High Levels Of Free Fatty Acids Research Articles

The association of preoperative serum free fatty acid levels with survival in breast cancer patients

Background and objectivesSerum free fatty acids (FFA) are associated with various types of cancer. However, the prognostic value of preoperative serum FFA levels and breast cancer (BC) remains unclear. This study aimed to elucidate the specific relationship between FFA levels and BC outcomes.MethodsA retrospective review was conducted on 4133 patients with BC admitted to Sun Yat-sen Memorial Hospital from January 2015 to October 2021. Preoperative serum FFA levels were detected by the enzymatic endpoint method. The relationship between serum FFA levels and clinical characteristics was analyzed based on FFA interquartile range. Restricted cubic splines and multivariate Cox regression analyses were used to assess the relationship between preoperative serum FFA levels and overall survival (OS) in patients with BC. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated.ResultsAccording to the FFA interquartile range, FFA levels were significantly correlated with OS (years) (p < 0.001). Restricted cubic spline analysis might reveal a U-shaped relationship between preoperative serum FFA levels and OS, after adjusting for other variables. According to the cutoff points for FFAs, multivariate Cox regression analyses showed that patients with low FFA levels (≤ 250 µmol/L) had higher rates of all-cause mortality and cancer-specific mortality than those with high FFA levels (530–700 µmol/L) in the total population and patients with a BMI of 18.5–24.0 kg/m2. A trend was observed indicating that elevated FFA levels (≥ 715 µmol/L) were associated with worse prognosis; however, this association failed to reach statistical significance.ConclusionsThere might be a nonlinear U-shaped relationship between preoperative serum FFA levels and survival in breast cancer patients, with lower FFA levels associated with worse OS. The effect of elevated FFA levels on prognosis requires further investigation.

Farm factors associated with increased free fatty acids in bulk tank milk

Elevated concentrations of free fatty acids (FFA) in bulk tank milk are a milk quality concern in the dairy industry. Hydrolysis of triacylglycerols (TAG) yields FFA, and milk with ≥ 1.20 mmol FFA/ 100 g of milk fat is associated with undesirable characteristics, such as off-flavor, rancidity, reduced foam stability, and inhibited cheese-milk coagulation. Research on FFA is limited and absent in North America, but research out of European regions indicates that high FFA are multifactorial. This study aimed to identify farm-level FFA risk factors in Canadian dairy herds. A cross-sectional study was conducted on 293 Canadian dairy farms in Ontario (n = 238) and British Columbia (n = 55). Over 2 years, selected farms were visited once to complete a survey, assess milking systems, and gather data on the diet of lactating cows. Bulk tank FFA values for each farm 15 d before and 15 d after the research visit were obtained from the corresponding province's milk marketing board. Using these values, a monthly FFA average was calculated for each farm and used as the outcome variable. Seventy-one farms were tie stall, 109 were free-stall with milking parlors, and 113 were free-stall with automated milking systems (AMS). The mean bulk tank FFA was 0.84 mmol/ 100 g of fat (SD = 0.40, range 0.26 to 3.67), and 10% (n = 29) of herds had an elevated monthly average FFA (≥1.20 mmol/ 100 g of fat). In the final multivariable linear regression model, milking frequency ≥3x/d (times per day) compared with <3x/d was associated with a greater FFA concentration in AMS (β = 0.27, 95% CI: 0.12, 0.41) and tie stall milking systems (β = 1.17, 95% CI: 0.76-1.59). Regardless of milking frequency, none of the parlor farms visited had FFA ≥1.20 mmol/ 100 g of fat. For farms milking ≥3x/d, not changing the milk filter at least 2x/d was associated with greater FFA concentrations (β = 0.27, 95% CI: 0.10, 0.44). The absence of pre-cooling was also associated with higher FFA levels (β = 0.16, 95% CI: 0.02, 0.3). The final model adjusted R2 of 29% indicates that more factors associated with bulk tank milk FFA still need to be identified, which may include seasonal, milk composition, and individual cow factors.

Metabolic and Inflammatory Profiles in Children and Adolescents with Autism Spectrum Disorder: A Cross-Sectional Study

Background/Objectives: Autism spectrum disorder (ASD) is associated with several coexisting diseases or comorbidities, including inflammatory and metabolic disorders. In fact, ASD symptoms may be associated with immune system dysfunction. However, studies investigating the peripheral blood levels of immune cells are lacking and have provided mixed findings. In this study, we evaluated the relationship between the intensity level of ASD symptoms and the inflammatory and metabolic profiles in 154 children and adolescents (2–17 years). Methods: Bayesian multilevel models were used to examine the relationship between their symptom intensities and inflammatory/metabolic profiles. Results: Heavier children had higher values for triglyceride and insulin levels. Children with a level 3 of ASD intensity had higher free fatty acids levels. However, when adjusting for ASD intensity, gender, medication use, or weight status, older children appeared to have higher values of triglycerides, insulin levels, and free fatty acids. Conclusions: We concluded that as Brazilian children with ASD became older, they had a higher risk for insulin resistance.

Adipose tissue insulin resistance in young Japanese women is associated with metabolic abnormalities and dehydroepiandrosterone-sulfate.

The proportion of young Japanese women who are underweight is exceptionally high. We previously showed that the prevalence of impaired glucose tolerance (IGT) was high in underweight young Japanese women, and that IGT was characterized by high free fatty acid levels and adipose tissue insulin resistance (ATIR). As the next step, this study aimed to explore factors associated with elevated ATIR in this population. Ninety-eight young, healthy, underweight women participated in this study. To investigate the relationship between ATIR and metabolic parameters, participants were divided into three groups (Low, Medium, and High) according to ATIR level. Body composition examination, oral glucose tolerance testing, and blood biochemical analysis were performed; Adipo-IR and the Matsuda index were used as indices of ATIR and systemic insulin sensitivity, respectively. Participants in the High ATIR group had the highest prevalence of IGT (25%), and significantly higher body fat percentage, whole-body insulin resistance, and levels of insulin-like growth factor-1 and dehydroepiandrosterone sulfate (DHEA-S) than the other two groups. They were also significantly younger and had higher systolic blood pressure than the Low ATIR group. Multiple regression analysis showed that DHEA-S, which is known to enhance lipolysis in adipose tissue, was an independent correlate of ATIR. Underweight Japanese women with high ATIR had impaired metabolism, a higher prevalence of IGT, higher systemic insulin resistance, and higher systolic blood pressure. DHEA-S was a determinant of high ATIR levels.

The U -shape relationship between free fatty acid level and adverse outcomes in coronary artery disease patients with hypertension: evidence from a large prospective cohort study

BackgroundEvidence is scarce on the effect of free fatty acid (FFA) level in the prognosis of coronary artery disease (CAD) patients with hypertension. This study.MethodsA large prospective cohort study with a follow-up period of average 2 years was conducted at Xinjiang Medical University Affiliated First Hospital from December 2016 to October 2021. A total of 10,395 CAD participants were divided into groups based on FFA concentration and hypertension status, and then primary outcome mortality and secondary endpoint ischemic events were assessed in the different groups.ResultsA total of 222 all-cause mortality (ACMs), 164 cardiac mortality (CMs), 718 major adverse cardiovascular events (MACEs) and 803 major adverse cardiovascular and cerebrovascular events (MACCEs) were recorded during follow-up period. A nonlinear relationship between FFA and adverse outcomes was observed only in CAD patients with hypertension. Namely, a “U -shape” relationship between FFA levels and long-term outcomes was found in CAD patients with hypertension. Lower FFA level (< 310 µmol/L), or higher FFA level (≥ 580 µmol/L) at baseline is independent risk factors for adverse outcomes. After adjustment for confounders, excess FFA increases mortality (ACM, HR = 1.957, 95%CI(1.240–3.087), P = 0.004; CM, HR = 2.704, 95%CI(1.495–4.890, P = 0.001) and MACE (HR = 1.411, 95%CI(1.077–1.848), P = 0.012), MACCE (HR = 1.299, 95%CI (1.013–1.666), P = 0.040) prevalence. Low levels of FFA at baseline can also increase the incidence of MACE (HR = 1.567,95%CI (1.187–2.069), P = 0.002) and MACCE (HR = 1.387, 95%CI (1.070–1.798), P = 0.013).ConclusionsBaseline FFA concentrations significantly associated with long-term mortality and ischemic events could be a better and novel risk biomarker for prognosis prediction in CAD patients with hypertension.Trial registrationThe details of the design were registered on https://www.chictr.org.cn/ (Identifier NCT05174143).

The abnormalities of free fatty acid metabolism in patients with hypertrophic cardiomyopathy, a single-center retrospective observational study

BackgroundPrevious studies have shown the importance of energy deficiency and malfunctioning mitochondria in the pathophysiology of hypertrophic cardiomyopathy (HCM). There has been a little research into the relationship between plasma free fatty acids (FFA), one of the heart’s main energy sources, and HCM. We evaluated its clinical importance in HCM to see if there was a link between plasma FFA metabolism and HCM.MethodsIn a single-center retrospective observational study, we investigated 420 HCM patients diagnosed at Beijing Anzhen Hospital between January 1, 2018, and December 31, 2022. Meanwhile, 1372 individuals without HCM (non-HCM) were recruited. 391 non-HCM patients were chosen as controls via a propensity score matching (PSM) study with a 1:1 ratio.ResultsFFA in HCM patients showed statistically significant correlations with creatinine (r = 0.115, p = 0.023), estimated GFR (r=-0.130, p = 0.010), BNP (r = 0.152, p = 0.007), LVEF (r=-0.227, p < 0.001), LVFS (r=-0.160, p = 0.002), and LAD (r = 0.112, p = 0.028). Higher FFA levels were found in HCM patients who had atrial fibrillation and NYHY functional classes III or IV (p = 0.015 and p = 0.022, respectively). In HCM patients, multiple linear regression analysis revealed that BNP and LVEF had independent relationships with increasing FFA (Standardized = 0.139, p = 0.013 and =-0.196, p < 0.001, respectively).ConclusionsAmong HCM patients, the plasma FFA concentration was lower, and those with AF and NYHY functional class III or IV had higher FFA levels, and LVEF and BNP were independently associated with increasing FFA. The findings of the study should help inspire future efforts to better understand how energy deficiency contributes to hypertrophic cardiomyopathy (HCM) development.

Adipose Tissue Protects against Hepatic Steatosis in Male Rats Fed a High-Fat Diet plus Liquid Fructose: Sex-Related Differences.

Non-alcoholic fatty liver disease is a sexual dimorphic disease, with adipose tissue playing an essential role. Our previous work showed that female rats fed a high-fat high-fructose diet devoid of cholesterol (HFHFr) developed simple hepatic steatosis dissociated from obesity. This study assessed the impact of the HFHFr diet on the male rat metabolism compared with data obtained for female rats. A total of 16 Sprague Dawley (SD) male rats were fed either a control (standard rodent chow and water) or HFHFr (high-fat diet devoid of cholesterol, plus 10% fructose in drinking water) diet for 3 months. Unlike female rats, and despite similar increases in energy consumption, HFHFr males showed increased adiposity and hyperleptinemia. The expression of hormone-sensitive lipase in the subcutaneous white adipose tissue was enhanced, leading to high free fatty acid and glycerol serum levels. HFHFr males presented hypertriglyceridemia, but not hepatic steatosis, partially due to enhanced liver PPARα-related fatty acid β-oxidation and the VLDL-promoting effect of leptin. In conclusion, the SD rats showed a sex-related dimorphic response to the HFHFr diet. Contrary to previous results for HFHFr female rats, the male rats were able to expand the adipose tissue, increase fatty acid catabolism, or export it as VLDL, avoiding liver lipid deposition.

Establishing mammalian GLUT kinetics and lipid composition influences in a reconstituted-liposome system

Glucose transporters (GLUTs) are essential for organism-wide glucose homeostasis in mammals, and their dysfunction is associated with numerous diseases, such as diabetes and cancer. Despite structural advances, transport assays using purified GLUTs have proven to be difficult to implement, hampering deeper mechanistic insights. Here, we have optimized a transport assay in liposomes for the fructose-specific isoform GLUT5. By combining lipidomic analysis with native MS and thermal-shift assays, we replicate the GLUT5 transport activities seen in crude lipids using a small number of synthetic lipids. We conclude that GLUT5 is only active under a specific range of membrane fluidity, and that human GLUT1-4 prefers a similar lipid composition to GLUT5. Although GLUT3 is designated as the high-affinity glucose transporter, in vitro D-glucose kinetics demonstrates that GLUT1 and GLUT3 actually have a similar KM, but GLUT3 has a higher turnover. Interestingly, GLUT4 has a high KM for D-glucose and yet a very slow turnover, which may have evolved to ensure uptake regulation by insulin-dependent trafficking. Overall, we outline a much-needed transport assay for measuring GLUT kinetics and our analysis implies that high-levels of free fatty acid in membranes, as found in those suffering from metabolic disorders, could directly impair glucose uptake.

1539-P: Effects of Free Fatty Acids (FFA) on Central Regulation of Glucose Metabolism

Activation of hypothalamic KATP channels reduces endogenous glucose production (EGP) in nondiabetic rodents and humans, but this response is lost in T2D. Lowering FFA with nicotinic acid (NA) restored central regulation of EGP in T2D subjects (Diabetes 2019; 1799P). High FFA levels, typical of T2D, may increase endoplasmic reticulum (ER) stress and thereby impair hypothalamic control of EGP. To explore how increased FFA might impact central regulation of EGP, we harvested hypothalamic wedges from n=10 Zucker Diabetic Fatty (ZDF) rats (glucose ~ 370 mg/dL) following infusion of NA or saline (Alzet minipump) for 18 h. Nondiabetic rats (n=5) were studied as controls. Gene expression of KATP channel subunit Kir6.2 was decreased in ZDF rats. Upon lowering FFA with NA, hypothalamic expression of this major subunit was restored (Fig 1a). Conversely, increased expression of genes regulating ER stress was reversed by NA (Fig 1b). Directly treating ZDF rat brain slices with NA did not alter the expression of these genes, suggesting that NA's effects were mediated by lowering FFA (Fig 1c). In conclusion, hypothalamic effects of elevated FFA include reduced KATPchannel expression and increased expression of ER stress genes, both of which may contribute reversibly to the loss of central regulation of EGP in T2D. These findings are consistent with our observations in humans noted above, suggesting that FFA could be a therapeutic target in T2D. Disclosure M. Nogueira Cordeiro: None. V.H. Routh: None. A. Manavalan: None. P.M. Mathias: None. C.E. Boyle: None. A.C. Rios Chen: None. N. Jiang: None. N. Friedman: None. Y. Demirhan: None. M. Hawkins: None. K. Zhang: None. Funding American Diabetes Association (7-08-CR-28 to M.H.); National Institutes of Health (R01DK069861); Diabetes Action Research and Education Foundation

Biodiesel Production from Waste Cooking Oil via β-Zeolite-Supported Sulfated Metal Oxide Catalyst Systems.

Waste cooking oil (WCO) is a readily available and cheap feedstock for biodiesel production. However, WCO contains high levels of free fatty acids (FFAs), which negatively impact the biodiesel yield if homogeneous catalysts are used. Heterogeneous solid acid catalysts are preferred for low-cost feedstocks because the catalysts are highly insensitive to high levels of FFA in the feedstock. Therefore, in the present study, we synthesized and evaluated different solid catalysts, pure β-zeolite, ZnO-β-zeolite, and SO42-/ZnO-β-zeolite for the production of biodiesel using WCO as feedstock. The synthesized catalysts were characterized by Fourier transform infrared spectroscopy (FTIR), pyridine-FTIR, N2 adsorption-desorption, X-ray diffraction, thermogravimetric analysis, and scanning electron microscopy, while the biodiesel product was analyzed using nuclear magnetic resonance (1H and 13C NMR) and gas chromatography-mass spectroscopy. The results revealed that the SO42-/ZnO-β-zeolite catalyst showed excellent catalytic performance for simultaneous transesterification and esterification of WCO, with a higher percentage conversion than the ZnO-β-zeolite and pure β-zeolite catalyst, due to the large pore size and high acidity. The SO42-/ZnO-β-zeolite catalyst exhibits 6.5 nm pore size, a total pore volume of 0.17 cm3/g, and high surface area of 250.26 m2/g. Experimental parameters such as catalyst loading, methanol:oil molar ratio, temperature, and reaction time were varied in order to establish the optimal parameters. The highest WCO conversion of 96.9% was obtained using the SO42-/ZnO-β-zeolite catalyst under an optimum reaction condition of 3.0 wt % catalyst loading, 200 °C reaction temperature, and 15:1 molar ratio of methanol to oil in 8 h reaction time. The WCO-derived biodiesel properties conform to the ASTM6751 standard specification. Our investigation of its kinetics revealed that the reaction follows a pseudo first-order kinetic model, with an activation energy (Ea) of 38.58 kJ/mol. Moreover, the stability and reusability of the catalysts were evaluated, and it was found that the SO42-/ZnO-β-zeolite catalyst exhibited good stability, giving a biodiesel conversion of over 80% after three synthesis cycles.

Denosumab Attenuates Glucolipotoxicity-Induced β-Cell Dysfunction and Apoptosis by Attenuating RANK/RANKL Signals.

Obesity is strongly associated with insulin sensitivity in type 2 diabetes (T2D), mainly because free fatty acids (FFAs) are released from excess fat tissue. Long-term exposure to high levels of FFAs and glucose leads to glucolipotoxicity, causing damage to pancreatic β-cells, thus accelerating the progression of T2D. Therefore, the prevention of β-cell dysfunction and apoptosis is essential to prevent the development of T2D. Unfortunately, there are currently no specific clinical strategies for protecting β-cells, highlighting the need for effective therapies or preventive approaches to improve the survival of β-cells in T2D. Interestingly, recent studies have shown that the monoclonal antibody denosumab (DMB), used in osteoporosis, displays a positive effect on blood glucose regulation in patients with T2D. DMB acts as an osteoprotegerin (OPG) by inhibiting the receptor activator of the NF-κB ligand (RANKL), preventing the maturation and function of osteoclasts. However, the exact mechanism by which the RANK/RANKL signal affects glucose homeostasis has not been fully explained. The present study used human 1.4 × 107 β-cells to simulate the T2D metabolic condition of high glucose and free fatty acids (FFAs), and it investigated the ability of DMB to protect β-cells from glucolipotoxicity. Our results show that DMB effectively attenuated the cell dysfunction and apoptosis caused by high glucose and FFAs in β-cells. This may be caused by blocking the RANK/RANKL pathway that reduced mammalian sterile 20-like kinase 1 (MST1) activation and indirectly increased pancreatic and duodenal homeobox 1 (PDX-1) expression. Furthermore, the increase in inflammatory cytokines and ROS caused by the RANK/RANKL signal also played an important role in glucolipotoxicity-induced cytotoxicity, and DMB can also protect β-cells by reducing the mechanisms mentioned above. These findings provide detailed molecular mechanisms for the future development of DMB as a potential protective agent of β-cells.

Effect of Pemafibrate on Hemorheology in Patients with Hypertriglyceridemia and Aggravated Blood Fluidity Associated with Type 2 Diabetes or Metabolic Syndrome

Persistent high serum triglyceride (TG) and free fatty acid (FFA) levels, which are common in metabolic syndrome and type 2 diabetes, are risk factors for cardiovascular events because of exacerbated hemorheology. To explore the effects of pemafibrate, a selective peroxisome proliferator-activated receptor alpha modulator, on hemorheology, we performed a single-center, nonrandomized, controlled study in patients with type 2 diabetes (HbA1c 6-10%) or metabolic syndrome, with fasting TG levels of ≥ 150 mg/dL and a whole blood transit time of > 45 s on a microarray channel flow analyzer (MCFAN). Patients were divided into a study group, receiving 0.2 mg/day of pemafibrate (n = 50) for 16 weeks, and a non-pemafibrate control group (n = 46). Blood samples were drawn 8 and 16 weeks after entry to the study to evaluate whole blood transit time as a hemorheological parameter, leukocyte activity by MCFAN, and serum FFA levels. No serious adverse events were observed in either of the groups. After 16 weeks, the pemafibrate group showed a 38.6% reduction in triglycerides and a 50.7% reduction in remnant lipoproteins. Pemafibrate treatment did not significantly improve whole blood rheology or leukocyte activity in patients with type 2 diabetes mellitus or metabolic syndrome complicated by hypertriglyceridemia and exacerbated hemorheology.

Influence of free fatty acid content and degree of fat saturation in laying hen diets on egg quality, yolk fatty acid profile, and cholesterol content

The aim of the present study was to evaluate the effect of dietary free fatty acid (FFA) content and the degree of saturation on egg quality, yolk fatty acid (FA) profile, and yolk cholesterol content. For a 15-wk period, a total of 144 laying hens (19-wk-old) were randomly assigned to 8 treatments arranged in a 2×4 factorial design, with 2 sources of crude oil (soybean oil and palm oil) and 4 levels of FFA (10, 20, 30, and 45%). The dietary treatments were achieved by progressively substituting the original oils with equivalent amounts of their corresponding acid oils (soybean acid oil and palm fatty acid distillate, respectively). No differences in ADFI or egg mass were found. However, dietary FFA reduced egg production (linear, P < 0.05) and increased the feed conversion ratio (linear, P < 0.05). Higher levels of FFA in soybean diets resulted in higher egg weight with higher albumen and yolk weights (linear, P < 0.01). Palm diets presented higher yolk:albumen ratio than soybean diets (P < 0.001), but the effect of FFA did not follow a linear trend. Hens fed soybean diets laid eggs with higher Haugh units (HU) than palm diets (P < 0.001), although increasing the dietary FFA% reduced the HU values in both (linear, P < 0.001). Palm diets enhanced shell quality with greater resistance to breakage, and higher dry matter and ash content than soybean diets (P < 0.05). No differences in egg chemical composition and yolk cholesterol content were found (P > 0.05). The saturation degree had a significant effect on all the analyzed yolk FA (P < 0.001) except for arachidonic acid (C20:4 n-6), whereas increasing the FFA content did not affect to a great extent. These results show that varying dietary FFA level did not affect egg quality and yolk composition as much as the dietary fat source did, supporting the use of acid oils and fatty acid distillates as fat ingredients for feed.

Plasma fingerprint of free fatty acids and their correlations with the traditional cardiac biomarkers in patients with type 2 diabetes complicated by coronary heart disease.

Type 2 diabetes mellitus (T2DM) is a well-established risk factor for cardiovascular disease, with at least 2–3 fold higher risk of cardiovascular diseases than non-diabetics. Free fatty acids (FFAs) are believed to play important roles in the occurrence of cardiovascular disease in people with T2DM. The aim of this study was to investigate the fingerprint of plasma FFAs and their correlations with the tradition risk factors of cardiovascular disease in T2DM patients complicated by coronary heart disease (CHD-T2DM). A total of 401 participants, including healthy control (HC, n = 143), T2DM patients (n = 134), and CHD-T2DM patients (n = 126) were enrolled in this study. Plasma levels of 36 FFAs with carbon chain length ranged from 3 to 22 were quantified by using reverse phase ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). Tradition risk factors of cardiovascular disease were tested in clinical laboratory, including homocysteine (HCY), creatine kinase (CK), high sensitivity C reactive protein (hsCRP), and N-terminal pro-brain natriuretic peptide (NT-proBNP) and so on. Almost all the FFAs with different carbon chain length and unsaturation were significantly upregulated in the T2DM-CHD groups, compared to the HC and T2DM groups. Both n-3 and n-6 polyunsaturated fatty acids (PUFA) were also found to be significantly upregulated in T2DM-CHD group compared to the T2DM group. However, no significantly differences of the n-6/n-3 PUFA ratio, arachidonic acid/eicosapentaenoic acid (AA/EPA) ratio, and arachidonic acid/docosahexaenoic acid (AA/DHA) ratio were observed between T2DM-CHD and T2DM groups. Plasma FFA levels were found to be positively correlated with HCY, CK, hsCRP, NT-proBNP and other tradition risk factors of CHD. Multivariate logistic regression analysis indicated that a dozens of FFAs were the independent risk factors of CHD after adjustment for confounding factors and other risk factors. Excessively high plasma levels of FFAs were demonstrated to be independent risk factors for CHD in patients with T2DM, despite of the differences in chain length, unsaturation, and double bond position.

Preoperative Oral Carbohydrate Levels in Patients with Type 2 Diabetes Mellitus: The Clinical Guiding Significance of Free Fatty Acids.

BackgroundIt is still controversial whether preoperative oral carbohydrate (POC) should be applied to patients with type 2 diabetes mellitus (T2DM) in the enhanced recovery after surgery (ERAS) protocol. There is no relevant consensus or indicators to provide guidance as to whether T2DM patients should take POC.MethodsIn total, 164 T2DM patients who underwent laparoscopic hepatectomy were analyzed. According to the level of blood free fatty acids (FFAs) and whether the patients received POC, the patients were divided into 6 groups: the low FFA carbohydrate group (LFFAC group), low FFA fasting water group (LFFAF group), medium FFA carbohydrate group (MFFAC group), medium FFA fasting water group (MFFAF group), high FFA carbohydrate group (HFFAC group) and high FFA fasting water group (HFFAF group).ResultsPatients with low FFA levels showed better perioperative blood glucose control and a lower incidence of postoperative complications than those in the medium and high FFA groups, especially when patients received POC. Further analyses revealed that the postoperative plasma concentrations of IL-6 and TNF-α were significantly decreased in the POC group compared with the fasting water group, except for patients with high FFA levels. Receiver operating characteristic (ROC) curve analysis revealed that when the FFA concentration was higher than 0.745 mmol/L, the risk of poor blood glucose control during the perioperative period was increased.ConclusionsFFAs have clinical guiding significance for the application of POC in patients with T2DM under ERAS administration. T2DM patients with low FFAs are more suitable for receiving POC.

Time Course of Fat Accumulation in Various Organs of Young OLETF Rats

PurposeExcessive fat accumulation induces chronic inflammation in the white adipose tissue (WAT), which leads and accelerates to obesity‐related health problems such as glucose intolerance, insulin resistance, and dyslipidemia. Determination of the time course of fat accumulation in obesity might allow identification of target tissues to treat the health problems in each stage. The purpose of the present study was to investigate the relationship between inflammatory changes and time course of fat accumulation in various organs.MethodsMale Otsuka Long‐Evans Tokushima fatty (OLETF) rats were used as spontaneous obesity animals. All rats were fed a standard diet containing 55.3% carbohydrate and water ad libitum. From 4‐ to 20‐week‐old, blood samples from vena cava and samples of the epididymal adipose tissue, retroperitoneal adipose tissue, mesenteric adipose tissue, and inguinal subcutaneous adipose tissue as WAT, brown adipose tissue (BAT) from interscapular region, liver, pancreas, and plantaris muscles were analyzed histologically every 2 weeks. Collected serum was used to detect triglyceride (TG) and free fatty acid (FFA) concentrations. Tissue samples were sliced and stained with hematoxylin and eosin or oil red O for histological observation.ResultsBody weight in OLETF rats increased linearly from 4‐ to 20‐week‐old. Although the wet weight and adipocyte diameter of the epididymal adipose tissue also increased throughout the experimental period, the values of inguinal subcutaneous adipose tissue increased by 10‐week‐old and were almost the same after 10‐week‐old. The liver TG levels increased from 4‐ to 8‐week‐old. However, hypertriglyceridemia, BAT whitening, and hepatic steatosis were not observed at this period. The serum TG levels increased after 10‐week‐old. Additionally, the number of whitened unilocular adipocytes with a diameter &gt;10 μm in the BAT increased after 10‐week‐old and oil red O positive lipid droplets were usually observed in the liver at this period. Not only the serum TG levels but also the serum FFA levels increased after 18‐week‐old. Additionally, enlarged adipocytes with a diameter &gt;130 μm and crown like structure indicating inflammatory change were often observed in the epididymal adipose tissue and retroperitoneal adipose tissue, not in mesenteric adipose tissue and inguinal subcutaneous adipose tissue, at this period. Fatty pancreas and intramuscular fat deposition were not observed throughout the experimental period.ConclusionAdipocyte hypertrophy in the visceral WAT and fatty liver could precede dyslipidemia in young OLETF rats and continuous obesity subsequently proceed to ectopic fat accumulation including BAT whitening and chronic inflammation in the epididymal adipose tissue and retroperitoneal adipose tissue with higher FFA levels. Hyperphagia mainly on carbohydrate could contribute to ectopic fat accumulation in the liver and BAT whitening, not to fatty pancreas and intramuscular fat deposition in young stage.

ANALYSIS OF CRUDE PALM OIL (CPO) QUALITY BASED ON VACUUM DRYER PERFORMANCE AT PRIMAJASA PALM OIL MILL

The products produced at the Primajasa Palm Oil Mill are Crude Palm Oil (CPO) and palm kernel (kernel). The palm oil processing process goes through several stations, including loading ramp station, sterilizing station, threshing stations, digesting and pressing station, clarification station, and kernel stations. In the palm oil processing industry, the main factors that can cause damage palm oil quality are high moisture content and free fatty acid (FFA) levels. This study aims to analyze the quality of CPO based on the performance of the vacuum dryer at the Primajasa Palm Oil Mill as seen from the free fatty acid (FFA) and moisture content. The average results obtained from the analysis of the moisture content of CPO before entering the vacuum dryer and after leaving the vacuum dryer were 0.57% and 0.27%. Meanwhile, the average results obtained from the analysis of FFA CPO levels before entering the vacuum dryer and after leaving the vacuum dryer were 3.63% and 3.57%. Based on these results, it is known that a vacuum dryer can reduce the value of moisture content and FFA levels contained in CPO. These results also indicate that the moisture content and free fatty acid (FFA) content in the sample are in accordance with the national quality standard of CPO.

AICAR Protects Vascular Endothelial Cells from Oxidative Injury Induced by the Long-Term Palmitate Excess.

Hyperlipidemia manifested by high blood levels of free fatty acids (FFA) and lipoprotein triglycerides is critical for the progression of type 2 diabetes (T2D) and its cardiovascular complications via vascular endothelial dysfunction. However, attempts to assess high FFA effects in endothelial culture often result in early cell apoptosis that poorly recapitulates a much slower pace of vascular deterioration in vivo and does not provide for the longer-term studies of endothelial lipotoxicity in vitro. Here, we report that palmitate (PA), a typical FFA, does not impair, by itself, endothelial barrier and insulin signaling in human umbilical vein endothelial cells (HUVEC), but increases NO release, reactive oxygen species (ROS) generation, and protein labeling by malondialdehyde (MDA) hallmarking oxidative stress and increased lipid peroxidation. This PA-induced stress eventually resulted in the loss of cell viability coincident with loss of insulin signaling. Supplementation with 5-aminoimidazole-4-carboxamide-riboside (AICAR) increased endothelial AMP-activated protein kinase (AMPK) activity, supported insulin signaling, and prevented the PA-induced increases in NO, ROS, and MDA, thus allowing to maintain HUVEC viability and barrier, and providing the means to study the long-term effects of high FFA levels in endothelial cultures. An upgraded cell-based model reproduces FFA-induced insulin resistance by demonstrating decreased NO production by vascular endothelium.

The effect of different intravenous lipids on free bilirubin levels in premature infants.

Intravenous lipid emulsions are commonly used as a part of parenteral nutrition in premature infants. The potential bilirubin-displacing effects of high free fatty acid (FFA) levels during lipid infusions are known. Levels of free bilirubin (FB) predict the risk of bilirubin neurotoxicity more accurately than indirect serum bilirubin levels. In the present study, we decided to compare the effect of two different lipid solutions on free bilirubin and free fatty acids levels in premature infants. Infants were grouped into two groups according to intravenous lipid preparations: Infants in Group 1 received lipid emulsion containing olive oil + soybean oil and Group 2 received containing olive oil + soybean oil + fish oil. The blood samples were gained when lipid intake was 3.5 g/kg/day and FFA and FB levels were analyzed. Serum FFA and FB levels were similar in groups (p = 0.26 and 0.69 respectively). There were significant correlation between serum FFA and FB levels in Group 1 (r = 0.74, p < 0.001) and in Group 2 (r = 0.92, p < 0.001). Both lipid preparations seem to have similar effects on free bilirubin and free fatty acid levels in premature newborns.

Association of obesity with serum free fatty acid levels in individuals at different stages of prediabetes

We investigated the associations of prediabetes categories and obesity with serum free fatty acid (FFA) levels and adipose tissue insulin resistance. This study included 5006 male participants (1779, 1025, 629, 874, and 699 with normal fasting glucose/normal glucose tolerance, isolated impaired fasting glucose [IFG], isolated impaired glucose tolerance [IGT], IFG plus IGT, and diabetes, respectively). Serum FFA levels were assessed before and 30, 60, and 120 min after glucose ingestion, and the total area under the FFA curve (AUCFFA ) was calculated. Adipose insulin resistance index (adipo-IR) was assessed based on fasting FFA and insulin concentrations. Isolated IFG was associated with high fasting FFA levels (OR, 1.35; p < 0.001) and high adipo-IR (OR, 1.82; p < 0.001) only in the nonobesity group. Isolated IGT, IFG plus IGT, and diabetes were associated with high fasting FFA levels, regardless of obesity. Obesity was significantly associated with AUCFFA , and the duration of obesity-related impairment in lipolysis inhibition after glucose ingestion was prolonged in IFG plus IGT and diabetes. These results suggest that IFG and obesity may overlap in their effects on FFA metabolism whereas IGT has significant effects on FFA independent of obesity. Obesity impact on lipolysis may be involved in worsening glucose metabolism.