Serum Fatty Acid Research Articles

Pentachlorophenol increases diabetes risk by damaging β-cell secretion and disrupting gut microbial-related amino acids and fatty acids biosynthesis

Pentachlorophenol (PCP), a ubiquitous environmental pollutant, has been reported as a possible contributor to diabetes. However, evidence for general population is scarce while related mechanisms are largely unknown. Using a representative population-based case-control study in Beijing (n=1796), we found a positive association between PCP exposure and diabetes risk with the odds ratio reaching 1.68 (95% confidence interval: 1.30 to 2.18). A further rat experiment revealed that low-dose PCP mimicking real-world human exposure can significantly impair glycemic homeostasis by inducing pancreatic β-cell dysfunction, with non-linear dose-response relationships. Subsequent multi-omics analysis suggested that low-dose PCP led to notable gut microbiota dysbiosis (especially the species from genus Prevotella, such as intermedia, dentalis, ruminicola, denticola, melaninogenica, and oris), decreased serum amino acids (L-phenylalanine, L-tyrosine, and L-tryptophan) and increased serum fatty acids (oleic and palmitic acid) in rats, while strong correlations were observed among alterations of gut microbes, serum metabolites and glycemic-related biomarkers (e.g., fasting blood glucose and insulin). Collectively, these results imply PCP may increase diabetes risk by disrupting gut microbial-related amino acids and fatty acids biosynthesis. This will help guide future in-depth studies on the roles of PCP in the development of human diabetes.

Association between Serum Fatty Acids Profile and MetScore in Women with Severe Obesity

Background: Metabolic syndrome (MetS) is a set of conditions associated with an increased cardiovascular risk. Several serum fatty acids (FAs) seem to play an essential role in the development of cardiometabolic diseases and mortality. Thus, it is imperative to explore the impact of FAs on MetS parameters, using an early MetS screening tool such as MetScore, which is readily available in clinical practice. Aim: The aim of this study was to assess the potential correlation between serum FAs and cardiovascular risk using a MetScore. Methods: This cross-sectional study involved 41 women with severe obesity. The MetScore was calculated, and participants were categorized into high- and low-cardiovascular-risk groups based on the median MetScore value. Gas chromatography was used to quantify serum FAs. Generalized Linear Models were used to compare group means. The association was assessed through simple logistic regression, and an adjusted logistic regression was conducted to validate the association between Metscore and serum FAs. Results: The high-cardiovascular-risk group exhibited elevated values of HOMA-IR, palmitic, oleic, cis-vaccenic, and monounsaturated fatty acids, as well as the SCD-18C, indicating a heightened cardiovascular risk. Conversely, HDL-c, QUICK, gamma-linolenic, and eicosatetraenoic fatty acids showed lower values compared to the low-risk group. Conclusions: Women with severe obesity and high cardiovascular risk have lower values of some omega-3 and omega-6 FAs, considered cardioprotective and anti-inflammatory, and have higher lipogenic activity and FAs, correlated with high cardiovascular risk. These findings emphasize the need to address lipid metabolism in this population as a therapeutic target to reduce cardiovascular risk. Future research should explore clinical interventions that modulate fatty acid metabolism to mitigate cardiometabolic complications.

Association of serum fatty acids with bone health in rural elderly population in Qingdao, China: A cross-sectional study.

As a type of macronutrient, fatty acids (FA) play significant roles in the bone health of elderly people. However, the specific association between different types of FA and bone health is not fully understood, especially in rural elderly populations. To address this gap, a study was conducted in rural areas of Qingdao, China. Participants aged 65 and older were randomly recruited from 11 rural villages in Licha town, Qingdao City. The levels of serum FA in their serum were measured to investigate the associations between FA and bone mass. The results showed that levels of saturated fatty acids (SFA), n-3 polyunsaturated fatty acids (n-3 PUFA), and n-6 polyunsaturated fatty acids (n-6 PUFA) were all significantly associated with bone mass. Specifically, higher levels of SFA were positively correlated with low bone mass (LBM), while PUFA levels were inversely correlated with LBM. Furthermore, the odds ratio (OR) for LBM exhibited a significant nonlinear dose-response relationship (pnonlinearity = 0.1989) with SFA levels, and a significant nonlinear dose-dependent relationship was also observed with the levels of n-3PUFA and n-6PUFA (pnonlinearity = 0.6183, 0.5808, respectively), indicating that increasing dietary PUFA intake appropriately and controlling SFA intake may benefit the bone health of elderly individuals in rural areas.

Intriguing hepatoprotective effects of sucrose on hepatocellular carcinoma pathogenesis

Chronic liver disease is closely linked to dietary intake factors, such as high consumption of simple carbohydrates including sucrose. In this study, the influence of sucrose on the development of hepatocellular carcinoma (HCC), the most common primary liver malignancy, was explored. Using the hepatocarcinogen diethylnitrosamine (DEN) to induce HCC in the rat, we co-administered sucrose with DEN. The co-administration significantly modified body, liver and pancreas weight, as well as, serum fatty acids and triglycerides. DEN caused liver structural alteration, fibrosis, and tumor formation; surprisingly, co-administration with sucrose restored hepatic lipids, improved liver architecture, and reduced fibrosis and tumor development. Sucrose intake negatively regulated tumor markers and cell proliferation, and reduced the expression of genes associated with lipid metabolism and oxidative stress response. These findings highlight a hepatoprotective effect of sucrose during DEN-induced hepatocarcinogenesis, underlining an intriguing role of high sucrose consumption during HCC development and providing new insights as well as possible pathways of cellular protection under sucrose intake on hepatocarcinogenesis.

Associations of the rs12504538 and rs6824447 Polymorphisms of the Elovl6 Gene with Estimated Elongase and Desaturase Activity and Fatty Acid Concentrations in Mexican Women with Gestational Diabetes Mellitus

Background: This study aimed to investigate the possible associations of the rs12504538 and rs6824447 polymorphisms of the Elovl6 gene with estimated elongase and desaturase activity and saturated fatty acid concentrations in Mexican women with Gestational Diabetes Mellitus (GDM). Methods: We recruited 172 women in the second and third trimesters of pregnancy who had undergone an oral glucose tolerance test, including 66 who had diagnosed with GDM according to the 2016 ADA criteria and 106 who had normal glucose tolerance test results, from the General Hospital and Health Centers of the Health Ministry of Guanajuato, México. Participants were matched by gestational week. Data on age, gestational week and anthropometric characteristics were collected. Blood samples were drawn after an overnight fast for the measurement of serum glucose, lipid, NEFA, serum fatty acid and insulin levels; SNP genotyping and quantification of fatty acids was performed and elongase and desaturase activity was estimated. Findings: With the exception of HDL-cholesterol, all variables, including NEFA levels, were significantly greater in the GDM group than in the non-GDM group. The rs6824447 polymorphism of the Elovl6 gene, an age >25 years and HOMA-IR levels were associated with the development of GDM (OR=5.1, 95% CI 1.56-17.1, p=0.006; OR=4.89, 95% CI 1.65-14.4, p=0.003; OR=34.1 95% CI 8.7-133, p<0.000001, respectively). Palmitic acid (OR=1.08; 95% CI: 1.06-1.11; p<0.001) and oleic acid (OR=1.17; 95% CI: 1.14-1.2; p<0.001) concentrations were also associated with the development of GDM. No differences in the estimated elongase and desaturase activity among the non-GDM and GDM groups were found and only the activity of Δ9D SCD18 desaturase was marginally high in GDM patients (p=0.050). Conclusion: The rs6824447Elovl6 polymorphism is associated with the development of GDM, as are high serum palmitic acid, oleic acid and stearic acid concentrations and estimated Δ9D SCD18 desaturase activity.

Serum Fatty Acids and Inflammatory Patterns in Severe Obesity: A Preliminary Investigation in Women.

Background: Inflammation plays a central role in many chronic diseases that characterize modern society. Leptin/adiponectin and adiponectin/leptin ratios have been recognized as notable markers of dysfunctional adipose tissue and, consequently, an inflammatory state. Methods: Blood samples were collected from 41 adult volunteers (40.2 ± 8.3 years) diagnosed with severe obesity (BMI 46.99; 42.98-51.91 kg/m2). The adipokines were quantified using an enzyme-linked immunosorbent assay, while the serum fatty acid analysis was conducted using chromatography. Results: The results unveiled a positive correlation between the leptin/adiponectin ratio and the 20:3n6 fatty acid (r = 0.52, p = 0.001), as well as a similar positive correlation between the adiponectin/leptin ratio and the 22:6n3 fatty acid (r = 0.74, p = 0.001). In the regression analysis, the 22:6n3 fatty acid predicted the adiponectin/leptin ratio (β = 0.76, p < 0.001), whereas C20:3 n-6 was a predictor for inflammatory markers (β = 4.84, p < 0.001). Conclusions: In conclusion, the 22:6n3 fatty acid was demonstrated to be a predictive factor for the adiponectin/leptin ratio and C20:3 n-6 was a predictor for inflammatory markers. This discovery, novel within this population, can help develop new intervention strategies aimed at controlling the inflammatory status in individuals classified as having severe obesity.

Changes in serum fatty acid profile after laparoscopic sleeve gastrectomy

Changes in serum fatty acid profile after laparoscopic sleeve gastrectomy

The Long-Term Effect of Kidney Transplantation on the Serum Fatty Acid Profile

Background: Epidemiologic evidence has demonstrated the prevalence of metabolic disorders and increased cardiovascular risk related to lipid metabolism disorders in kidney transplant recipients. Therefore, it is of great importance to understand lipid alterations and to look for ways to reduce cardiovascular risk in this patient group. Methods: Our study included 25 patients with chronic kidney disease undergoing kidney transplantation (KTx). Three blood samples were taken from each patient: before KTx, 3 months after KTx and 6–12 months after KTx. A series of biochemical blood tests and a detailed analysis of the serum fatty acid profile were performed. Results: In our previous study, the effects of kidney transplantation on serum fatty acid (FA) profile 3 months after the procedure were investigated. The current study shows the longer-term (6–12 months) effects of the procedure on the serum FA profile. We found that although n-3 polyunsaturated FA levels started to decrease 3 months after surgery, they normalized over a longer period of time (6–12 months). Furthermore, we observed a strong decrease in ultra-long-chain FAs and an increase in odd-chain FAs over a longer time after kidney transplantation. All of the above FAs may have an important impact on human health, including inflammation, cardiovascular risk or cancer risk. Conclusions: The changes in serum FA profiles after kidney transplantation are a dynamic process and that more detailed studies could provide an accurate indication for supplementation with some FAs or diet modification.

Association of serum n-3 and n-6 docosapentaenoic acids with cognitive performance in elderly adults: National Health and Nutrition Examination Survey 2011–2014

Limited information exists on the influence of docosapentaenoic acid (DPA) on cognitive function. We investigated the association between serum n-3 and n-6 DPAs and cognitive performance in an elderly population from the National Health and Nutrition Examination Survey, 2011–2014. Restricted cubic spline and logistic regression analyses were utilized. A total of 1,366 older participants were included. Elevated proportions of DPA(n3) in total serum fatty acids were slightly associated with higher DSST scores (OR 0.61, 95% CI (0.38–0.97)), and higher proportions of DPA(n6) in total serum fatty acids were significantly associated with lower scores on different cognitive tests (CERAD (1.64, 1.02-2.65), AFT (2.31, 1.43- 3.75), DSST (3.21, 1.98-5.22) and global cognition (2.85, 1.74–4.66)). After multivariable adjustment, DPA(n3) exhibited no association with cognitive performance, whereas DPA(n6) remained correlated with AFT (1.98, 1.13–3.48), DSST (2.63, 1.43–4.82) and global cognition (2.15, 1.19–3.90). In stratified analyses, higher levels of DPA(n3) were associated with better performance in CERAD among participants aged ≥70, in DSST among those without diabetes and in global cognition among people with lower incomes. Increased DPA(n6) levels were associated with worse performance in AFT and DSST among those aged 60–70 and in all cognitive tests among those with better incomes. In conclusions, elevated levels of serum DPA(n3) may be beneficial for cognitive performance among elderly adults, especially in those over 70 years, with lower incomes and without diabetes. Serum n-6 DPA might be negatively associated with cognitive function, and this association is more pronounced among those who aged 60–70 with higher incomes.

Correlation of the Serum Fatty Acids with Cognitive Function: An NHANES 2011-2014 and Multivariate Mendelian Randomization Analysis.

The relationship between serum fatty acids and cognitive function has been the subject of extensive study. To analyze the relationship between serum fatty acids composition and cognitive function by NHANES database and multivariate Mendelian randomization (MR) analysis. A sub-cohort of 1,339 individuals with serum fatty acids and Digit Symbol Substitution Test (DSST) examinations from the 2011-2014 wave of the NHANES were analyzed using fully adjusted multiple linear regression models for associations between serum hydrolyzed fatty acid levels and cognitive function. Univariable and multivariable MR was used to analyze the correlation between 98 exposures related to serum fatty acids and cognitive function. Results from different database sources were combined using meta-analysis. The fully adjusted regression analysis showed that linoleic acid (LA), Omega 6, fatty acids (FAs), and LA/FAs were positively correlated with DSST. 27 exposures were included for univariate MR analysis. Ultimately, only 2 traits had IVW test p-values ranging between 0.0019 and 0.05, both of which were LA/FAs. The meta-analysis of univariate MR revealed that LA/FAs was positively associated with cognitive function (β: 0.040, 95% CI = 0.013-0.067, p = 0.0041). In multivariate MR analysis, after adjusting for education, ischemic stroke, and age, LA/FAs was positively independently associated with cognitive function (IVW β: 0.049, 95% CI = 0.021-0.077, p = 0.0006). The results of MVMR are well in line with the univariate results. Both the Cross-sectional observational analyses and MR-based studies supported a suggestive causal relationship between the serum ratio of Linoleic acid in fatty acids and cognitive function.

Population dietary-metabolic characteristics and mortality from major cardiovascular disease subtypes: the Seven Contries Study 60-year follow-up

Background and aimDuring the last few years, the Seven Countries Study of Cardiovascular Diseases (SCS) produced some new analyses dealing with the relationships of a dietary score, the pool of dietary fatty acids and serum cholesterol with major types of cardiovascular disease (CVD) mortality in 10 cohorts of 6 countries made of middle-aged men followed-up for 60 years until extinction. This sparse evidence is condensed here to provide a coherent view. Methods and resultsThe Mediterranean Adequacy Index (MAI, a dietary score whose high levels depict the characteristics of the Mediterranean Diet), was highly and significantly associated in an inverse way, at country levels, with the Atherogenicity (ATI) and the Thrombogenicity (THI) indexes that included a series of dietary fatty acids. These indexes were highly and significantly associated in a direct way with country baseline serum cholesterol levels. Countries with high serum cholesterol had largely higher death rates from coronary heart disease (CHD) and lower rates from other heart diseases of uncertain etiology and stroke. The reverse was observed in countries with low serum cholesterol. ConclusionThe chain of diet, dietary fatty acids and serum cholesterol seems to be responsible in various ways for the different distribution of major CVD mortality subtypes in extincted cohorts.

PSIX-6 Algal oil as an alternative source of docosahexaenoic acid in feline diets

Abstract The global demand for eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation by humans and their necessity in companion animal foods has raised questions related to environmental sustainability and nutrient content of fish oil. The combination of reported diminishing EPA and DHA content in fish oil and the forecasting of a significant decline in global fish stocks over the next decade make it critical to consider alternative sources of omega-3 fatty acids to reduce dependence on fish harvests. Cultured algal oil has been identified as a promising and viable alternative to fish-based oils. As such, the purpose of this study was to determine the inclusion level of algal oil in cat foods necessary to deliver the same serum concentrations of DHA provided from fish oil. Cats (n = 26) were first fed a control food formulated to avoid ingredients that contain long chain omega-3 fatty acids [ɑ-linolenic (ALA), EPA, and DHA] for 5 wk, to establish a baseline serum concentrations of these fatty acids. Cats were then randomized into two groups, and fed test foods containing either fish oil or algal oil in sequential increasing levels of DHA (0.2%, 0.4%, and 0.6%) for 5-wk periods each. Blood was analyzed for serum DHA and EPA concentrations after each of these feeding periods. A regression analysis was used to calculate a bioequivalence factor between fish oil and algal oil inclusion levels. There was no difference (P &amp;gt; 0.05) in intake or body weight between cats consuming diets containing algal oil or fish oil. Analysis of serum fatty acid concentrations showed that increasing fish and algal oil had no effect (P &amp;gt; 0.05) on serum linolenic acid, ALA, or arachidonic acid; however, increasing fish and algal oil did have an effect on DHA such that serum DHA was increased at similar rates as fish oil (P = 0.050) and algal oil (P = 0.026) levels were increased in the diet. Although increasing levels of fish and algal oil both increased serum EPA concentrations (P &amp;lt; 0.001), fish oil increased serum EPA to a greater extent than algal oil when fed at all levels. Overall, these data indicate that inclusion of algal oil is a good alternative dietary source of DHA, but less of EPA, and that algal oil will need to be added to the diet in higher concentrations to achieve similar serum EPA concentrations as fish oil.

Feeding sows milk biofortified with n-6 and n-3 modulates immune status of sows and drives positive transgenerational effects.

The risk of chronic diseases such as cardiovascular disease, cancer, inflammation, obesity, and autoimmune disease is linked to the quality of dietary fats, with lower intake of saturated and higher intake of n-6 and n-3 polyunsaturated fatty acids (PUFA) considered beneficial to health. This study investigated the effect of supplementing sows' diets with cow's milk biofortified with n-6 or n-3 PUFA, at varying n-6/n-3 ratios (8.26, 7.92, and 2.72) during their growing phase and throughout gestation and lactation on their reproductive performance and immune-inflammatory status. Specifically, we analyzed circulating cholesterol and fatty acid profiles of serum, colostrum and milk, sow body weight, and neonate colostrum intake, Apgar scores, muscle composition, and embryo viability. Analysis of circulating immunoglobulins (Ig), interleukins, and eicosanoids and complement system hemolytic activity were used to evaluate inflammatory and immune responses of sows and piglets. Expression of lipolysis and lipogenic genes in the liver were investigated in sows and piglets, with additional investigation of hypothalamus genes regulating appetite in sows. Feeding sows milk biofortified with n-6 and n-3 PUFA altered serum fatty acid profiles, reduced triglycerides (TG), increased embryo total number, increased early gestation backfat, and reduced colostrum IgG. Piglets of biofortified sow had higher circulating IgA, IgM and TNF-α, and lower IL-10. Sows fed n-3 biofortified milk had higher very low-density lipoproteins (VLDL) and TNF-α in circulation. Offspring from sows fed n-6 versus n-3 biofortified milk had lower IL-10 and expression levels of SREBP-1. N-3 versus n-6 also lowered arachidonic acid (ARA) levels in sow's milk and piglet viability 1. Findings offer insights into the potential health benefits of dietary supplementation with biofortified milk in swine, which serve as good model of diet-nutrition studies of humans, and therefore can potentially be considered in dietary recommendations both human and animal populations.

Impact of adding eicosapentaenoic and docosahexaenoic acid-rich fish oil in sow and piglet diets on blood oxylipins and immune indicators of weaned piglets

Weaning is a decisive event in piglets’ life. This study aimed to evaluate whether the inclusion of fish oil, rich in eicosapentaenoic and docosahexaenoic acids (EPA and DHA), in sow and piglet diets, increased the concentration of anti-inflammatory molecules in the blood of weaned piglets and whether the effect was dependent on the pigs being born with either low or a high birth BW (bBW). Thirty-six sows in four consecutive batches were randomly distributed between a control diet with animal fat (15 g/kg in gestation and 30 g/kg in lactation) or a n-3 long-chain fatty acid diet (LCFA; totally or half replacing animal fat by fish oil during gestation and lactation, respectively) from service until weaning (ca. 28 days). At birth, the two lightest (LBW) and the two heaviest (HBW) piglets in each litter were identified and, at weaning, grouped in pens by pairs prioritising their bBW. Pens were further distributed into a control (30 g/kg animal fat) or n-3 LCFA diet (totally replacing animal fat by fish oil) for 28 days. At the end of the trial, blood was collected from piglets in the first batch (n = 48). Serum fatty acids (FAs) were quantified by GC, plasma oxylipins by ultra-HPLC-MS, and plasma immune indicators by ELISA. An interaction between piglet diet and bBW for average daily gain (P = 0.020) and average daily feed intake (P = 0.014) during the whole postweaning indicated that dietary n-3 LCFA−promoted LBW piglets to have a similar growth and intake than HBW piglets reaching 1.5 kg average BW more at the end of the postweaning period than LBW control piglets. Fish oil in piglet diets also increased the concentrations of total n-3 FA, EPA and DHA (all P < 0.001), their resultant oxylipins, particularly their hydroxy derivatives from lipoxygenase enzymatic pathway (all P < 0.001) and tended to increase immunoglobulin M (P = 0.067) in blood. Regarding the bBW category, LBW piglets tend to increase tumour necrosis factor α in plasma (P = 0.083) compared to HBW. It is concluded that fish oil in postweaning diets could enhance the daily gain and feed intake of LBW piglets, increasing the concentration of serum n-3 FAs and their derived oxylipins in plasma.

Maternal cafeteria diet programs fecal microbiota and modulates serum fatty acid and amino acid levels in adulthood rats

Maternal food environment can program fecal microbiota in offspring mediated by the imprint of intrauterine conditions. Gut bacteria play a role in host fatty acid and amino acid metabolism. This study aimed to determine the effects of maternal diet on fecal microbiota, and the impact on fatty acid and amino acid metabolism in male offspring rats. Ten male pups from dams fed standard diet (C-C, n = 5) and cafeteria diet (Caf-C, n = 5) were fed standard chow diet for twenty-three weeks. Fresh fecal samples were collected at three and twenty-six weeks of age for fecal microbiota analysis by metagenomic sequencing of the V3-V4 region of the 16S rRNA gene. At the end of the study, serum samples were collected to analyse fatty acids from phospholipid and cholesterol ester fractions by gas chromatography and free amino acids by liquid chromatography. The bacterial abundance from the Actinobacteria and Proteobacteria phyla significantly decreased over time for both groups. Additionally, significant differences were found between C-C and Caf-C groups in these bacterial phyla. In the Caf-C group, Firmicutes and Elusimicrobia phyla increased, while Bacteroidetes decreases in adulthood samples. At the genus level, the abundance of Bacteroides decreased, while Elusimicrobium, Lactobacillus, Turicibacter, Blautia, and Veillonella increased in the Caf-C group. Several metabolites including PL-MCFAs (caprylic acid and capric acid), CE-MUFAs (palmitoleic acid and heptadecenoic acid), and free amino acids aspartate, glutamic acid, and cysteine were significantly higher in Caf-C group. This study underscores the putative programming of offspring fecal microbiota by maternal diet impact. These changes led to alterations fatty acids and amino acids metabolism in adult male offspring rats.

Nervonic acid triggered ovarian inflammation by inducing mitochondrial oxidative stress to activate NLRP3/ IL-1β pathway

IntroductionMetabolic syndrome is a serious public health concern across the globe. However, the typical metabolites and mechanisms underlying the decreased fertility related to metabolic syndrome is still elusive. ObjectivesThe aim of the present study was to explore the typical metabolites and mechanisms underlying the decreased fertility related with metabolic syndrome. MethodsUtilizing metabolomics, a comparative analysis was conducted on fatty acid compositions in various tissues of sows with high and low reproductive performance. Additionally, serum fatty acid compositions in a metabolic syndrome model (obese mice) induced by a high-fat diet (HFD) were investigated to elucidate the lipid metabolites associated with metabolic syndrome. Furthermore, the impact of nervonic acid (NA) on ovarian function was examined using rodent animal models (rats and mice). Through biological techniques such as transcriptomics, CUT&Tag, and analysis of post-translational protein modifications, the molecular mechanisms underlying NA mediated ovarian inflammation were further elucidated based on models utilizing ovarian granulosa cells from pigs, humans, and mice. Finally, validation was performed on ovaries from patients diagnosed with polycystic ovary syndrome. ResultsIn vitro, targeted serum lipidomic analysis revealed that sows with low embryo survival rates exhibited abnormal lipid metabolism characterized by abnormal accumulation of NA in the liver, ovary, and adipose tissue. Additionally, elevated NA levels trigger ovarian inflammation to cause ovarian dysfunction in both sows and rats. Mechanistically, NA induce mitochondrial oxidative stress through inhibiting respiratory chain proteins CYTB and NDFUB8 to activate NLRP3 inflammasome, which triggers procaspase-1 into active caspase-1, and convert the cytokine precursors pro-IL-1β into biologically active IL-1β in ovarian granulosa cells. Notably, we evidenced that NA promotes IL-1β activities by increasing H3K9ac modification level of IL-1β promoter regions and regulating the expression of the transcription factor AP-1. Finally, we found that the decreased expression of CerS2 in ovaries and the increased level of chemokine CXCL14 may be the cause of abnormal NA accumulation. Surprisingly, individuals with polycystic ovary syndrome, obesity, non-alcoholic fatty liver or gestational diabetes mellitus exhibit a high level of serum NA. ConclusionCollectively, our current study suggests that NA is a typical metabolite of metabolic syndrome, which strongly influences the ovarian function and embryo survival and also provides that interfering with mitochondrial ROS production is a potential strong strategy for target solving abnormal NA accumulation.

Fatty acid composition of blood serum and erythrocyte membranes in men with steatosis and steatohepatitis with normal transaminase activity

Aim. To study the characteristics of the fatty acid (FA) profi le of blood serum and erythrocyte membranes in patients with two forms of fatty liver disease (metabolic + alcoholic): steatosis and steatohepatitis with normal transaminase activity.Materials and methods. We examined 33 men (50.7 ± 9.6 years) with fatty liver disease (metabolic and alcoholic) with fi brosis F ≤ 1 (FibroTest). According to the ActiTest results, patients were divided into groups of steatosis – with minimal (A0–1) activity (n = 17) and steatohepatitis – with moderate/severe (A2–3) necroinfl ammatory activity (n = 16). The FA composition of blood serum and erythrocyte membranes was studied using gas chromatography/mass spectrometry Agilent 7000B (Agilent Technologies, Inc., USA). Methods of unpaired statistics using volcano plot and discriminant analysis based on orthogonal least squares (Orthogonal Partial Least Squares Discriminant Analysis, OPLS-DA), ROC analysis were applied.Results. Volcano plot analysis showed that in patients with fatty liver disease (metabolic and alcoholic) with normal transaminase activity, serum levels of stearic C18:0 (p = 0.016), arachidic C20:0 (p = 0.023), ratio saturated / polyunsaturated fatty acids (PUFA) (p = 0.001) were statistically signifi cantly higher in the steatohepatitis group compared with the steatosis group. The total content in the blood serum of all PUFA (p = 0.003), margaric C17:0 (p = 0.011), the sum of two omega-3 PUFA – eicosapentaenoic acid (C20:5n-3) and docosahexaenoic acid (C22:6n-3) (p = 0.04), the total content of all omega-3 PUFA (p = 0.042) were statistically signifi cantly lower in patients with steatohepatitis. OPLS-DA demonstrated fairly accurate separation of steatohepatitis and steatosis using individual FA and their ratios. When individual FA and their ratios were included in the analysis, a model was obtained with AUC = 0.827 (95% confi dence interval 0.499–1.0), sensitivity 82.2% and specifi city 80.7%.Conclusion. FA in blood serum and erythrocyte membranes appear to be promising biomarkers of steatohepatitis with normal levels of transaminases.

Serum Fatty Acid Profiles and Neurofilament Light Chain Levels in the General Population

BackgroundPrevious studies have demonstrated associations between fatty acids and neurological disorders. However, no studies have examined the relationship between serum fatty acid levels and serum neurofilament light chain (NfL), a biomarker of neurological disorders. ObjectivesThis study aimed to comprehensively investigate the intricate relationship between 30 serum fatty acids and serum NfL levels in a nationally representative sample of United States adults, using data from the 2013–2014 National Health and Nutrition Examination Survey. MethodsUsing a cross-sectional analysis, multivariable linear regression models were used to explore the associations between 30 serum fatty acids and serum NfL levels. This analysis involved adjustment for potential confounding variables, including age, sex, race, body mass index (BMI), smoking status, hyperlipidemia, and diabetes, to clarify the association between serum fatty acids and serum NfL levels. ResultsThe analysis revealed that certain fatty acids exhibited distinct associations with serum NfL levels. Notably, docosanoic acid (22:0) and tricosanoic acid (C23:0) were found to be inversely associated with serum NfL levels (β = −0.280, 95% confidence interval [CI]: −0.525, −0.035; β = −0.292, 95% CI: −0.511, −0.072). Conversely, palmitoleic acid (16:1n−7) demonstrated a positive association with serum NfL levels (β = 0.125, 95% CI: 0.027, 0.222). Notably, these associations remained significant even after adjustment for potential confounders. ConclusionsIndividuals with high relative concentrations of certain SFA exhibited decreased serum NfL, whereas those with high relative concentrations of certain monounsaturated fatty acids showed increased serum NfL. These findings contribute to a deeper understanding of the potential impact of serum fatty acids on NfL levels, shedding light on novel avenues for further investigation and potential interventions in the context of neurological health.

Excessive palmitic acid disturbs macrophage α-ketoglutarate/succinate metabolism and causes adipose tissue insulin resistance associated with gestational diabetes mellitus

Abnormal polarization of adipose tissue macrophages (ATMs) results in low-grade systemic inflammation and insulin resistance (IR), potentially contributing to the development of diabetes. However, the underlying mechanisms that regulate the polarization of ATMs associated with gestational diabetes mellitus (GDM) remain unclear. Thus, we aimed to determine the effects of abnormal fatty acids on macrophage polarization and development of insulin resistance in GDM. Levels of fatty acids and inflammation were assessed in the serum samples and adipose tissues of patients with GDM. An in vitro cell model treated with palmitic acid was established, and the mechanisms of palmitic acid in regulating macrophage polarization was clarified. The effects of excessive palmitic acid on the regulation of histone methylations and IR were also explored in the high-fat diet induced GDM mice model. We found that pregnancies with GDM were associated with increased levels of serum fatty acids, and inflammation and IR in adipose tissues. Increased palmitic acid could induce mitochondrial dysfunction and excessive ROS levels in macrophages, leading to abnormal cytoplasmic and nuclear metabolism of succinate and α-ketoglutarate (αKG). Specifically, a decreased nuclear αKG/succinate ratio could attenuate the enrichment of H3K27me3 at the promoters of pro-inflammatory cytokines, such as IL-1β, IL-6, and TNF-α, leading to cytokine secretion. Importantly, GDM mice treated with GSK-J4, an inhibitor of histone lysine demethylase, were protected from abnormal pro-inflammatory macrophage polarization and excessive production of pro-inflammatory cytokines. Our findings highlight the importance of the metabolism of αKG and succinate as transcriptional modulators in regulating the polarization of ATMs and the insulin sensitivity of adipose tissue, ensuring a normal pregnancy. This novel insight sheds new light on gestational fatty acid metabolism and epigenetic alterations associated with GDM.

Correlation between the Serum Fatty Acids and Insulin in Gestational Diabetes

Abstract Background: Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance that develops or is first recognized during pregnancy. Pregnancy is a diabetogenic condition marked by hyperinsulinemia and insulin resistance. In the early stages of pregnancy, maternal hormones enhance the production of insulin together with greater peripheral utilization, resulting in lower maternal blood sugar. Despite several research, the pathophysiology of GDM remains unknown, and the results acquired thus far point to a complicated process of interaction between multiple genetic, metabolic, and environmental variables. Methods: The aim of the present study was to find the correlation between serum fatty acid and insulin in GDM. Serum fatty acids were estimated by gas chromatography. Serum insulin levels were estimated using an enzyme-linked immunosorbent assay kit. Results: In the present study, we have collected serum samples from 50 pregnant women with GDM and normal pregnant women. We observed significantly increased levels of saturated fatty acids such as myristoleate and methyl palmitate, omega-3 fatty acids, α-linolenic acid, and omega-6 fatty acids, arachidonic acid. Conclusion: Alterations in plasma-free fatty acid (FFA) content or profile may contribute to insulin resistance. Furthermore, several FFAs can predict GDM in early pregnancy and are highly related to fetal growth and development, as well as the presence of macrosomia. Finally, proper fatty acid intake should be examined before and during pregnancy to optimize mother and newborn outcomes and introduce new preventive and therapeutic options for GDM.