Serum Free Fatty Acid Levels Research Articles

Synergistic association of elevated serum free fatty acid and glucose levels with large arterial stiffness in a general population: The Nagahama Study

BackgroundPrevious studies have reported that artificial increases in circulating free fatty acid (FFA) levels might have adverse effects on the vasculature. However, whether or not this effect can be extrapolated to physiological variations in FFA levels has not been clarified. Given that FFAs exert a lipotoxic effect on pancreatic β-cells and might directly damage the arterial endothelium, we hypothesized that these adverse effects might synergize with hyperglycemia. MethodsA total of 9396 Japanese subjects were included in the study. Serum FFA levels were measured at baseline examination. Brachial-to-ankle pulse wave velocity (baPWV) was measured as an index of arterial stiffness. ResultsAs serum levels of FFA were markedly lower in subjects with higher insulin level, a significant association between FFA levels and baPWV was observed only in subjects with blood samples taken under fasting (≥12h, P<0.001) or near-fasting (5–11h, P<0.001) conditions, and not in those taken under non-fasting (<5h, P=0.307) conditions. Although type 2 diabetes and HbA1c showed a strong association with baPWV, the association between FFA level and baPWV remained significant (β=0.052, P<0.001) after adjustment for glycemic levels. In addition to their direct relationship, FFA and glucose levels were synergistically associated with baPWV (FFA⁎glucose; β=0.036, P<0.001). Differences in baPWV between the lowest and highest subgroups divided by a combination of FFA and glucose reached approximately 300cm/s. ConclusionsPhysiological variations in FFA concentrations might be a risk factor for large arterial stiffness. FFA and hyperglycemia exert a synergistic adverse effect on the vasculature.

Nocturnal eating disturbs phosphorus excretion in young subjects: a randomized crossover trial.

BackgroundNocturnal eating have recently increased. Serum phosphorus levels and regulators of phosphorus have circadian variations, so it is suggested that the timing of eating may be important in controlling serum phosphorus levels. However, there have been no reports on the effects of nocturnal eating on phosphorus metabolism.The objective was to evaluate the effects of nocturnal eating on phosphorus metabolism.MethodsFourteen healthy men participated in two experimental protocols with differing dinner times. The design of this study was a crossover study. The subjects were served test meals three times (breakfast; 07:30 h, lunch; 12:30 h, dinner; 17:30 or 22:30 h) a day. Blood and urine samples were collected to assess diurnal variation until the following morning.ResultsThe following morning, fasting serum phosphorus levels in the late dinner group were markedly higher than those in the early dinner group (p < 0.001), although serum calcium levels were maintained at approximately constant levels throughout the day in both groups. Fluctuations in urinary calcium excretion were synchronized with the timing of dinner eating, however, fluctuations in urinary phosphorus excretion were not synchronized. Urinary phosphorus excretions at night were inhibited in the late dinner group. In the late dinner group, intact parathyroid hormone levels didn’t decrease, and they were significantly higher in this group compared with the early dinner group at 20:00 h (p = 0.004). The following morning, fasting serum fibroblast growth factor 23 levels in the late dinner group had not changed, but those in the early dinner group were significantly increased (p = 0.003). Serum free fatty acid levels before dinner were significantly higher in the late dinner group compared with the early dinner group.ConclusionsOur results indicate that nocturnal eating inhibits phosphorus excretion. It is suggested that nocturnal eating should be abstained from to manage serum phosphorus levels to within an adequate range.

Identifying clues to molecular etiology of multiple sclerosis in South Indian patients

BackgroundEnvironmental risk factors have a dominant role in the pathogenesis of multiple sclerosis (MS). Unhealthy lifestyle can predispose people to autoimmune diseases. MS was a rare disease in Kerala, but now, we notice frequent cases of MS at the city neurology clinic. Changing lifestyle and associated changes in the level of proinflammatory biomolecules like: leptin, soluble leptin receptor (SLR) and free fatty acids (FA) could be contributing to rise in MS incidence. ObjectiveTo identify variations in the levels of bio-molecules: leptin, SLR and FA, between MS patients and matched healthy control. Method: Leptin and SLR levels in the blood serum, were estimated using ELISA, while total FA levels, were estimated using an enzyme based calorimetric assay. ResultMean serum FA levels in MS patients (31.39±4.83nmole/100μl) were 2.7 fold higher than controls (11.54±2.66nmoles/100μl) at more than 99% CI. The differences in mean leptin and SLR levels were not statistically significant. ConclusionMS patients had high level of total FA in their blood. High FA in blood may have a role in MS pathogenesis. More in-depth study is required to understand the precise mechanism by which FA rise in MS blood sample can contribute to pathogenesis.

Elevated free fatty acid level is a risk factor for early postoperative hypoxemia after on-pump coronary artery bypass grafting: association with endothelial activation

BackgroundWe aimed to investigate the relationship between increased free fatty acid (FFA) level and early postoperative hypoxemia after coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB).MethodsNinety-eight consecutive patients undergoing CABG were enrolled. Early postoperative hypoxemia was defined as the lowest of the ratio of arterial oxygen tension (PaO2) to inspired oxygen fraction (FiO2) ≤ 200 mm Hg within 24 h without pleural effusion and pneumothorax. The 26 perioperative factors, serum levels of FFA and inflammatory cytokines between the hypoxemia and non-hypoxemia groups were recorded or detected using autoanalyzer and enzyme-linked immunosorbent assay, respectively. Additionally, the risk factors for early postoperative hypoxemia were evaluated using multiple logistic regression analysis.ResultsThe incidence rate of early postoperative hypoxemia was 37.8 %. Serum FFA levels were significantly higher in the hypoxemia group than in the non-hypoxemia group (P < 0.001). Further, postoperative serum FFA levels were inversely related to the lowest of the ratio of PaO2/FiO2 at 24 h after CABG (r = − 0.367, P < 0.001). Multiple logistic regression analysis confirmed that age, body mass index and postoperative serum FFA concentrations were independently associated with early postoperative hypoxemia. Notably, patients with hypoxemia had markedly higher serum intercellular adhesion molecule-1 (ICAM-1) levels than those without (P < 0.001). Moreover, serum FFA levels at 2 h after CABG correlated positively with ICAM-1 concentrations (r = 0.492, P < 0.001).ConclusionsElevated FFA concentration is a risk factor for early postoperative hypoxemia after on-pump CABG, which may be closely associated with endothelial activation.

PPARα/γ agonists and antagonists differently affect hepatic lipid metabolism, oxidative stress and inflammatory cytokine production in steatohepatitic rats

Peroxisome proliferator-activated receptor (PPAR) α/γ may control lipid metabolism and inflammatory response by regulating the downstream target genes, and play a crucial role in the process of non-alcoholic steatohepatitis (NASH) formation, but the difference and interaction between PPARα and PPARγ are poorly understood. The rat model with NASH was established by orally feeding high-fat and high-sucrose emulsion for 6weeks. The results shown that after the model rats were simultaneously treated with PPARα/γ agonists, the total cholesterol (TC), triglyceride (TG) and inflammatory cytokine levels in serum and hepatic tissue, the hepatic steatosis and inflammatory cellular infiltration were decreased, and were consistent with the results of hepatic lipogenic gene and nuclear factor (NF)-κB protein expressions. Conversely, these indexes were increased by PPARα/γ antagonist treatment. Compared with the model group, the serum free fatty acid (FFA) level was increased in the PPARα agonist-treated group, decreased in the PPARγ agonist-treated group, and unchanged in the PPARα/γ agonists-treated group. The hepatic FFA level was low in the PPARα/γ agonists-treated groups, but no significant variation in the PPARα/γ antagonists-treated groups. The increments of hepatic reduced glutathione (GSH) and superoxide dismutase (SOD) contents in the PPARα/γ agonists-treated groups were accompanied by decreased hepatic malondialdehyde (MDA) content. These findings demonstrated that PPARα/γ activation might decrease the hepatic lipid accumulation, oxidative stress and inflammatory cytokine production, and PPARγ could counterbalance the adverse effect of PPARα on circulating FFA. It was concluded that the integrative application of PPARα and PPARγ agonists might exert a synergic inhibitory effect on NASH formation through the modulation of PPARα/γ-mediated lipogenic and inflammatory gene expressions.

베타-글루칸의 고지방 식이 유도 비만쥐에서 체지방 및 혈청지질 개선효과

본 연구는 미생물 유래 베타-글루칸의 항비만 효과를 검증하기 위하여 동물실험을 통해 식이 베타-글루칸이 체지방 형성과 혈중 지질에 미치는 영향을 조사하였다. Sprague-Dawley종 흰쥐를 6주간 고지방 식이로 사육하여 비만을 유도한 후 베타-글루칸을 각각 식이 무게의 0%(고지방 대조군), 0.1%, 0.5%로 함유한 식이로 5주간 사육하였다. 정상 대조군은 AIN-76A 식이로 사육하였다. 고지방식이군에서 단위체중당 체지방이 많았으며, 0.1% 베타-글루칸 공급은 고지방 식이에 의해 유도된 복막지방, 내장지방 축적을 각각 16%와 19% 억제하였고, 혈중 렙틴을 28% 감소시켰다(P 【This study was aimed to investigate the effect of dietary ${\beta}$ -glucan obtained from bacterial fermentation on the adiposity and serum lipids level in rats. Sprague-Dawley rats fed high fat diet for 6 weeks to induce obesity, and subsequently fed with 0% (high fat control group), 0.1% or 0.5% ${\beta}$ -glucan supplemented high-fat diets (w/w) for another 5 weeks. For comparison, normal control groups fed AIN-76A diet. Supplemented with 0.1% ${\beta}$ -glucan resulted in a significant reduction of high-fat induced peritoneal fat and visceral fat development by 16%, 19%, and 28%, respectively(P ${\beta}$ -glucan(P ${\beta}$ -glucan reduced adiposity and improved serum lipids in obese rats fed high fat diet. The present study suggest that ${\beta}$ -glucan supplementation to the diet is beneficial in suppressing diet-induced obesity and dyslipidemia.】

Apelin Enhances Brown Adipogenesis and Browning of White Adipocytes

Brown adipose tissue expends energy in the form of heat via the mitochondrial uncoupling protein UCP1. Recent studies showed that brown adipose tissue is present in adult humans and may be exploited for its anti-obesity and anti-diabetes actions. Apelin is an adipocyte-derived hormone that plays important roles in energy metabolism. Here, we report that apelin-APJ signaling promotes brown adipocyte differentiation by increasing the expressions of brown adipogenic and thermogenic transcriptional factors via the PI3K/Akt and AMPK signaling pathways. It is also found that apelin relieves the TNFα inhibition on brown adipogenesis. In addition, apelin increases the basal activity of brown adipocytes, as evidenced by the increased PGC1α and UCP1 expressions, mitochondrial biogenesis, and oxygen consumption. Finally, we provide both in vitro and in vivo evidence that apelin is able to increase the brown-like characteristics in white adipocytes. This study, for the first time, reveals the brown adipogenic and browning effects of apelin and suggests a potential therapeutic route to combat obesity and related metabolic disorders.

Effects of Biotin Supplementation in the Diet on Adipose Tissue cGMP Concentrations, AMPK Activation, Lipolysis, and Serum-Free Fatty Acid Levels.

Several studies have shown that pharmacological concentrations of biotin decrease hyperlipidemia. The molecular mechanisms by which pharmacological concentrations of biotin modify lipid metabolism are largely unknown. Adipose tissue plays a central role in lipid homeostasis. In the present study, we analyzed the effects of biotin supplementation in adipose tissue on signaling pathways and critical proteins that regulate lipid metabolism, as well as on lipolysis. In addition, we assessed serum fatty acid concentrations. Male BALB/cAnN Hsd mice were fed a control or a biotin-supplemented diet (control: 1.76 mg biotin/kg; supplemented: 97.7 mg biotin/kg diet) over 8 weeks postweaning. Compared with the control group, biotin-supplemented mice showed an increase in the levels of adipose guanosine 3',5'-cyclic monophosphate (cGMP) (control: 30.3±3.27 pmol/g wet tissue; supplemented: 49.5±3.44 pmol/g wet tissue) and of phosphorylated forms of adenosine 5'-monophosphate-activated protein kinase (AMPK; 65.2%±1.06%), acetyl-coenzyme A (CoA), carboxylase-1 (196%±68%), and acetyl-CoA carboxylase-2 (78.1%±18%). Serum fatty acid concentrations were decreased (control: 1.12±0.04 mM; supplemented: 0.91±0.03 mM), and no change in lipolysis was found (control: 0.29±0.05 μmol/mL; supplemented: 0.33±0.08 μmol/mL). In conclusion, 8 weeks of dietary biotin supplementation increased adipose tissue cGMP content and protein expression of the active form of AMPK and of the inactive forms of acetyl-CoA carboxylase-1 and acetyl-CoA carboxylase-2. Serum fatty acid levels fell, and no change in lipolysis was observed. These findings provide insight into the effects of biotin supplementation on adipose tissue and support its use in the treatment of dyslipidemia.

Effect of NAD on PARP-mediated insulin sensitivity in oleic acid treated hepatocytes.

High serum free fatty acids levels are associated with the development of insulin resistance in type 2 diabetes; however, the precise mechanisms underlying this lipid toxicity are unclear. To investigate whether PARP1 activation and NAD depletion are involved in the impairment of insulin sensitivity associated with lipotoxicity, HepG2 cells were cultured with 500 μM oleic acid for 48 h. Oleic acid-treated cells exhibited increased ROS generation, lipid accumulation and PARP1 activation. Treatment with the PARP1 inhibitor PJ34 and transfection with PARP1 small interfering RNA both prevented the oleic acid-induced impairment of the insulin signaling pathway. Furthermore, treatment with PJ34 reversed the oleic acid-induced decrease in intracellular NAD concentration, while exogenous NAD protected cells against oleic acid-induced insulin insensitivity. Combined NAD and PJ34 administration did not enhance the effects obtained by treatment with either NAD or PJ34 alone. Interestingly, when cells were treated with the SIRT1 inhibitor EX527, the protective effects of PJ34 and NAD treatment were diminished. Taken together, these data suggest that NAD depletion by PARP1 activation is essential for the modulation of insulin sensitivity in oleic acid-induced lipotoxicity.

The changes of LCHAD in preeclampsia with different clinical features and the correlation with NADPH P47-phox, p38MAPK-α, COX-2 and serum FFA and TG

Objective To investigate the changes of fatty acid oxidase in the placenta of preeclampsia cases with different clinical features, and the relationship with oxidative stress and inflammatory response. To study the correlation of serum free fatty acid (FFA) and triglycerides (TG) level in early second trimester with the molecular changes of the long-chain fatty acid oxidase in the third trimester. Methods This was prospective cohort study, in which cases with singleton pregnancies who archived in Haidian Maternal and Children's Hospital, Beijing, from January 1st 2012 to May 31st, with regular prenatal care were included. Doppler ultrasound was used for screening for the presence of early diastolic notch of uterine artery at 22-24 weeks of gestation. All the 101 cases with the early diastolic notch of uterine artery were included as the notch group, and 377 cases without the early diastolic notch of uterine artery were included as the non-notch group. The perinatal outcomes and the incidence of hypertensive disorders in pregnancy of the two groups were observed. The serum level of FFA and TG was tested, and the mRNA and protein expression of long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD), P47-phox subunit of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, p38 mitogen-activated protein kinase α(p38MAPK-α) and cyclooxygenase-2 (COX-2) were detected using real-time quantitative PCR and western blot. The relationship between serum level of FFA and TG and the mRNA and protein expression of LCHAD, NADPH P47-phox,p38MAPK-α and COX-2 of the placental tissue specimens were analyzed. Results (1) In the notch group, there were 9 cases of early-onset preeclampsia, 15 cases of late-onset preeclampsia and 10 cases of gestational hypertension; and there were 8 cases of late-onset preeclampsia and 18 cases of gestational hypertension in the non-notch group. 15 cases with normal blood pressure in each group were randomly selected as the control group.(2)The serum level of TG of cases of early-onset preeclampsia, late-onset preeclampsia and gestational hypertension in the notch group were(2.0 ± 0.8),(1.8 ± 0.6) and(1.9±0.7)mmol/L, and that of FFA were(0.68±0.26), (0.52±0.10) and (0.52±0.17) mmol/L, respectively. The serum level of TG of cases of late-onset preeclampsia and gestational hypertension in the non-notch group were(1.6±0.6) and (1.4±0.4) mmol/L, and that of FFA were (0.49±0.11) and (0.48±0.05) mmol/L, respectively. The serum level of TG and FFA in the control group were (1.4±0.5) and (0.52±0.06) mmol/L, respectively. The TG level of the notch group was higher than that of the control group, and the difference was statistically significant (P 0.05) . (6) The mRNA expression of placental LCHAD in the early-onset preeclampsia in the notch group was significantly negatively correlated with the mRNA expression of placental NADPH P47-phox and COX-2 (r=- 0.877,-0.762,P<0.05). The mRNA expression of placental LCHAD in the control group was significantly negatively correlated with the mRNA expression of placental COX-2 (r=-0.565,P<0.01). The protein expression of placental LCHAD in the early-onset preeclampsia in the notch group was significantly negatively correlated with the protein expression of NADPH P47-phox (r=-0.818,P<0.01). The protein expression of placental LCHAD in the control group was significantly negatively correlated with the protein expression of COX-2 (r=-0.502,P<0.01). Conclusions The placental mRNA and protein expression of long-chain fatty acid oxidation enzymes were different in different clinical features of preeclampsia, which were reduced more obviously in the early-onset preeclampsia in the notch group than that of the late-onset preeclampsia in the notch group, and were negatively correlated with the elevated serum FFA level, significantly enhanced oxidative stress and inflammatory response, but with no correlation with serum TG level. Key words: Pre-eclampsia; 3-Hydroxyacyl CoA dehydrogenases; NADPH oxidase; Fatty acids, nonesterified; Triglycerides; Oxidative stress

Quercetin ameliorates insulin sensitivity and liver steatosis partly by increasing adiponectin expression in ob/ob mice

The effects of quercetin on non-alcoholic fatty liver disease (NAFLD) in an obese mouse model were investigated. Five-week-old ob/ob mice were fed an AIN-93G diet or a diet containing 0.08% quercetin, whereas ob/+ mice were provided the AIN-93G diet for 10 weeks. Quercetin significantly decreased serum glucose, triglycerides, cholesterol, and free fatty acid (FFA) levels, and homeostasis model assessment for insulin resistance (HOMA-IR) values, compared with the ob/ob control group. Quercetin lowered hepatic total lipids, triglycerides, and cholesterol levels, and the serum alanine transaminase (ALT) activities, compared with the ob/ob control group. Quercetin increased adiponectin protein expression in epididymal adipose tissue and serum adiponectin levels, and decreased serum tumor necrosis factor-α (TNF-α) and monocyte chemotactic protein-1 (MCP-1), compared with the ob/ob control group. These results indicate that quercetin could exert protective effects against development of NAFLD, partly by overexpression of adiponectin and reduction of inflammatory cytokine levels in ob/ob mice.

Serum Unsaturated Free Fatty Acids: A Potential Biomarker Panel for Differentiating Benign Thyroid Diseases from Thyroid Cancer

Background: Serum free fatty acids (FFAs) are correlated with pathological status, and change in serum FFA levels may be associated with thyroid diseases.Materials and Methods: In this study, 664 serum samples from 322 healthy controls, 129 patients with benign thyroid disease (BTD), and 213 patients with thyroid cancer (TC) were collected. Chip-based direct-infusion nanoelectrospray-mass spectrometry was performed to simultaneously quantify six serum FFAs (i.e., C16:1, C18:1, C18:2, C18:3, C20:4, and C22:6.), with the excellent correlation coefficients of > 0.99 and relative standard deviation of <18% for all analysts. The Mann-Whitney U test was used to compare the differences in serum FFA levels between three above-mentioned groups.Results: Significant increase in the levels of C16:1, C18:1, C18:2, C18:3, C20:4, and C22:6 in healthy controls relative to TC patients and BTD patients was observed, and the levels of C16:1, C18:2, C20:4, and C22:6 in BTD patients were significantly decreased relative to TC patients. Receiver operating characteristic (ROC) analysis indicated that a combination of C16:1, C18:2, C20:4, and C22:6 has excellent diagnostic performance to differentiate BTD patients from TC patients, with an area under the ROC curve of 0.857, a sensitivity of 76.8%, and a specificity of 83.7%.Conclusions: Change in serum levels of FFAs is closely correlated with thyroid diseases, and a biomarker panel (C16:1, C18:2, C20:4, and C22:6) should be of benefit to differentiate BTD patients from TC patients.

Assessment of serum cortisol, malondialdehyde and free fatty acid levels in pre- and post-operative stress

The stress responses are the hormonal and metabolic changes which occur following injury or trauma. This is part of the systemic reaction to injury which encompasses a wide range of endocrinological, immunological and haematological effects. The present study was conducted to evaluate the serum cortisol, malondialdehyde (MDA) and free fatty acid (FFA) levels in pre and postoperative surgical patients. For the present study, 25 patients admitted in surgical ward for different surgeries were selected. The serum cortisol is estimated by enzyme-linked immunosorbent assay and serum MDA and FFA was estimated by spectrophotometer. On comparative evaluation, there was highly significant decrease ( P < 0.001) in the serum cortisol, MDA and FFA levels in the postoperative surgical patients as compared to their preoperative levels. Therefore, from the present study, it could be suggested that serum cortisol, MDA and FFA are associated with the pre and postoperative stress conditions.

Effects of reduced food intake on the parameters of toxicity evaluation in dogs.

It is crucial to evaluate the variations in the toxicity parameters in experimental animals during the development of new drugs. Reduced food intake has been reported to have an impact on the toxicity parameters in rats; however, there are few reports of such studies in dogs. The aim of this study was to clarify the effects of reduced food intake on the general toxicity parameters and their reversibility in dogs. Male beagle dogs were fed 300 g/day of diet for 12 weeks in the control group, and 150 g/day for the first 8 weeks and 200 g/day for the subsequent 4 weeks in the low feeding group. During the following 4-week recovery period, the amount of feeding was set at 300 g/day. There were no clinical changes in any of the dogs. The low feeding group showed a body weight loss of 9.0%, 16.7% and 14.3% relative to the pre-test values at Week 4, 8 and 12, respectively. The following changes from the pre-test values and/or the control group in the examined parameters were observed in this group: decreased heart rate, prolonged PR interval on the ECG, decreased leukocyte count, and increased serum free fatty acid and γ-glutamyl transpeptidase levels. Significant changes of these parameters were not observed any more during the recovery period. This fact supports biological or physiological reaction to reduced food intake. These results are considered to represent useful information for toxicologists to distinguish between the direct effects of drugs and the changes attributable to reduced food intake.

Association of serum-free fatty acid level with reduced reflection pressure wave magnitude and central blood pressure: the Nagahama study.

Central blood pressure (BP) has been suggested to be a better predictor of cardiovascular disease risk than brachial BP. Given that central BP and arterial waveform are both influenced by insulin resistance, major initiators of insulin resistance, such as serum-free fatty acid (FFA), are suspected of potentially being involved in central hemodynamics. To confirm that insulin signaling is an important modulator of central hemodynamics, we investigated this hypothesis in a large-scale general population. Brachial BP and radial arterial waveform were measured simultaneously in 9393 middle-aged to elderly individuals. The augmentation index was calculated from the radial waveform as the ratio of the height of the late systolic peak to that of the first peak. Central systolic BP was defined as the absolute pressure of the late systolic peak of the waveform. Differences in central and brachial pulse pressure (PP) were considered to represent PP amplification. PP amplification differed significantly among serum FFA level quartiles (Q1, 7.8±5.3; Q2, 8.6±5.0; Q3, 9.3±5.7; Q4, 10.3±6.1 mm Hg; P<0.001), and the maximum difference in combination with diabetes mellitus status was 4.9 mm Hg. Multivariate analysis adjusted for major covariates indicated that higher serum FFA was an independent determinant for higher PP amplification (β=0.145, P<0.001) and lower augmentation index (β=-0.122, P<0.001) and central systolic BP (β=-0.044, P<0.001), whereas the association between FFA and PP amplification significantly decreased (β=0.022, P<0.001) after further adjustment for augmentation index. Serum FFA is an overlooked factor favorably influencing central hemodynamics. A low-magnitude reflection pressure wave might be involved in this paradoxical relationship.

Stratification of risk of death in severe acute alcoholic hepatitis using a panel of adipokines and cytokines.

Dysregulated adipose tissue metabolism has been implicated in the pathogenesis of alcoholic liver disease in murine models. We aimed to characterize serum markers of adipose tissue metabolism and inflammation in patients with severe acute alcoholic hepatitis (AAH) and determine their utility to predict survival in severe AAH. A prospective, case-control study design was used. Seventy-six patients hospitalized with severe AAH and 25 ambulatory patients with alcoholic cirrhosis as controls were included. Serum samples were collected for biochemical analyses. Patients were followed for 180days after enrollment to determine the survival. AAH patients exhibited higher serum glycerol and free fatty acid levels, suggesting enhanced adipose tissue triglyceride hydrolysis. Patients with AAH demonstrated a distinct serum lipidomic profile compared with alcoholic cirrhosis but not in systemic and adipose-specific insulin resistance. AAH patients had higher serum resistin and plasmin activation inhibitor-1 levels, while serum leptin was decreased. Serum levels of the prolipolytic cytokines tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-8, and IL-15 were significantly higher in AAH patients. Only 53% of AAH patients survived 180days after admission, while all cirrhotic patients were alive at the end of the study period. Among patients with severe AAH, white blood cell count, hemoglobin, resistin, IL-6 and TNF-α were associated with 180-day survival, and all 5 markers demonstrated accuracy by area under receiver-operator curve analysis. Serum IL-6 levels ≥38.66pg/ml most precisely identified deaths in severe AAH. Patients with IL-6≥38.66pg/ml had significantly decreased mean survival compared to those with lower levels. AAH patients demonstrate evidence of increased adipose tissue lipolysis and altered serum lipidomic profile compared with alcoholic cirrhosis patients. IL-6 may be a useful biomarker to risk stratify severe AAH patients at the highest risk of mortality.

Fatty acid oxidation changes and the correlation with oxidative stress in different preeclampsia-like mouse models.

BackgroundLong-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) expression is decreased in placenta of some cases of preeclampsia (PE) which may result in free fatty acid (FFA) increased. High FFA level will induce oxidative stress, so abnormal long-chain fatty acid-oxidation may participate in the pathogenesis of PE through oxidative stress pathway.MethodsPE-like groups were ApoC3 transgenic mice with abnormal fatty acid metabolism, classical PE-like models with injection of Nw-nitro-L-arginine-methyl ester (L-NA) or lipopolysaccharide (LPS) and the antiphospholipid syndrome (APS) mouse model with β2GPI injection (ApoC3+NS, ApoC3+L-NA, L-NA, LPS and β2GPI groups). The control group was wild-type mice with normal saline injection. Except for β2GPI mice, the other mice were subdivided into pre-implantation (Pre) and mid-pregnancy (Mid) subgroups by injection time.ResultsAll PE-like groups showed hypertension and proteinuria except ApoC3+NS mice only showed hypertension. Serum FFA levels increased significantly except in LPS group compared to controls (P<0.05). LCHAD mRNA and protein expression in the liver and placenta was significantly higher for ApoC3+NS, ApoC3+L-NA and β2GPI mice and lower for L-NA mice than controls (P<0.05) but did not differ between LPS mice and controls. P47phox mRNA and protein expression in the liver significantly increased in all PE-like groups except LPS group, while P47phox expression in the placenta only significantly increased in L-NA and β2GPI groups.ConclusionsAbnormal long-chain fatty acid-oxidation may play a different role in different PE-like models and in some cases participate in the pathogenesis of PE through oxidative stress pathway.

ClC-3 deficiency protects preadipocytes against apoptosis induced by palmitate in vitro and in type 2 diabetes mice.

Palmitate, a common saturated free fatty acid (FFA), has been demonstrated to induce preadipocyte apoptosis in the absence of adipogenic stimuli, suggesting that preadipocytes may be prone to apoptosis under adipogenic insufficient conditions, like type 2 diabetes mellitus (T2DM). ClC-3, encoding Cl(-) channel or Cl(-)/H(+) antiporter, is critical for cell fate choices of proliferation versus apoptosis under diseased conditions. However, it is unknown whether ClC-3 is related with preadipocyte apoptosis induced by palmitate or T2DM. Palmitate, but not oleate, induced apoptosis and increase in ClC-3 protein expression and endoplasmic reticulum (ER) stress in 3T3-L1 preadipocyte. ClC-3 specific siRNA attenuated palmitate-induced apoptosis and increased protein levels of Grp78, ATF4, CHOP and phosphorylation of JNK1/2, whereas had no effects on increased phospho-PERK and phospho-eIF2α protein expression. Moreover, the enhanced apoptosis was shown in preadipocytes from high-sucrose/fat, low-dose STZ induced T2DM mouse model with hyperglycemia, hyperlipidemia (elevated serum TG and FFA levels) and insulin resistance. ClC-3 knockout significantly attenuated preadipocyte apoptosis and the above metabolic disorders in T2DM mice. These data demonstrated that ClC-3 deficiency prevent preadipocytes against palmitate-induced apoptosis via suppressing ER stress, and also suggested that ClC-3 may play a role in regulating cellular apoptosis and disorders of glucose and lipid metabolism during T2DM.

Serum Free Fatty Acids Level in Senile Cataract

Purpose: To evaluate and compare the levels of free fatty acids between senile cataract patients and normal controls.Methods: Fifty consecutive patients with newly diagnosed senile cataract and 50 age- and gender-matched controls were evaluated. Subjects/patients were randomized according to selection criteria. The levels of free fatty acids (FFAs) in serum were measured by gas chromatography–mass spectrometry (GC-MS). Sixteen fatty acids from 14:0 to 24:1 were identified. The values were compared between cataract and control groups by parametric independent sample test and Mann-Whitney U tests.Results: A significant decrease was observed in arachidonic acid (C20:4n-6, ARA), cis-4,7,10,13,16,19-docosahexaenoic acid (C22:6n-3, DHA), tetracosanoic acid (C24: 0), cis-7,10,13,16,19-docosapentaenoic acid (C22:5n-6, DPA), total n-3 long-chain polyunsaturated fatty acids (LC-PUFAs), total n-6 LC-PUFAs, total fatty acids, unsaturated fatty acids (USFAs), polyunsaturated fatty acids (PUFAs), and nonessential fatty acid levels in patients with senile cataract in comparison with healthy persons (p < 0.05).Conclusions: The levels of FFA including DPA, tetracosanoic acid, ARA, and DHA were significantly lower in the senile cataract group compared to that in the normal controls. FFA may be helpful in preventing senile cataract.

Association between serum free fatty acid levels and nonalcoholic fatty liver disease: a cross-sectional study.

High serum free fatty acid (FFA) levels are associated with metabolic syndrome (MS). This study aimed to assess the association of fasting serum FFAs with nonalcoholic fatty liver disease (NAFLD) in a Chinese population. A total of 840 subjects fulfilled the diagnostic criteria of NAFLD and 331 healthy control participants were enrolled in this cross-sectional study. Fasting serum FFA levels and other clinical and laboratory parameters were measured. NAFLD patients had significantly higher serum FFA levels than controls (P < 0.001). Serum FFA levels were significantly and positively correlated with parameters of MS, inflammation indexes, and markers of hepatocellular damage. Elevated serum FFA levels were found in NAFLD subjects with individual components of MS (obesity, hypertriglyceridaemia, and hyperglycaemia). Stepwise regression showed that serum FFA levels were an independent factor predicting advanced fibrosis (FIB-4 ≥ 1.3) in NAFLD patients. Serum FFA levels correlated with NAFLD and could be used as an indicator for predicting advanced fibrosis in NAFLD patients.