Serum Fatty Acid Research Articles

Insulin Resistance and Pellino-1 Mediated Decrease in the Activities of Vasodilator Signaling Contributes to Sunitinib-Induced Hypertension.

Antiangiogenic tyrosine kinases inhibitors induce hypertension, which may increase the incidents of cardiovascular complications and limit their use. However, the mechanisms by which usage of TKIs results in hypertension have not been fully understood. Here, we report the potential mechanisms of how sunitinib, a widely used TKI, induces hypertension. Male SD rats were randomly divided into control group and sunitinib-administrated group. We show that sunitinib administration for seven days caused a significant increase in artery blood pressure, along with glycerolipid metabolism abnormalities including decreased food intake and low body weight, hypoglycemia, hyperinsulinemia. Sunitinib administration also resulted in a significant increase in the levels of insulin autoantibody (IAA), cyclic adenosine monophosphate and free fatty acid in serum; whereas, sunitinib administration had no effects on serum glucagon levels. Sunitinib led to the decreased insulin sensitivity as determined by insulin tolerance test (ITT) and glucose tolerance test (GTT), reflecting insulin resistance occurred in sunitinib-treated rats. The results obtained from wire myograph assay in the mesenteric arteries show that endothelium-dependent relaxation, but not endothelium-independent relaxation, was impaired by sunitinib. Furthermore, western blot analysis revealed that the expressions levels of phosphorylated IRS-1, Pellino-1, AKT and eNOS were significantly attenuated by sunitinib in rat mesenteric artery tissues and in the sunitinib-treated primary cultured mesenteric artery endothelial cells. The levels of serum and endothelium-derived nitric oxide were also significantly decreased by sunitinib. Moreover, sunitinib-induced decrease in the expression levels of phosphorylated AKT and eNOS was further reduced by knocking down of Pellino-1 in MAECs. Our results suggest that sunitinib causes vascular dysfunction and hypertension, which are associated with insulin resistance- and Pellino-1-mediated inhibition of AKT/eNOS/NO signaling. Our results may provide a rational for preventing and/or treating sunitinib-induced endothelial dysfunction and hypertension.

Time-of-day effects of consumption of fish oil–enriched sausages on serum lipid parameters and fatty acid composition in normolipidemic adults: A randomized, double-blind, placebo-controlled, and parallel-group pilot study

ObjectivesThe body clock controls diurnal rhythms of nutrient digestion, absorption, and metabolism. Fish oil (FO) contains abundant ω-3 polyunsaturated fatty acids (PUFA), including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), that are thought to lower triglyceride (TG) levels. This randomized, placebo-controlled, double-blind, parallel-group trial aimed to confirm the effects of the time of FO intake on TG in healthy Japanese adults. MethodsTwenty healthy Japanese adults (age, 20–60 y) were assigned to either a group that consumed sausages enriched with FO (DHA 1010 mg; EPA 240 mg) in the morning and a placebo (DHA 40 mg; EPA 15 mg) in the evening (BF-FO) or another group that consumed FO-enriched sausages in the evening and the placebo in the morning (DN-FO). Serum lipid parameters, fatty acid (FA) composition, and messenger RNA expression of lipogenic genes in circulating blood cells were evaluated in fasting blood samples before, as well as after 4 and 8 wk of FO intake. ResultsSerum concentrations of TG and total saturated FA were significantly decreased in the BF-FO group, whereas those of ω-3 PUFA were significantly and identically increased in both groups. Serum concentrations of ω-6 PUFA were significantly decreased in the BF-FO but not the DN-FO group. Messenger RNA expression of the lipogenic genes ACLY, SCD, and FASN were similarly reduced in both groups. ConclusionsThese findings suggested that the timing of FO intake affects both serum FA concentrations and TG metabolism in normolipidemic humans. The mechanisms of these effects of FO on lipid metabolism require further investigation.

Fatty acids and osteoarthritis: the MOST study

Inflammation worsens joint destruction in osteoarthritis (OA) and aggravates pain. Saturated and n-6 fatty acids (FAs) increase, whereas n-3 FAs reduce inflammation. We examined whether FA levels affected the development of OA. We studied participants from the Multicenter Osteoarthritis study (MOST) at risk of developing knee OA. After baseline, repeated knee x-rays and MRIs were obtained and knee symptoms queried through 60 month follow-up. Using baseline fasting samples, serum FAs were analyzed with standard assays. After excluding participants with baseline OA, we defined two sets of cases: those developing radiographic OA and those developing symptomatic OA (knee pain and radiographic OA). Controls did not develop these outcomes. Additionally, we examined worsening of MRI cartilage loss and synovitis and of knee pain using WOMAC and evaluated the number of hand joints affected by nodules. In regression models, we tested the association of each OA outcome with levels of saturated, n-3 and n-6 FAs adjusting for age, sex, BMI, education, race, baseline pain and depressive symptoms. We studied 260 cases with incident symptomatic and 259 with incident radiographic OA. Mean age was 61 years (61% women). We found no signficant nor suggestive associations of FA levels with incident OA (e.g., for incident symptomatic OA, OR per s.d. increase in n-3 FA 1.00 (0.85, 1.18) nor with any OA outcome in knee or hand. Despite previously described effects on systemic inflammation, blood levels of FAs were not associated with risk of later knee OA or other OA outcomes.

Effect of Blueberry Anthocyanin-Rich Extracts on Peripheral and Hippocampal Antioxidant Defensiveness: The Analysis of the Serum Fatty Acid Species and Gut Microbiota Profile.

The current study investigated the positive effects of blueberry anthocyanin-rich extracts (BAE) on either peripheral or hippocampal antioxidant defensiveness and established the connection of the improved antioxidant status with the altered fatty acid species and gut microbiota profile. High-fat diet-induced oxidative stress in C57BL/6 mice was attenuated by BAE administration, which was reflected by strengthened antioxidant enzymes, alleviated hepatic steatosis, and improved hippocampal neuronal status. Serum lipidomics analysis indicated that the fatty acid species were altered toward the elevated unsaturated/saturated ratio, along with phospholipid species toward enriched n-3 polyunsaturated fatty acid compositions. The modulated antioxidant pattern could be attributed to the increased bacteria diversity, stimulated probiotics (Bifidobacterium and Lactobacillus) and short-chain fatty acid (SCFA) producers (Roseburia, Faecalibaculum, and Parabacteroides) improved by anthocyanins and their metabolites, which improved the colon environment, characterized by promoted SCFAs, restored colonic mucosa, and reorganized microbial structure. Thus, anthocyanin-rich dietary intervention is a promising approach for the defensiveness in human oxidative damage and neurodegeneration.

Analysis of Serum Fatty Acids Profile in Kidney Transplant Recipients

Patients with end-stage kidney disease, treated with renal transplantation, are at increased risk of cardio-vascular disease (CVD) and cardio-vascular mortality. They are also characterized by an atherogenic dyslipidemia. Alterations of the fatty acids (FA) profile contribute to increased cardio-vascular risk in the general population. In the current study we test the hypothesis that kidney transplantation is associated with ab-normalities in FA profile. FA profile was analysed by gas chromatography–mass spectrometry in 198 renal transplant recipients, and 48 control subjects. The most profound differences between renal transplant patients and controls were related to the content of branched chain FA, monounsaturated FA, and n-6 polyunsaturated FA, respectively. The FA profile significantly separated the patients from the controls in the principal component analysis (PCA). The abnormalities of FA profile showed a tendency for normalization in long-term kidney recipients, as compared to patients with recent transplants. The n-3 PUFA content demonstrated a strong inverse association with the presence of inflammation. Most profound alterations of the FA profile were observed in patients with impaired graft function (glomerular filtration rate < 45 mL/min). The study demonstrated significant disorders of the FA profile in kidney transplant recipients, that might contribute to cardio-vascular risk in this vulnerable patient population.

Динаміка клінічних симптомів й функціонального стану біліарної системи у хворих на хронічний безкам’яний холецистит на тлі цукрового діабету 2 типу під впливом комплексної терапії

The urgent problem of modern medical science and practice is the rapid increase of comorbid pathology spreading among the population of the whole world. Among the nosological forms, which are quite often combined with each other, there are cardiovascular system, digestive tract and endocrine diseases, namely type 2 diabetes mellitus. Diseases of the biliary tract, in the form of chronic acalculous cholecystitis, occur in patients with type 2 diabetes more often than in its absence. There is no doubt that the combination of diseases of the gallbladder and type 2 diabetes significantly affects the course and prognosis of both diseases, and the development of complications is one of the main causes of disability and mortality in patients. In this regard, the priority areas of health protection are the search for preventive measures to eliminate the development of diseases, their complications and the amendment of therapeutic patterns. The purpose of the study was to evaluate the efficacy of complex therapy with the addition of ursodeoxycholic acid and alpha-lipoic acid in patients with concomitant chronic acalculous cholecystitis and type 2 diabetes on the basis of studying the dynamics of clinical symptoms and the content of bile acids in blood serum, as well as parameters of cholecystosonography (in overview and dynamic versions). Material and methods. In the course of the study, 62 patients with the combined course of chronic hepatitis and diabetes mellitus were examined. The age of the patients ranged from 44 to 75 years old. The duration of type 2 diabetes was from 1 to 19 years. The group was representative in terms of age and number of male and female probands. Upon admission to the hospital, all patients underwent a thorough examination using generally accepted clinical, laboratory and instrumental studies. Results and discussion. The complex treatment included hypoglycemic drugs, medical nutrition, prescription of antispasmodic and antibacterial therapy, ursodeoxycholic acid drugs at a dose of 15 mg / kg / day for 4 weeks, as well as preparations of alpha-lipoic acid 600 I / V drip for 10 days, followed by oral administration in within 12 weeks. In order to assess the effectiveness of therapy, clinical symptoms, serum levels of fatty acids, indicators of survey and dynamic cholecystosonography were evaluated after 3 months in the dynamics of treatment. Conclusion. The study showed that the addition of ursodeoxycholic acid and alpha-lipoic acid to the complex therapy was accompanied by positive effects due to an improvement in the contractility of the gallbladder, a decrease in the serum fatty acid content, improved the motor and cholesecretory functions of the gallbladder and the clinical condition of patients by eliminating abdominal pain and reducing the percentage of patients with chronic acalculous cholecystitis and type 2 diabetes with manifestations of dyspeptic, neuro-vegetative and asthenic syndromes

Serum fatty acids and risk of developing islet autoimmunity: A nested case-control study within the TRIGR birth cohort.

Circulating fatty acids have been linked to development of type 1 diabetes. To study the prospective associations of serum fatty acids with the risk of islet autoimmunity in high-risk children. A nested case-control selection was carried out within the TRIGR cohort, which included infants with HLA (DQB1 or DQA1)-conferred disease susceptibility and a first-degree relative with type 1 diabetes, born between 2002 and 2007 in 15 countries and followed-up until 2017. The present study included 244 case children positive for at least two islet autoantibodies (ICA, IAA, GADA, and IA-2A) and two control children were matched for country and age. Proportions of 26 serum fatty acids at cord blood and at 6, 12, and 18 months of age were assessed using gas-chromatography. The average proportions of the following fatty acids were associated with an increased risk of islet autoimmunity, adjusted for sex, HLA risk, and maternal type 1 diabetes: pentadecanoic acid (15:0) (OR 3.41: 95% CI 1.70, 6.85), heptadecanoic acid (iso 17:0) (2.64: 1.62, 4.28) and (anteiso 17:0) (2.27: 1.39, 3.70), stearic acid (18:0) (23.8: 2.32, 244.6), and conjugated linoleic acid (18:2n-7) (2.60: 1.47, 4.59). Breastfeeding and not having maternal type 1 diabetes were positively associated with levels of the above-mentioned fatty acids. N-3 fatty acids were not consistently associated with islet autoimmunity. We found direct associations of pentadecanoic acid, heptadecanoic acid, stearic acid, and conjugated linoleic acid with the risk of islet autoimmunity. Further studies are needed to understand the complex role of fatty acids in the development of type 1 diabetes.

Serum Fatty Acid Latent Classes Are Associated With Suicide in a Large Military Personnel Sample.

Fatty acids (FAs) are involved in the functioning of biological systems previously associated with suicidal behavior (eg, monoamine signaling and the immune system). We sought to determine (1) whether observed FA levels in a sample of military suicide decedents and living matched controls were consistent with latent classes having distinctive FA profiles and (2) whether those latent classes were associated with suicide and mental health diagnoses. Serum samples from 800 US military suicide decedents who died between 2002 and 2008 and 800 demographically matched living controls were selected at random from a large military serum repository and assayed for 22 different FAs. A latent class cluster analysis was performed using values of 6 FAs previously individually associated with suicide. Once the latent classes were identified, they were compared in terms of suicide decedent proportion, demographic variables, estimated FA enzyme activity, diagnoses, and mental health care usage. A 6-latent class solution best characterized the dataset. Suicide decedents were less likely to belong to 2 of the classes and more likely to belong to 3 of the classes. The low-decedent classes differed from the high-decedent classes on 9 FAs and on estimated indices of activity for 3 FA enzymes: 14:0, 24:0, 18:1 n-9, 24:1 n-9, 22:5 n-3, 22:6 n-3, 20:2 n-6, 20:4 n-6, 22:5 n-6, elongation of very long chain fatty acids protein 1 (ELOVL1), ELOVL6, and Δ9 desaturase. The FA profiles of the latent classes were consistent with biological abnormalities previously associated with suicidal behavior. This study suggests the utility of methods that simultaneously examine multiple FAs when trying to understand their relationship with suicide and psychiatric illness.

Metabolic profiling of fatty acids in Tripterygium wilfordii multiglucoside- and triptolide-induced liver-injured rats.

Tripterygium wilfordii multiglucoside (TWM) is a fat-soluble extract from a Chinese herb T. wilfordii, that’s used in treating rheumatoid arthritis, nephrotic syndrome and other skin diseases. Triptolide (TP) is a major active component in TWM. However, clinical applications of TWM are limited by its various toxicities especially hepatotoxicity. In recent studies, it has been reported that drug-induced liver injury (DILI) could induce the disorder of lipid metabolism in animals. Hence, this study focuses on the metabolic profile of fatty acids in TWM- and TP-induced liver-injured rats. In serum and liver tissue, 16 free and 16 esterified fatty acids were measured by gas chromatography coupled with mass spectrometry. Metabolic profile of serum fatty acids in rats with liver injury was identified by multivariate statistical analysis. The fatty acid levels in the serum of TWM- and TP-treated rats significantly decreased, whereas those in the liver tissue of TWM- and TP-treated rats obviously increased when compared with the vehicle-treated rats. Four free fatty acids were identified as candidate biomarkers of TWM- and TP-induced liver injury. Therefore, the targeted metabolomic method may be used as a complementary approach for DILI diagnosis in clinic.

Imidazoline Gemini Surfactants as Corrosion Inhibitors for Carbon Steel X70 in NaCl Solution.

The Gemini imidazoline surfactants were synthesized from a series of saturated fatty acids. Electrochemical impedance spectroscopy (EIS), polarization curve, and quantum chemistry methods were used to study the corrosion inhibition behavior of Gemini imidazoline surfactants for X70 carbon steel in NaCl solution. Results reveal that such kind of surfactants has an outstanding inhibition effect on carbon steel X70 in NaCl solution and that the restrained efficiency of Gemini imidazoline in an alkaline solution is better than that in a neutral solution. The shorter the carbon chain length, the higher the suppressive efficiency. The higher the concentration of Gemini imidazoline surfactant, the better the inhibition effect.

Serum fatty acid synthase levels and n-3 fatty acid intake in patients with breast cancer.

Fatty acid synthase (FASN) is a key enzyme in fatty acid biosynthesis that is usually over-expressed in patients with breast cancer, but its relationship with the patient's dietary habit is not clear. A higher intake of n-3 polyunsaturated fatty acids is related to reduced breast carcinogenesis invitro and invivo. The aim of this study was to clinically investigate the association between serum FASN levels and fatty acid intake in women newly diagnosed with breast cancer. In a case-control cross-sectional study, with 18 breast cancer patients and 29 controls, we evaluated nutritional status, dietary intake, and serum FASN levels. Statistical analyses were carried out with parametric and non-parametric tests, according to the sample's normality distribution. The mean age of breast cancer group (n=18) and control group (n=29) was 46.8±9.7y and 44.4.±8.6y, respectively. Mean serum concentration of FASN in breast cancer group was significantly higher (132.51±95.05ng/mL) than in control group (36.88±20.87ng/mL) (p<0.0001). Among breast cancer group, serum FASN levels of premenopausal women were significantly higher than those of postmenopausal women (p=0.026). There was no significant difference between the early and late disease stages in regard to serum FASN levels in breast cancer group. Mean nutrient intake was similar and n-3 docosahexaenoic acid intake was low in both groups. We observed no association regarding fatty acid intake and serum FASN levels. These data suggest that dietary n-3 fatty acid has no association with serum FASN levels among newly diagnosed breast cancer patients.

Complex patterns of circulating fatty acid levels in gestational diabetes mellitus subclasses across pregnancy

To investigate the relationship between maternal serum fatty acid levels and gestational diabetes mellitus (GDM) subtypes across pregnancy. A total of 680 singleton mothers enrolled in the Complex Lipids in Mothers and Babies (CLIMB) study in Chongqing, China were included. Clinical information and serum samples were collected at gestational weeks (GWs) 11-14, 22-28, and 32-34. 75g Oral Glucose Tolerance Test (OGTT) was conducted at GW 24-28 and GDM subtypes divided into three groups using International Association of Diabetes and Pregnancy Study Group (IADPSG) guidelines criteria: elevated fasting plasma glucose (FPG group; n=59); 1-h and/or 2-h post-load glucose (1h/2h-PG group; n=94); combined group (FPG&1h/2h-PG group; n=42). Non-GDM pregnancies were included (n=485) as controls. Twenty fatty acids were quantified in serum using gas chromatography-mass spectrometry (GC-MS) analysis. Overall, most serum fatty acid concentrations increased rapidly from the first to second trimester, followed by a plateauing or reduction in the third trimester (p<0.001). In cross sectional analysis, fatty acid concentrations were significantly higher in the FPG group at GW 11-14 and decreased in the 1h/2h-PG group at GW 32-34, relative to controls. Moreover, higher α-linolenic acid (ALA; the second tertile: adjusted odds ratio [aOR]=2.53, 95% CI: 1.17 to 5.47; the third tertile: aOR=2.60, 95% CI: 1.20 to 5.65) and docosahexaenoic acid (DHA; the second tertile: aOR=2.34, 95% CI: 1.10 to 4.97; the third tertile: aOR=2.16, 95% CI: 1.00 to 4.63) were significantly associated with a higher risk of GDM in women with elevated fasting plasma glucose at GW 11-14 (first tertile as reference). Our findings highlight the importance of considering GDM subtypes for the individualised management of GDM in pregnancy. ALA and DHA in early pregnancy are associated with a higher risk of FPG-GDM subtype. This has widespread implications when recommending n-3 PUFAs supplementation for women with GDM.

Validation of milk mid-infrared spectroscopy for predicting the metabolic status of lactating dairy cows in Australia

Increased concentrations of some serum biomarkers are known to be associated with impaired health of dairy cows. Therefore, being able to predict these biomarkers, especially in the early stage of lactation, would enable preventive management decision. Some health biomarkers may also be used as phenotypes for genetic improvement for improved animal health. In this study, we validated the accuracy and robustness of models for predicting serum concentrations of β-hydroxybutyrate (BHB), fatty acids, and urea nitrogen, using milk mid-infrared (MIR) spectroscopy. The data included 3,262 blood samples of 3,027 lactating Holstein-Friesian cows from 19 dairy herds in Southeastern Australia, collected in the period from July 2017 to April 2020. The models were developed using partial least squares regression and were validated using 10-fold random cross-validation, herd-year by herd-year external validation, and year by year validation. The coefficients of determination (R2) for prediction of serum BHB, fatty acids, and urea obtained through random cross-validation were 0.60, 0.42, and 0.87, respectively. For the herd-year by herd-year external validation, the prediction accuracies held up comparatively well, with R2 values of 0.49, 0.33, and 0.67 for of serum BHB, fatty acids, and urea, respectively. When the models were developed using data from a single year to predict data collected in future years, the R2 remained comparable, however, the root mean squared errors increased substantially (4-10 times larger than compared with that of herd-year by herd-year external validation) which could be due to machine differences in spectral response, the change in spectral response of individual machines over time, or other differences associated with farm management between seasons. In conclusion, the mid-infrared equations for predicting serum BHB, fatty acids, and urea have been validated. The prediction equations could be used to help farmers detect cows with metabolic disorders in early lactation in addition to generating novel phenotypes for genetic improvement purposes.

Abnormalities of Serum Fatty Acids in Children With Henoch-Schönlein Purpura by GC-MS Analysis.

Purpose: The objectives of this work were to test the levels of serum medium- and long- chain fatty acids (MLCFAs) in children and to discover their possible relationship with Henoch-Schönlein Purpura (HSP), also known as Immunoglobulin A vasculitis.Methods: A total of 57 children with HSP (HSP group) and 28 healthy children (CON group) were recruited for this study. Serum specimens were collected to detect the compositions and contents of MLCFAs by gas chromatography with mass spectrometry (GC-MS) analysis.Results: The contents of all detected 37 MLCFAs in the HSP group were higher than the healthy group. Thirty-one species of MLCFAs were discovered to have a significant difference (p < 0.05) in two groups. Comparing to healthy controls, there were 31, 31, 18 fatty acids showed a statistical difference in the untreated group, regular treated group, and withdrawal group of HSP, respectively. The trend of fatty acids in the three HSP groups was similar to the healthy controls, as well as the untreated group and regular treated group changed more obviously than the withdrawal group. Almitate (C16:0) and 18 carbon atoms (C18) of fatty acids were abundant in all three HSP groups, divided according to the treatment of glucocorticoid. Some fatty acids were found having considerable differences (p < 0.05) in three groups. Monounsaturated fatty acids (MUFAs), including elaidate (C18:1T), cis-11,14,17-eicosatrienoic acid ester (C20:1), and cis-15-tetracosenoate (C24:1), were distinctly higher in HSP children with renal damage.Conclusion: Our study revealed that the abnormalities in MLCFA may be associated with the development of HSP. Another interesting finding was that fatty acids contents were changing during the glucocorticoid treatment. Meanwhile, long-chain MUFAs may have an impact on renal damage in HSP patients. Further studies need to be carried out in order to explore the specific mechanism of fatty acids in the course of HSP.

In silico exploration of bioavailability, druggability, toxicity alerts and biological activity of a large series of fatty acids

This article explores in silico some physicochemical and electronic properties (partition coefficient, solubility, toplogical polar surface area TPSA, softness and polarizability), general Drug-likeness DL and specific druglikeness scores (G protein-coupled receptorsactivity GPCR, ion channel modulation ICM, kinase inhibition activity KI, nuclear receptor ligand activity NLR, Protease Inhibition PI, Enzyme Inhibitor EI drug scores), toxicity alerts (mutagenicity, tumorigenicity, irritation and reproduction) and Antimicrobial and antioxidant activities, for a large series of 47 fatty acids containing saturated fatty acids (24 SFA), monounsaturated fatty acids (11 MUFA) and polyunsaturated fatty acids (12 PUFA). The results obtained have clarified for each fatty acid its degree of bioavailability, druggability, the toxicity hazard and biological activity for its use therapeutically, cosmetically as well as nutritional product. SFA-1-5 and MUFA-25 met Log P and Nrot criteria, SFA-1-5, MUFA-24 and MUFA-25 met Log S criteria. Moreover, all the studied compounds felt within Mw, HA, HD and TPSA criteria, while only MUFA-25, PUFA-42, PUFA-43 and PUFA-46 had a reasonable DL. On the other hand, except SFA-1-4,7,8,11 and MUFA-27, the remaining fatty acids didn’t present any toxicity alert. Therefore, MUFA-25 is the most favorable according to bioavailability, druggability and the toxicity alerts.

Suppressive effects of mead acid supplementation on acute liver damage derived from green tea extract

〈Background〉 We reported on the characteristics of green tea extract (GTE)-induced hepatotoxicity in rats. Using this model, we explored the inhibitory effects of n-9 PUFA, mead acid (MA), by dietary supplementation. 〈Methods〉 7-week-old male Sprague-Dawley rats received a single intraperitoneal injection of 200 mg/kg GTE, serum and liver were collected 24, 48 hrs, and 7 days after the GTE injection. The control or 4.8% MA diets was given from one week before GTE injection to sacrifice. Control diet + saline, 4.8% MA diet + saline, control diet + GTE, and 4.8% MA diet + GTE groups were set. Serum biomarkers of hepatotoxicity [aspartate aminotransferase (AST), alanine aminotransferase (ALT)], liver histopathology, and immunohistochemistry of apoptosis (γH2A.X), oxidative stress (8-nitroguanosine) and hypoxia [hypoxia inducible factor (HIF)-1α] were examined. Fatty acid in serum and liver tissue of the control diet + saline and 4.8% MA diet+ saline groups were analyzed. 〈Results〉 In the control diet + GTE group, AST and ALT levels increased. Centrilobular hepatocellular necrosis was seen 24 and 48 hrs after GTE exposure. Furthermore, the levels of these changes decreased in the MA diet group. In the control diet + GTE group, γH2A.X, 8-nitroguanosine, and HIF-1α-positive hepatocytes appeared and peaked at 48 hrs. The level of these changes reduced by MA diet feeding. MA composition in the serum and liver significantly increased in the MA diet group, compared to the control diet group. 〈Conclusion〉The levels of GTE-induced liver damage, such as serum biomarkers, histology, and immunohistochemistry for hepatotoxicity were inhibited by MA diet feeding. This effect may be related to suppression of cell death via the pathway of oxidative stress and hypoxia in the liver.

Parental dietary arachidonic acid altered serum fatty acid profile, hepatic antioxidant capacity, and lipid metabolism in domestic pigeons (Columba livia).

The aim of this study was to explore the effects of dietary arachidonic acid on serum fatty acid profile, hepatic antioxidant capacity, and lipid metabolism in pigeon squabs by supplementing arachidonic acid in their parental diets. A completely randomized design was conducted consisting of control group, 0.05% dietary arachidonic acid supplementation group, 0.1% dietary arachidonic acid supplementation group, and 0.2% dietary arachidonic acid supplementation group. Six randomly selected squabs from each group were sampled on Day 21 post-hatch. Results indicated that moderate level (0.05%) of arachidonic acid in parental diets for pigeon squabs improved lipid metabolism via regulation on serum lipid profile and fatty acid composition and tended to reduce hepatic lipid accumulation in the premise of negligible damage to antioxidant status. Unfortunately, excessive parental supplementation of dietary arachidonic acid might be harmful to squab health. The regulatory effects of arachidonic acid were sensitive to the arachidonic acid doses. In conclusion, parental dietary arachidonic acid at 0.05% could be beneficial for squabs to maintain health as reflective aspects in ameliorative serum lipid profile, fatty acid composition, and reduced hepatic lipid accumulation.

Effects of feed restriction and supplementary garlic oil on blood metabolites in ewes.

The effects of garlic oil (GO) on serum fatty acids, lipid profiles and energy-related blood metabolites in feed-restricted fat-tailed ewes were investigated. For this purpose, twenty-eight dry, non-pregnant Makuei ewes (about three years of age; 45.00 ± 2.20 kg of body weight) were assigned randomly to four experimental groups including group 1 receiving basal diet as total mixed ration (TMR) without GO supplementation (control group), group 2 receiving 100% basal diet supplemented with GO (10.00 mg kg-1 BW), group 3 receiving 70.00% basal diet without GO supplementation and group 4 receiving 70.00% basal diet supplemented with GO (10.00 mg kg-1 BW). The main experimental period started eight weeks after performing adaptation and dietary allocations. Feed restriction reduced serum glucose levels along with higher serum levels of non-esterified fatty acids, triacylglycerols, β-hydroxybutyrate, low-density lipoprotein cholesterol, total cholesterol and very low-density of lipoprotein. Following feed restriction, the serum palmitic and oleic acids concentrations were increased. Garlic oil supplementation had a desirable effect on feed-restricted animals through lowering serum BHB and palmitic and oleic acids concentration and increasing the high-density lipoprotein cholesterol levels in the serum. These findings demonstrated that GO had the potential to reduce body-fat mobilization, thereby lowering the risk factors for disorders associated with negative energy balance in underfed ewes in the periparturient period.

Targeted Metabolomics Profiles Serum Fatty Acids by HFD Induced Non-Alcoholic Fatty Liver in Mice Based on GC-MS

Nonalcoholic fatty liver (NAFLD) is associated with metabolic abnormalities and changes in lipid processing. Fatty acids (FAs) are important signaling molecules in the body and are the main raw materials for lipid synthesis. To explore the lipidomic profile of serum fatty acids in mice, we put the mice on a high-fat diet (HFD) to induce NAFLD. We applied a targeted metabolic analysis approach using gas chromatography mass spectrometry (GC-MS) and established a method for simultaneous determination of 36 medium and long-chain fatty acids in the serum of mice. This method was validated for linearity, range, limit of detection (LOQ), limit of quantification (LOD), precision, accuracy, and recovery. The levels of most FA species and total FAs were increased in the HFD group (n=9) compared with the lean group (n=9). The principal component analysis (PCA) and the orthogonal partial least squares discriminant analysis (OPLS-DA) of all FA species were analyzed in both groups. We found that palmitic acid (16:0), stearic acid (18:0), oleic acid (18:1), and arachidonic acid (20:4) were significantly different (VIP＞1, p＜0.05 and FC＞1.5) in the two groups. We also calculated serum indices measure the activities of different enzymes involved in fatty acid metabolism. The de novo lipogenesis index, elongase index, n-6 FAs, saturated FAs, unsaturated FAs, and SCD1 index 2 were increased in the HFD group compared with the lean group while the n-3 FAs, n-3/n-6 of the index, and SCD1 index 1 were decreased in the HFD group compared with the lean group. Relationships between major FA species and biochemical indicators (LDL-C, TC, TG, ALT, and AST) were evaluated by Pearson analysis. The serum FA concentrations (C16:0, C18:0, C18:1, and C20:4) and serum indices ( De novo lipogenesis index, elongase index, saturated FAs, unsaturated FAs and n-6 FAs) positively correlated with LDL-C, TC, TG, ALT, and AST. Collectively, our study provides insights into NAFLD and its effect on lipid metabolism.

Lipid profile disturbances may predispose psoriatic patients to liver dysfunction.

IntroductionPsoriasis is a chronic inflammatory disease associated with metabolic disturbances and liver dysfunction. Both serum fatty acids (FA) and ceramides (Cer) have structural functions but also are signal molecules that could be involved in the pathogenesis of liver dysfunction.AimTo assess the concentration of the circulating FA and Cer in correlation with the alanine aminotransferase (ALT) blood level in psoriatic patients. In addition, we have examined the relationship between ALT concentration and severity of the disease and inflammation markers.Material and methodsEighty-five patients with psoriasis and 32 healthy controls were enrolled in the study. Patients were divided into 2 groups according to ALT blood levels. Serum concentration of 14 FA and 14 Cer were measured by gas-liquid chromatography. The results were correlated with the Psoriasis Area and Severity Index (PASI), serum lipid profile, and inflammatory markers.ResultsWe observed higher PASI score (p = 0.01) and higher C-reactive protein (p = 0.02) concentration in the group of psoriatic patients with high ALT. Serum ALT positively correlated with saturated fatty acids (SFA) (p = 0.01, r = 0.27) and SFA/unsaturated fatty acids (UFA) ratio (p = 0.01, r = 0.26). ALT negatively correlated with UFA level (p = 0.008, r = –0.28). Lignoceric ceramide positively correlated with ALT level (r = 0.22; p = 0.045) in psoriatic patients.ConclusionsPatients with severe psoriasis are predisposed to the development of liver dysfunction. We have demonstrated disturbances of serum fatty acid and sphingolipid profile in psoriatic patients, which may trigger liver disease.