Free Fatty Acid Levels Research Articles

ACADM inhibits AMPK activation to modulate PEDV-induced lipophagy and β-oxidation for impairing viral replication

Porcine epidemic diarrhea virus (PEDV) belongs to the Alphacoronavirus genus within the Coronavirus family, causing severe watery diarrhea in piglets and resulting in significant economic losses. Medium-chain acyl-CoA dehydrogenase (ACADM) is an enzyme participating in lipid metabolism associated with metabolic diseases and pathogen infections. Nonetheless, the precise role of ACADM in regulating PEDV replication remains uncertain. In this study, we identified ACADM as the host binding partner of NSP4 via immunoprecipitation-mass spectrometry analysis. The interaction between ACADM and NSP4 was subsequently corroborated through coimmunoprecipitation and laser confocal microscopy. Following this, a notable upsurge in ACADM expression was observed during PEDV infection. ACADM overexpression effectively inhibited virus replication, whereas ACADM knockdown facilitated virus replication, suggesting ACADM has negative regulation effect on PEDV infection. Furthermore, we demonstrated fatty acid β-oxidation affected PEDV replication for the first time, inhibition of fatty acid β-oxidation reduced PEDV replication. ACADM decreased PEDV-induced β-oxidation to suppress PEDV replication. Mechanistically, ACADM reduced cellular free fatty acid levels and subsequent β-oxidation by hindering AMPK-mediated lipophagy. In summary, our results reveal that ACADM plays a negative regulatory role in PEDV replication by regulating lipid metabolism. The present study introduces a novel approach for the prevention and control of PEDV infection.

Gut Microbiota Regulate Saturated Free Fatty Acid Metabolism in Heart Failure

Aims: Heart failure (HF) is associated with profound changes in cardiac metabolism. At present, there is still a lack of relevant research to explore the key microbiome and their metabolites affecting the progression of HF. Herein, the interaction of gut microbiota and circulating free fatty acid (FFA) in HF patients and mice is investigated. Methods and Results: In HF patients, by applying metagenomics analysis and targeted FFA metabolomics, enriched abundance of Clostridium sporogenes (C.sp) in early and late stage of HF patients, which negatively correlated to saturated free fatty acid (SFA) levels, is identified. KEGG analysis further indicates microbiota gene enrichment in FFA degradation in early HF, and decreased gene expression in FFA synthesis in late HF. In HF mice (C57BL/6J) induced by isoproterenol (ISO), impaired intestinal permeability is observed, and decreased fecal C.sp and increased SFA are further validated. At last, by supplementing C.sp to ISO‐induced HF mice, the cardiac function, fibrosis, and myocardial size are partially rescued, together with decreased circulating SFA levels. Conclusions: Clostridium abundance is increased in HF, compensating cardiac function deterioration via downregulation of circulating SFA levels. The results demonstrate that the gut microbiota–SFA axis plays an important role in HF protection, which may provide a strategic advantage for the probiotic therapy development in HF.

Shelf-Life Prediction of Shredded Duck “Cahyo” by Accelerated Shelf-Life Testing (ASLT) technique Based on The Arrhenius Model

Shredded Duck "Cahyo" PT Deltasari Indah Restaurant is a shredded product made from duck meat. The shelf life of Shredded Duck "Cahyo" can be used as an indication in determining the time and expiration date. Expiration information is one of the important information that must be included in each food packaging. examinations made from the repository to changes in quality decline are carried out to decide the shelf life of Shredded Duck "Cahyo". Therefore, a study was conducted to forecast the shelf life of Shredded Duck "Cahyo" PT Deltasari Indah Restaurant. This study's objectives are to decide the critical criteria for determining the shelf life of Shredded Duck "Cahyo" and to forecast the shelf life of Shredded Duck "Cahyo" products stored at different thermal state conditions. In this study, Accelerated Shelf Life Testing utilizing the Arrhenius model was employed. Shredded Duck "Cahyo" packaged in PET jars underwent repository at thermal states of 30˚C, 40˚C, and 50˚C for 28 days, by examinations conducted every 7 days. Key criteria analyzed encompassed water content, Free Fatty Acid (FFA) levels, and total microbial presence. The critical criterion selected was the Free Fatty Acid (FFA) criterion, given its low activation energy (Ea) and high R2 value. outcomes indicated that utilizing the Arrhenius model ASLT approach, the shelf lives of Shredded Duck "Cahyo" at 30˚C, 40˚C, and 50˚C were 58 days, 51 days, and 44 days, respectively. Considering actual repository conditions (20˚C and 25˚C), the average shelf life of Shredded Duck "Cahyo" was decided to be 65.5 days.

The association between serum free fatty acid levels and neurological outcomes in out-of-hospital cardiac arrest patients: A prospective observational study.

Free fatty acids (FFA) are a known risk factor in the development of sudden cardiac death. However, the relationship between FFA and the outcome of out-of-hospital cardiac arrest (OHCA) patients remains unclear. We aimed to examine the association between FFA and neurological outcomes in OHCA patients. This prospective observational study included adult (≥18 years) OHCA patients between February 2016 and December 2022. We measured serial FFA levels within 1 hour after ROSC and at 6, 12, 24, 48, and 72 hours after the return of spontaneous circulation (ROSC). The primary outcome was neurological outcome at 6 months. A poor neurological outcome was defined by cerebral performance categories 3, 4, and 5. A total of 147 patients were included. Of them, 104 (70.7%) had poor neurological outcomes, whereby the median FFA levels within 1 hour after ROSC (0.72 vs 1.01 mol/L), at 6 hours (1.19 vs 1.90 mol/L), 12 hours (1.20 vs 1.66 mol/L), and 24 hours (1.20 vs 1.95 mol/L) after ROSC were significantly lower than in good outcome group. The FFA levels at 6 hours (odds ratio, 0.583; 95% confidence interval, 0.370-0.919; P = .020), and 12 hours (odds ratio, 0.509; 95% confidence interval, 0.303-0.854; P = .011) after ROSC were independently associated with poor neurological outcomes. The lower FFA levels at 6 hours and 12 hours after ROSC were associated with poor neurological outcomes in patients with OHCA. FFA may reflect oxidative metabolism as well as oxidative stress.

An Increasing Triglyceride-Glucose Index Is Associated with a Pro-Inflammatory and Pro-Oxidant Phenotype.

Background/Objectives: Insulin resistance is crucial in the pathogenesis of Metabolic Syndrome (MetS), type 2 diabetes mellitus (T2DM) and premature atherosclerotic cardiovascular disease (ASCVD). The triglyceride-glucose index (TyG index), a validated measure of insulin resistance, also predicts MetS, T2DM, the severity of albuminuria and ASCVD. There are scant data providing mechanistic insights into these sequalae. Accordingly, we investigated the relationship between the TyG index and biomarkers of inflammation, oxidative stress, free fatty acid (FFA) levels and adipokine dysregulation in a cohort comprising both controls and patients with nascent MetS. Methods: Participants (n = 102) included 59 patients with MetS and 43 controls. People with diabetes, ASCVD, smoking and macro-inflammation were excluded. Fasting blood was obtained for both plasma and monocyte isolation. Results: Receiver Operating Characteristic (ROC) curve analysis revealed that the TyG index was an excellent predictor of MetS with an area under the curve of 0.87, and it correlated with both hepatic and adipose tissue insulin resistance. Both serum RBP-4 levels and non-HDL cholesterol increased significantly over tertiles of the TyG index. Based on the TyG index tertiles and/or correlations, oxidized LDL, nitrotyrosine, C-reactive protein, endotoxin, chemerin, interleukin-6 levels and monocyte toll-like receptor (TLR)-4 and TLR-2 and their cellular signaling were significantly associated with the TyG index. Conclusions: Increased non-HDL-C and, most importantly, a pro-inflammatory and pro-oxidant state could be advanced as potential mechanisms explaining the increased risk for T2DM and ASCVD with an increasing TyG index.

Impact of Lipids on Insulin Resistance: Insights from Human and Animal Studies.

Insulin resistance (IR) is a complex pathological condition central to metabolic diseases such as type 2 diabetes mellitus (T2DM), cardiovascular disease, non-alcoholic fatty liver disease, and polycystic ovary syndrome (PCOS). This review evaluates the impact of lipids on insulin resistance (IR) by analyzing findings from human and animal studies. The articles were searched on the PubMed database using two keywords: (1) "Role of Lipids AND Insulin Resistance AND Humans" and (2) "Role of Lipids AND Insulin Resistance AND Animal Models". Studies in humans revealed that elevated levels of free fatty acids (FFAs) and triglycerides (TGs) are closely associated with reduced insulin sensitivity, and interventions like metformin and omega-3 fatty acids show potential benefits. In animal models, high-fat diets disrupt insulin signaling and increase inflammation, with lipid mediators such as diacylglycerol (DAG) and ceramides playing significant roles. DAG activates protein kinase C, which eventually impairs insulin signaling, while ceramides inhibit Akt/PKB, further contributing to IR. Understanding these mechanisms is crucial for developing effective prevention and treatment strategies for IR-related diseases.

Effect of physical activity on free fatty acids, insulin resistance, and blood pressure in obese older women.

Obesity is characterized by a progressive increase in body fat accompanied by insulin resistance (IR) and elevated blood pressure (BP), and presents significant health risks, particularly in aged individuals. This study aimed to evaluate the effects of physical activity (PA) on free fatty acid (FFA) levels, IR, and BP in obese older women. Twenty-three participants were randomly assigned to either the control group (CON, n = 11) or the physical activity group (PA, n = 12). The PA group was provided with a target of achieving >7,000 steps/day for 5 days each week. Body composition, FFA levels, IR, and BP were measured at pre- and post- of the 12-week intervention. The analysis revealed a statistically significant interaction between FFA (p < 0.01), IR (p < 0.01), and SBP (p < 0.001). FFA (p < 0.5), IR (p < 0.5), and systolic blood pressure (SBP) (p < 0.01) were significantly decreased in the PA group compared to those in the CON group, which showed no significant changes in FFA, IR, and SBP. PA significantly decreased FFA, IR, and SBP in older women with obesity. Therefore, PA is an effective intervention for the prevention and management of obesity and cardiovascular diseases in obese older women.

ИССЛЕДОВАНИЕ ХИМИЧЕСКОГО СОСТАВА ЛИСТЬЕВ И ПЛОДОВ МОМОРДИКИ ХАРАНЦИЯ, ПРОИЗРАСТАЮЩЕЙ В КРАСНОДАРСКОМ КРАЕ

Momordica charantia L. is an annual climbing herbaceous plant of the pumpkin family (Cucurbitaceae), which is quite successfully cultivated in various areas with a temperate climate, including in the Krasnodar Territory. Along with the fact that the plant belongs to the food category, in folk medicine the fruits and leaves of Momordica charantia are used for diabetes, skin diseases, rheumatism, gout, and also as an anthelmintic and laxative. Data on the hypoglycemic effect of Momordica charantia fruit extract have been published, indicating its positive effect on insulin production, glucose metabolism, free fatty acid levels and kidney health in animal experiments and in clinical practice in patients with diabetes mellitus. The therapeutic activity of this plant is due to the rich composition of biologically active substances (BAS), which is characterized by the content of triterpene glycosides of the cucurbitan type, phenolic compounds, organic acids, fatty oil, proteins, lectins, pectin, inulin, alkaloids, macro- and microelements. As is known, the qualitative composition and quantitative content of biologically active substances in plant objects can vary significantly depending on the place of its growth and growing conditions. In this regard, it seemed appropriate to study the representation of a number of groups of chemical compounds in the fruits and leaves of Momordica charantia growing in the Krasnodar region. Among the biologically active substances that are essential for the prevention and treatment of various diseases are organic acids and minerals. Organic acids have anti-inflammatory, antiseptic, choleretic, and keratolytic effects. Minerals play an active role in the metabolism of proteins, lipids and carbohydrates, act as cofactors in chemical reactions, are part of cellular and skeletal structures, and participate in ensuring osmotic pressure and acid-base balance. The purpose of the study was to study the organic acids and minerals of the leaves and fruits of Momordica charantia, growing in the Krasnodar region. When carrying out the research, we used the leaves and fruits of Momordica charantia, harvested in the Krasnodar region and dried in the air-shadow method. The study was carried out by capillary electrophoresis using a Kapel-105M device (JSC NPF Lumex, Russia) with a quartz capillary Leff/Ltotal=50/60 cm, ID=75 µm. As a result of the research, the qualitative and quantitative composition of organic acids and minerals of the leaves and fruits of Momordica charantia, growing in the Krasnodar region, was studied. The presence of substances of these groups in combination with other biologically active substances is of scientific and practical interest from the point of view of the prospects for creating functional products for various purposes based on regional resources of the momordica.

Hydrogen-Rich Water (HRW) Reduces Fatty Acid-Induced Lipid Accumulation and Oxidative Stress Damage through Activating AMP-Activated Protein Kinase in HepG2 Cells.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by excessive fat accumulation in the liver. Intracellular oxidative stress induced by lipid accumulation leads to various hepatocellular injuries including fibrosis. However, no effective method for mitigating MASLD without substantial side effects currently exists. Molecular hydrogen (H2) has garnered attention due to its efficiency in neutralizing harmful reactive oxygen species (ROS) and its ability to penetrate cell membranes. Some clinical evidence suggests that H2 may alleviate fatty liver disease, but the precise molecular mechanisms, particularly the regulation of lipid droplet (LD) metabolism, remain unclear. This study utilized an in vitro model of hepatocyte lipid accumulation induced by free fatty acids (FFAs) to replicate MASLD in HepG2 cells. The results demonstrated a significant increase in LD accumulation due to elevated FFA levels. However, the addition of hydrogen-rich water (HRW) effectively reduced LD accumulation. HRW decreased the diameter of LDs and reduced lipid peroxidation and FFA-induced oxidative stress by activating the AMPK/Nrf2/HO-1 pathway. Overall, our findings suggest that HRW has potential as an adjunctive supplement in managing fatty liver disease by reducing LD accumulation and enhancing antioxidant pathways, presenting a novel strategy for impeding MASLD progression.

Effects of Konjac Glucomannan and Its Oligosaccharides on Improvement of Lactose Intolerance as Gut Prebiotics.

Lactose intolerance (LI) is a widespread health issue affecting almost 70% of the world population. This study evaluates the potential prebiotic benefits of konjac glucomannan (KGM) and konjac oligogalactomannan (KOGM) in improving LI. Colonic fermentation results indicate that lactase groups of healthy subjects showed lower pH, higher lactic acid content, and lactase activity in fermentation broth compared with LI subjects. Total short-chain fatty acid (SCFAs) content reached 1.71 mmol/L in healthy subjects, whereas it was 1.49 mmol/L in LI subjects. In vivo studies demonstrated that KGM and KOGM intake reduced total cholesterol (T-CHO) and triglyceride (TG) levels in the liver and significantly increased immunoglobulin G (lgG) and immunoglobulin A (lgA) values, while KOGM inclusion led to a significant 23.04% increase in serum free fatty acid (FFA) levels compared to the Blank group (p < 0.05). Furthermore, ileal tissue analysis revealed a marked increase in villus height and intestinal wall thickness (p < 0.05) as well as a decrease in crypt depth (p < 0.05). The composition and proportion of gut microbiota have improved with KGM and KOGM use, notably increasing the abundance of Lactobacillus and Lachnospiraceae_NK4A136_group, respectively (p < 0.05). Compared with the Blank group, Lactobacillus abundance increased by approximately 25.82% in the Drug group, 18.23% in the KGM group, and 8.67% in the KOGM group. These findings suggest that KGM and KOGM can be utilized as prebiotics to alleviate LI symptoms.

Effect of Microencapsulated Goat Clarified Butter on Free Fatty Acids and Physicochemical Properties in Cow Butter Production

In the study, goat clarified butter was encapsulated using a concentric nozzle and the microencapsulation process. The cow creams were mixed with encapsulated goat clarified butter in various quantities and left for a week. The study looked at the physical and chemical qualities, as well as the levels of free fatty acids and α-tocopherol, of cow butters that had different amounts of goat ghee microcapsules added to them. % Lactic acid, acid value, Polenske number, and α-tocopherol of cow butter all went up significantly when encapsulated goat butter was added (p

Transcriptome analysis reveals hepatic disordered lipid metabolism, lipotoxic injury, and abnormal development in IUGR sheep fetuses due to maternal undernutrition during late pregnancy

Although lipid metabolism in fetal livers under intrauterine growth restriction (IUGR) conditions has been widely studied, the implications of maternal undernutrition on fetal hepatic lipid metabolism, lipotoxic injury, and abnormal development remain largely unknown. Therefore, this study investigated the effects of maternal undernutrition on disordered hepatic lipid metabolism, lipotoxic injury, and abnormal development in IUGR sheep fetuses using transcriptome analysis. Seventeen singleton ewes were randomly divided into three groups on day 90 of pregnancy: a control group (CG; 0.63 MJ metabolic energy/body weight (ME/BW)0.75/day, n = 5), maternal undernutrition group 1 (MU1; 0.33 MJ ME/BW0.75/day, n = 6), and maternal undernutrition group 2 (MU2; 0.20 MJ ME/BW0.75/day, n = 6). The fetuses were euthanized and recovered on day 130 of pregnancy. The levels of free fatty acids (FFA) in maternal blood (P < 0.01), fetal blood (P < 0.01), and fetal livers (P < 0.05) were increased in the MU1 and MU2 groups, but fetal hepatic triglyceride (TG) levels in the MU2 group (P < 0.01) and β-hydroxybutyrate levels in the MU1 and MU2 groups (P < 0.01) were decreased compared to the CG. Severe inflammatory cell infiltration and increased non-alcoholic fatty liver disease activity scores were observed in MU1 and MU2 fetuses (P < 0.01). Progressive deposition of fetal hepatic reticular fibers and collagen fibers in the fetal livers of the MU1 and MU2 groups and significant hepatic fibrosis were observed in the MU2 fetuses (P < 0.05). Gene set enrichment analysis showed that genes involved in lipid accumulation and FFA beta oxidation were downregulated in both MU groups compared to those in the controls. The fetal liver mRNA expression of the β-oxidation regulator, acetyl-CoA acetyltransferase 1, and the TCA regulator, isocitrate dehydrogenase were reduced in MU1 (P < 0.05) and MU2 (P < 0.01) fetuses, and downregulated mRNA expression of long chain fatty acid CoA ligase 1 (P < 0.05) and glycerol-3-phosphate acyltransferase (P < 0.01) was observed in MU2 fetuses. Differentially expressed genes (DEGs) in MU1 versus CG (360 DEGs) and MU2 versus CG (746 DEGs) were identified using RNA sequencing. Bioinformatics analyses of the 231 intersecting DEGs between MU1 versus CG and MU2 versus CG indicated that neutrophil extracellular traps (NETs) were induced and played a central role in fetal hepatic injury in IUGR sheep. Increased maternal blood myeloperoxidase (MPO) levels (P < 0.01), NE (Elane)-positive areas in fetal liver sections (P < 0.05), and fetal liver MPO protein expression (P < 0.01) were found in the MU1 and MU2 groups; however, MPO levels were reduced in the fetal membrane (P < 0.01) and fetal blood (P < 0.05) in the MU1 group, and in the maternal-fetal placenta and fetal blood in the MU2 group (P < 0.01). Analysis of gene expression trends in the intersecting DEGs between MU1 versus CG (129 DEGs) and MU2 versus CG (515 DEGs) further revealed that 30 hub genes were essential regulators of the G2/M cell cycle, all of which were associated with hepatocellular carcinoma. G0/G1 phase cells of the fetal liver were reduced in the MU1 (P < 0.05) and MU2 (P < 0.01) groups, whereas G2/M phase cells were elevated in the MU1 and MU2 groups (P < 0.01). The representatives of upregulated hub genes and fetal liver protein expression of maternal embryonic leucine zipper kinase and protein regulator of cytokinesis 1 were progressively enhanced in the MU1 and MU2 groups (P < 0.01), and topoisomerase II alpha protein expression in the MU2 group (P < 0.05), as expected. These results indicate that FFA overload, severe lipotoxic injury, and NETs were induced, and disease-promoting regulators of the G2/M cell cycle were upregulated in the fetal liver of IUGR sheep. These findings provide new insights into the pathogenesis of impaired hepatic lipid metabolism and abnormal development and the molecular origin of post-natal liver disease in IUGR due to maternal undernutrition. This information can support the development of new therapeutic strategies.

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.

Effects of Intermittent Fasting and Sex on Blood Glucose, Free Fatty Acids, and Lipid Profile in Wistar Rats

Intermittent fasting (IF) has been reported to improve metabolic health through its effect on glucose and lipid profile. However, there is limited information on the effects of Intermittent Fasting on free fatty acids and sex related differences. This study was designed to investigate the effects of Intermittent Fasting (IF) on blood glucose, free fatty acids, lipid profile in both male and female Wistar rats and sex related differences. Twenty Wistar rats of both sexes weighing between 170-200g were used in the study. The animals were grouped into four (4) groups (n=5) per group. Groups 1 and 11 were male and female control groups respectively fed &amp;lt;i&amp;gt;ad libitum&amp;lt;/i&amp;gt; with feed and water while groups 111 and 1V were male and female intermittent fasting groups fasted for 16 hours and fed for 8 hours for 28 days respectively. They had free access to water for 24 hours. At the end of 28 days fasting, blood glucose, free fatty acids and lipid profile were determined. The results of the study showed that intermittent fasting was associated with a significant increase in free fatty acids in female rats (p&amp;lt; 0.05) but a non- significant increase in male rats. In both female and male rats, intermittent fasting was associated with a significant decrease (p&amp;lt; 0.05) ins blood glucose, total cholesterol, and low-density lipoprotein, but a non-significant decrease in triglyceride compared with control groups in both male and female rats. In conclusion, Intermittent fasting may help to improve blood glucose and maintain a balanced lipid profile in both males and females. However, Intermittent fasting may also raise the level of free fatty acids and the effect might be more pronounced in females.

Associations of body mass index with the level of free fatty acids in men

BACKGROUND: The people with an excessive amount of adipose tissue have elevated levels of free fatty acids (FFA) in the blood, which ultimately leads to disorders of lipid metabolism and insulin resistance, which are the main factors in the development of diabetes mellitus.AIM: To study the content of FFA in blood plasma, as well as their association with body weight in men.MATERIALS AND METHODS: A single-center observational one-stage study was conducted. The sample was formed by a random representative method, comparable by sex and age. The levels of FFA were determined in the blood plasma by high-performance liquid chromatography with mass spectrometry.RESULTS: The study included 250 men. The selected participants were divided into groups according to their body mass index (BMI): Group 1 — 62 people with BMI≤24.9 kg/m2, Group 2 — 101 people with BMI 25.0–29.9 kg/m2, Group 3 — 87 people with BMI≥30.0 kg/m2. Obese men were divided into: Group 4 — 62 people with BMI 30.0–34.9 kg/m2, Group 5 — 19 people with BMI 35.0–39.9 kg/m2, Group 6 — 6 people with BMI≥40.0 kg/m2.The content of docosatetraenoic acid was higher in groups 2 (p=0.002) and 5 (p=0.003), when compared with group 1. The content of gamma-linolenic acid was higher in group 3 than in group 1 (p=0.041). Concentration of oleic; linoleic; dihomo-gamma-linolenic; midic; arachidonic; eicosapentaenoic acids were higher in group 5 than in group 1 (p=0.007, p=0.023, p=0.004, p=0.019, p=0.006, p=0.001, respectively), and also than in group 2 (p=0.006, p=0.017, p=0.007, p=0.007, p=0.008, p=0.001, respectively). The content of nervonic acid is higher in groups 1 (p=0.029) and 2 (p=0.012) than in group 4. Obesity is associated with increased levels of gamma-linolenic (1.030, 1.006–1.056, p=0.015) and eicosapentaenoic acids (1.061, 1.000–1.125, p=0.045), and a decrease in the level of nervonic acid (0.953, 0.913–0.994, p=0.027).CONCLUSION: The FFA levels of blood plasma is significantly different in men with normal body weight and the presence of obesity. The content of oleic, gamma-linolenic, midic, digomo-gamma-linolenic, arachidonic, docosatetraenoic and ­eicosapentaenoic acids was significantly higher in men with grade 2 obesity. An increase in the level of gamma-linolenic and eicosapentaenoic acids, and a decrease in the level of nervonic acid are associated with obesity, regardless of the age.

The relationship of free fatty acid levels with cognitive status and neuroimaging characteristics in adolescents with obesity

The relationship of free fatty acid levels with cognitive status and neuroimaging characteristics in adolescents with obesity

Metabolic Responses to High-Fat Feeding and Chronic Psychological Stress Combination.

High-fat diet (HFD) consumption and being exposed to daily psychological stress, common environmental factors in modern lifestyle, play an important role on metabolic disorders such as glucose homeostasis impairment. The aim of this study was to investigate the effects of high-fat diet (HFD) and psychological stress combination on metabolic response to chronic psychological stress in male rats. Male Wistar rats were divided into HFD, and normal diet (ND) groups and then into stress and nonstress subgroups. The diets were applied for 5 weeks, and psychological stress was induced for 7 consecutive days. Then, blood samples were taken to measure glucose, insulin, free fatty acids (FFA), and leptin and corticosterone concentrations. Subsequently, glucose-stimulated insulin release from pancreatic isolated islets was assessed. HFD did not significantly change fasting plasma glucose, insulin and corticosterone levels, whereas increased plasma leptin (7.05 ± 0.33) and FFA (p < 0.01) levels and impaired glucose tolerance. Additionally, HFD and stress combination induced more profound glucose intolerance associated with increased plasma corticosterone (p < 0.01) and leptin (8.63 ± 0.38) levels. However, insulin secretion from isolated islets did not change in the presence of high-fat diet and/or stress. HFD should be considered as an intensified factor of metabolic impairments caused by chronic psychological stress.

Adipocyte pyroptosis occurs in omental tumor microenvironment and is associated with chemoresistance of ovarian cancer

BackgroundOvarian carcinoma (OC) is a fatal malignancy, with most patients experiencing recurrence and resistance to chemotherapy. In contrast to hematogenous metastasizing tumors, ovarian cancer cells disseminate within the peritoneal cavity, especially the omentum. Previously, we reported omental crown-like structure (CLS) number is associated with poor prognosis of advanced-stage OC. CLS that have pathologic features of a dead or dying adipocyte was surrounded by several macrophages is well known a histologic hallmark for inflammatory adipose tissue. In this study, we attempted to clarify the interaction between metastatic ovarian cancer cells and omental CLS, and to formulate a therapeutic strategy for advanced-stage ovarian cancer.MethodsA three-cell (including OC cells, adipocytes and macrophages) coculture model was established to mimic the omental tumor microenvironment (TME) of ovarian cancer. Caspase-1 activity, ATP and free fatty acids (FFA) levels were detected by commercial kits. An adipocyte organoid model was established to assess macrophages migration and infiltration. In vitro and in vivo experiments were performed for functional assays and therapeutic effect evaluations. Clinical OC tissue samples were collected for immunochemistry stain and statistics analysis.ResultsIn three-cell coculture model, OC cells-derived IL-6 and IL-8 could induce the occurrence of pyroptosis in omental adipocytes. The pyroptotic adipocytes release ATP to increase macrophage infiltration, release FFA into TME, uptake by OC cells to increase chemoresistance. From OC tumor samples study, we demonstrated patients with high gasdermin D (GSDMD) expression in omental adipocytes is highly correlated with chemoresistance and poor outcome in advanced-stage OC. In animal model, by pyroptosis inhibitor, DSF, effectively retarded tumor growth and prolonged mice survival.ConclusionsOmental adipocyte pyroptosis may contribute the chemoresistance in advanced stage OC. Omental adipocytes could release FFA and ATP through the GSDMD-mediate pyroptosis to induce chemoresistance and macrophages infiltration resulting the poor prognosis in advanced-stage OC. Inhibition of adipocyte pyroptosis may be a potential therapeutic modality in advanced-stage OC with omentum metastasis.

Elevated Lipid Metabolites in Stored Clinical OCA Media Correlate With Chondrocyte Death

Background: A major limitation of osteochondral allografts (OCA) is the deterioration of cartilage health associated with cell death during prolonged storage. However, little is known about the mechanisms that contribute to chondrocyte death during storage. Purpose/Hypothesis: This study aimed to determine whether bioactive lipid metabolites accumulate in the storage media of OCA and whether they are associated with a loss of chondrocyte viability during prolonged storage. It was hypothesized that free fatty acids (FFAs) would accumulate over time in the storage media of OCA and adversely affect cartilage health during storage. Study Design: Controlled laboratory study. Methods: A group of 21 (n = 6-8 OCA/treatment group) fresh human hemicondylar OCA tissues and media were analyzed after 7, 28, and 68 days of prolonged cold (4°C) storage. Targeted mass spectrometry analysis was used to quantify bioactive FFAs, as well as primary (lipid hydroperoxide [ROOH]) and secondary (malondialdehyde) lipid oxidation products. Chondrocyte viability was measured using a fluorescence-based live/dead assay and confocal microscopy. Results: The concentration of all targeted fatty acid metabolites in storage media was significantly increased with increased cold storage time (P < .05). ROOH was significantly higher on day 28 of cold storage. No difference in secondary ROOH products in storage media was observed. Chondrocyte viability significantly declined in both the en face and the vertical cross-sectional analysis with increased cold storage time and inversely correlated with fatty acid metabolites (P < .05). Conclusion: It is well established that elevated levels of certain FFAs and lipid oxidation products can alter cell function and cause cell death via lipotoxicity and other mechanisms. This work is the first to identify elevated levels of FFA metabolites and primary oxidation lipid products in the storage media from clinical OCA. The concentrations of FFA metabolites were measured at levels (>100 µM) known to induce cell death and were directly correlated with chondrocyte viability. Clinical Relevance: These findings provide important targets for understanding why cartilage health declines during cold storage, which can be used to optimize media formulations and improve graft health.

Risk factor analysis and establishment of a nomogram model to predict blood loss during total knee arthroplasty

PurposeThe risk factors for excessive blood loss and transfusion during total knee arthroplasty (TKA) remain unclear. The present study aimed to determine the risk factors for excessive blood loss and establish a predictive model for postoperative blood transfusion.MethodsThis retrospective study included 329 patients received TKA, who were randomly assigned to a training set (n = 229) or a test set (n = 100). Univariate and multivariate linear regression analyses were used to determine risk factors for excessive blood loss. Univariate and multivariate logistic regression analyses were used to determine risk factors for blood transfusion. R software was used to establish the prediction model. The accuracy and stability of the models were evaluated using calibration curves, consistency indices, and receiver operating characteristic (ROC) curve analysis.ResultsRisk factors for excessive blood loss included timing of using a tourniquet, the use of drainage, preoperative ESR, fibrinogen, HCT, ALB, and free fatty acid levels. Predictors in the nomogram included timing of using a tourniquet, the use of drainage, the use of TXA, preoperative ESR, HCT, and albumin levels. The area under the ROC curve was 0.855 (95% CI, 0.800 to 0.910) for the training set and 0.824 (95% CI, 0.740 to 0.909) for the test set. The consistency index values for the training and test sets were 0.855 and 0.824, respectively.ConclusionsRisk factors for excessive blood loss during and after TKA were determined, and a satisfactory and reliable nomogram model was designed to predict the risk for postoperative blood transfusion.