large amounts of non-esterified fatty acids and β-hydroxybutyrate into the blood was limited. The milk of breed groups that had somewhat lower yield and reached the peak of lactation about 11 days later (Simmental and Black-and-White Lowland) had a more beneficial fatty acid profile and casein content. The results indicate that one of the important factors influencing the intensity of lipolysis is leptin, which regulates appetite. The Simmental and Black-and-White Lowland groups had lower concentrations of leptin. This suggests the need for further research on how appetite and the prolongation of feed intake is linked to longer availability of nutrients, including glucose.During early lactation in dairy cows, metabolic processes are adopted to provide energy and nutrients for the synthesis of milk compounds. High milk production potential includes sudden changes in energy metabolism (negative energy balance (NEB)) that can induce uncontrolled lipomobilization and high blood free fatty acid (FFA) levels. Destabilization of cows’ energy may interfere with endocrine homeostasis, such as the secretion of leptin, a co-regulator of the appetite center. Therefore, it is important to analyze the physiological aspects of the maintenance of energy homeostasis in various dairy breeds. Usually it is crucial for the health of cows, influences the production cycle and lifetime yield, and determines the profitability of production and milk quality. The aim of this study was to analyze the energy metabolism of selected breed groups of cows and its variability in different stages of early lactation. The analysis was performed using data on the following parameters: body condition score (BCS), fatty acid (FA) fractions, basic milk constituents, and serum parameters (BHBA, glucose, and leptin). These results were analyzed in relation to parameters of energy metabolism during the stage up to the peak of lactation. An earlier peak of lactation was shown to be conducive to an increase in the content of non-esterified fatty acids (NEFAs) and of casein and κ-casein. During the study period, parameters characterizing the maintenance of energy homeostasis were usually lower in the Simmental and Black-and-White Lowland cows. Compared to the group with the highest production, their yield was from 2.8 to 4.7 kg lower, but the milk had a more beneficial fatty acid profile and nutrient content, determining suitability for cheese making. At the same time, they had lower levels of NEFAs and β-hydroxybutyrate in the blood, which indicates less spontaneous lipolysis of fat reserves. Concentrations of the appetite regulator leptin in the blood were correlated negatively (p ≤ 0.05) with the glucose concentration (–0.259) and positively with NEFA (0.416). The level of NEFAs was at the same time positively correlated with the content of saturated fatty acids in the milk (0.282–0.652; p ≤ 0.05). These results contribute to our knowledge of the effect of production intensity on the maintenance of homeostasis up to the peak of lactation in dairy breeds with differing production potential. In practice, this may increase the possibilities of improving milk quality and the profitability of production.

Pancreatic β cells control glucose homeostasis via the secretion of exosomal miR-29 family.

Secreted microRNAs (miRNAs) are novel endocrine factors that play essential pathological and physiological roles. Here, we report that pancreatic β cell‐released exosomal miR‐29 family members (miR‐29s) regulate hepatic insulin sensitivity and control glucose homeostasis. Cultured pancreatic islets were shown to secrete miR‐29s in response to high levels of free fatty acids (FFAs) in vitro. In vivo, high levels of FFAs, promoted by either high‐fat diet (HFD) feeding (physiopathological) or fasting (physiological), increased the secretion of miR‐29s into plasma. Intravenous administration of exosomal miR‐29s attenuated insulin sensitivity. The overexpression of miR‐29s in the β cells of transgenic (TG) mice promoted the secretion of miR‐29s and inhibited the insulin‐mediated suppression of glucose output in the liver. We used selective overexpression of traceable heterogenous mutant miR‐29s in β cells to confirm that islet‐derived exosomal miR‐29s target insulin signalling in the liver and blunt hepatic insulin sensitivity. Moreover, in vivo disruption of miR‐29s expression in β cells reversed HFD‐induced insulin resistance. In vitro experiments demonstrated that isolated exosomes enriched in miR‐29s inhibited insulin signalling in the liver and increased hepatic glucose production. These results unveil a novel β cell‐derived secretory signal—exosomal miR‐29s—and provide insight into the roles of miR‐29s in manipulating glucose homeostasis.

Influence of Industrial Processing on Physiochemical Characteristics of Soybean Oil and Deodorizer Distillates

The present study aimed to evaluate the impact of industrial processing (neutralization/degumming, bleaching, and deodorization) on physicochemical characteristics of soybean oil and soybean oil deodorizer distillate (SBO-DD) collected from two different industries. The substantial impact of processing was observed on all physicochemical parameters except the iodine value (IV) and saponification value (SV). Gas chromatography-flame ionization detector (GC-FID) and Gas chromatography-mass spectrometry (GC-MS) analytical techniques were used for the quantification of individual fatty acids, sterols, and 3-monochloropropane diol (3-MCPD) ester. Among the fatty acids, palmitic and linoleic acids were present at higher concentrations in all processing stages. Among sterols, β-sitosterol was found to be higher (25.65 and#181;g/g) in crude soybean oil and reduced to 16.44 and#181;g/g after processing till the final deodorization stage. 3-MCPD ester was developed during the neutralization/degumming process and further increased during bleaching and deodorization up to 315 and#181;g/kg, respectively. SBO-DD was found to be a rich source of total and individual sterols as compared to crude or processed soybean oil. High free fatty acid (FFA) level in deodorizer distillate indicated that SBO-DD is a potential source of biodiesel production.

Influence of Industrial Processing on Physiochemical Characteristics of Soybean Oil and Deodorizer Distillates

The present study aimed to evaluate the impact of industrial processing (neutralization/degumming, bleaching, and deodorization) on physicochemical characteristics of soybean oil and soybean oil deodorizer distillate (SBO-DD) collected from two different industries. The substantial impact of processing was observed on all physicochemical parameters except the iodine value (IV) and saponification value (SV). Gas chromatography-flame ionization detector (GC-FID) and Gas chromatography-mass spectrometry (GC-MS) analytical techniques were used for the quantification of individual fatty acids, sterols, and 3-monochloropropane diol (3-MCPD) ester. Among the fatty acids, palmitic and linoleic acids were present at higher concentrations in all processing stages. Among sterols, β-sitosterol was found to be higher (25.65 and#181;g/g) in crude soybean oil and reduced to 16.44 and#181;g/g after processing till the final deodorization stage. 3-MCPD ester was developed during the neutralization/degumming process and further increased during bleaching and deodorization up to 315 and#181;g/kg, respectively. SBO-DD was found to be a rich source of total and individual sterols as compared to crude or processed soybean oil. High free fatty acid (FFA) level in deodorizer distillate indicated that SBO-DD is a potential source of biodiesel production.

Association of plasma free fatty acids levels with the presence and severity of coronary and carotid atherosclerotic plaque in patients with type 2 diabetes mellitus

BackgroundPrevious studies have suggested that patients with diabetes mellitus (DM) have higher prevalence of atherosclerotic cardiovascular disease (ASCVD), and plasma levels of free fatty acids (FFAs) are a useful marker for predicting ASCVD. We hypothesized that FFAs could predict both coronary and carotid lesions in an individual with type 2 DM (T2DM). The present study, hence, was to investigate the relation of plasma FFA level to the presence and severity of coronary and carotid atherosclerosis in patients with T2DM.MethodsThree hundred and two consecutive individuals with T2DM who have received carotid ultrasonography and coronary angiography due to chest pain were enrolled in this study. Plasma FFAs were measured using an automatic biochemistry analyzer. Coronary and carotid severity was evaluated by Gensini score and Crouse score respectively. Subsequently, the relation of FFA levels to the presence and severity of coronary artery disease (CAD) and carotid atherosclerotic plaque (CAP) in whole individuals were also assessed.ResultsIncreased plasma FFA levels were found in the groups either CAD or CAP compared to those without. Patients with higher level of FFAs had a higher CAD (89.9%) and elevated prevalence of CAP (69.7%). And also, patients with higher level of FFAs had a higher Gensini and Crouse scores. Multivariate regression analysis showed that FFA levels were independently associated with the presence of CAD and CAP (OR = 1.83, 95%CI: 1.27–2.65, P = 0.001; OR = 1.62, 95%CI: 1.22–2.14, P = 0.001, respectively). The area under the curve (AUC) was 0.68 and 0.65 for predicting the presence of CAD and CAP in patients with DM respectively.ConclusionsThe present study firstly indicated that elevated FFA levels appeared associated with both the presence and severity of CAD and CAP in patients with T2DM, suggesting that plasma FFA levels may be a useful biomarker for improving management of patients with T2DM.

Predictive value of free fatty acid levels in embolic stroke of undetermined source: A retrospective observational study.

The present study aimed to investigate the predictive value of free fatty acid (FFA) in embolic stroke of undetermined source (ESUS) according to the presence of potential embolic sources (PES) after extensive etiologic evaluation.This was a retrospective observational study based on a single-center registry from January 2011 to July 2017. Stroke subtypes were determined through laboratory findings, brain, and angiographic imaging, carotid ultrasonography, transthoracic echocardiography, and 24-hour Holter monitoring. If ESUS was suspected, transesophageal echocardiography was additionally performed. Patients were classified into ESUS with PES and ESUS without PES. PES included mitral annular calcification, mitral valve prolapse, patent foramen ovale, atrial septal aneurysm, spontaneous echo contrast, ventricular aneurysm, and high-risk plaques of aortic arch, or carotid bulb. We compared clinical and laboratory findings between the two groups.Of a total of 110 ESUS patients, 61 patients (55.5%) had no PES. Patients with ESUS without PES had higher levels of serum FFA, systolic blood pressure, diastolic blood pressure (DBP), and left atrial (LA) enlargement compared with those of ESUS with PES. Multivariable analysis demonstrated that the FFA level, DBP, and LA volume index were associated with ESUS without PES [odds ratio (OR) 1.038, 95% confidence interval (CI) 1.019–1.058 for FFA/10 μEq/L, OR 1.414, 95% CI 1.037–1.928 for DBP/10 mm Hg, and OR 1.073, 95% CI 1.009–1.141 for LA volume index].Higher levels of FFA, DBP, and LA volume index are associated with ESUS without PES, highlighting the need to identify the role of these markers in ESUS through further large-scale, multi-center and prospective studies.

Loss of Caveolin-1 Is Associated with a Decrease in Beta Cell Death in Mice on a High Fat Diet.

Elevated free fatty acids (FFAs) impair beta cell function and reduce beta cell mass as a consequence of the lipotoxicity that occurs in type 2 diabetes (T2D). We previously reported that the membrane protein caveolin-1 (CAV1) sensitizes to palmitate-induced apoptosis in the beta pancreatic cell line MIN6. Thus, our hypothesis was that CAV1 knock-out (CAV1 KO) mice subjected to a high fat diet (HFD) should suffer less damage to beta cells than wild type (WT) mice. Here, we evaluated the in vivo response of beta cells in the pancreatic islets of 8-week-old C57Bl/6J CAV1 KO mice subjected to a control diet (CD, 14% kcal fat) or a HFD (60% kcal fat) for 12 weeks. We observed that CAV1 KO mice were resistant to weight gain when on HFD, although they had high serum cholesterol and FFA levels, impaired glucose tolerance and were insulin resistant. Some of these alterations were also observed in mice on CD. Interestingly, KO mice fed with HFD showed an adaptive response of the pancreatic beta cells and exhibited a significant decrease in beta cell apoptosis in their islets compared to WT mice. These in vivo results suggest that although the CAV1 KO mice are metabolically unhealthy, they adapt better to a HFD than WT mice. To shed light on the possible signaling pathway(s) involved, MIN6 murine beta cells expressing (MIN6 CAV) or not expressing (MIN6 Mock) CAV1 were incubated with the saturated fatty acid palmitate in the presence of mitogen-activated protein kinase inhibitors. Western blot analysis revealed that CAV1 enhanced palmitate-induced JNK, p38 and ERK phosphorylation in MIN6 CAV1 cells. Moreover, all the MAPK inhibitors partially restored MIN6 viability, but the effect was most notable with the ERK inhibitor. In conclusion, our results suggest that CAV1 KO mice adapted better to a HFD despite their altered metabolic state and that this may at least in part be due to reduced beta cell damage. Moreover, they indicate that the ability of CAV1 to increase sensitivity to FFAs may be mediated by MAPK and particularly ERK activation.

1751-P: Induction of Sirt1-AMPK Pathway by GLP-1RA Liraglutide Reduces Hepatic Lipid Accumulation and Insulin Resistance

Hepatic insulin resistance is associated with metabolic disorders such as type 2 diabetes (T2D), which often develops after the accumulation of lipids in the liver. In particular, elevated plasma levels of free fatty acids (FFA) are the primary sources of hepatic lipid accumulation that contributes to the development of insulin-resistant states. Interestingly, one gut-derived incretin hormone receptor called glucagon-like peptide 1 (GLP-1) receptor, is highly expressed on human hepatocytes. Although GLP-1-based therapies have shown great benefit in the treatment of T2D with improved glycemic control, they also additionally possess extrapancreatic metabolic actions including that in the liver. Studies have demonstrated that GLP-1 receptor agonist (GLP-1 RA) may reverse the progression of nonalcoholic fatty liver disease (NAFLD), a T2D-related disorder characterized by hepatic lipid accumulation. This suggests GLP-1 RA may be effective treatment options for NAFLD and associated hepatic disorders, but the mechanism behind this is still unknown. In the present study, we investigated the function of GLP-1 signaling in protecting human HepG2 hepatocytes from FFA-related damages. By using high-content analysis (HCA) cellomics techniques, we found that treatment with the GLP-1 RA liraglutide has shown a significant lipid droplets-lowering effect in hepatocytes exposure to high levels of FFAs. Liraglutide also decreased free radical generation and subsequently reduced oxidative stress, thus alleviated FFA induced inflammation. Moreover, activation of AMPK by liraglutide increased insulin sensitivity and improved oxidative stress-induced senescence by inducing Sirt1 pathway. Collectively, our results demonstrated that hepatic GLP-1 signaling may play a crucial role in the regulation of lipid deposits and related disorders in liver. This suggests the potential therapeutic usage of GLP-1 RA-based strategies for patients with T2D who also have NAFLD. Disclosure C. Huang: None. H. Li: None. C. Peng: None. E. Kornelius: None. Y. Yang: None. L. Chiu: None. C. Lin: None. Funding Ministry of Science and Technology of Taiwan (108-2314-B-040-021-MY3)

Crude Palm Oil Product Quality Control Using Seven Tools (case study: XYZ Company)

Competition in the palm oil processing industry in Indonesia is very competitive. One of the factors that influence the good name of the company is the quality of the product produced. PT. XYZ is a palm oil processing factory with export and domestic market share. In order for the company to be able to compete with other companies engaged in similar industries, the company is required to need to carry out strict checks on product quality. PT. XYZ faces several obstacles to meet the quality standards of its main products namely Crude Palm Oil (CPO). The problem that is often found related to quality in CPO is the quality of CPO that does not meet consumer standards even though the company has implemented quality control in CPO production. This can reduce consumer confidence in the products sold by the company. CPO product quality standards set are free fatty acid levels (FFA) (<5%), water content (<0.15%) and impurities content (<0.02%). This study aims to determine what types of defect affect the quality of CPO and what causes the defect. This research uses seven tools method consisting of stratification, check sheet, histogram, pareto diagram, scatter diagram, control chart and cause and effect diagram. From the results of the Pareto diagram analysis it appears that the dominant defect that occurs in CPO is high free fatty acid levels with a percentage of 39.3%, then followed by defect with high impurities content of 35.4% and high water content of 25.3%. By using the Pareto 80/20 principle, the defect factor which is further analyzed is the defect of high free fatty acids and high levels of impurities. Through scatter diagrams and correlation analysis, the value of r = 0.5, where the value indicates that high free fatty acid defects and high impurities have a positive effect on the number of defects. By using a causal diagram analysis (fishbone diagram) it was found that the factors causing the high level of damage to this palm oil product are influenced by 3 main factors, namely raw materials, humans, and machinery.

Late-dropping macadamia nuts have reduced shelf life

The quality of tree nuts can be influenced by their harvest time, cultivar and seasonal growing conditions. Some macadamia cultivars retain mature nuts in the tree for several months before fruit abscission and this can result in variations in harvest time. It is not known how the variations in harvest time affect the quality and shelf life of macadamia cultivars. We investigated how harvest time and cultivar influence the quality and shelf life of macadamia kernels. We tested the shelf life of kernels using two techniques: (1) a long-term shelf-life method; and (2) a short-term accelerated-aging method that assessed oxidative stability based on hexanal concentrations. Cultivars HAES 344 (344) and Hidden Valley A16 (A16) were harvested in May and late-abscising nuts of cultivar A16 were also harvested in September. Peroxide values, free fatty acid levels and fatty acid composition of kernels in the long-term experiment were measured after 0, 6, 12, 15 and 18 months of storage at 25 °C. Kernels in the short-term accelerated aging experiment were incubated at 45 °C, and hexanal concentrations were measured before incubation and after 6, 12 and 18 days. Kernels from late-abscising nuts (September) had much higher free fatty acid levels after 18 months of storage than kernels from early-harvested nuts (May). Cultivar A16 (September) kernels had significantly higher hexanal concentrations than cultivar 344 (May) and A16 (September) kernels at 12 and 18 days of incubation. The accelerated aging technique could detect differences in oxidative stability between different batches. Nuts harvested in September had shorter shelf life by about 3–6 months than those harvested in May, based on both predicted shelf life and actual time taken to reach acceptable-quality limits. Therefore, we recommend harvesting macadamia nuts as soon as possible after maturity to minimise quality losses.