Increased Serum Triglyceride Levels Research Articles

Effects of the Fungicide Prothioconazole on Lipid Metabolism in Mice: Whitening Alterations of Brown Adipose Tissue.

With considerable concerns about the associations between metabolic disorders and agricultural biocides, there are scattered data suggesting that the triazole fungicide prothioconazole (PTC) at lower doses than the no observed adverse effect level of 5000 μg/kg/d possibly has the potential to disrupt glycolipid metabolism in mammals. Here, we investigated the effects of 50, 500, and 5000 μg/kg/d of PTC on glycolipid metabolism in mice following 8 weeks of administration via drinking water, with specific attention on brown adipose tissue (BAT) and white adipose tissue (WAT) in addition to the liver. We found that along with the increased serum triglyceride level in the 5000 μg/kg/d group, small fatty vacuoles occurred in livers in all treatment groups, indicating lipid accumulation. No change in WAT was observed, but PTC caused BAT whitening, characterized by adipocyte hypertrophy, more unilocular adipocytes with enlarged lipid droplets, reduced UCP1 levels, and down-regulated Doi2 expression, and even the dose of 50 μg/kg/d was effective. Transcriptomic analysis revealed immune inhibition and circadian rhythm disturbance in BAT from the 5000 μg/kg/d group, which are in agreement with BAT whitening and inactivation. On employing the C3H10T1/2 cells in vitro, we found that PTC treatment concentration-dependently promoted lipid accumulation in brown adipocytes, along with altered expression of thermogenesis-related and circadian genes. Taken together, our study shows that low doses of PTC caused BAT whitening, calling for much attention to the new target by pollutants.

Revealing the effect of sea buckthorn oil, fish oil and structured lipid on intestinal microbiota, colonic short chain fatty acid composition and serum lipid profiles in vivo

In this study, the effects of sea buckthorn oil (SBO), fish oil (FO) and an enzymatically synthesized structured lipid (SL) on serum, short-chain fatty acids (SCFAs) and intestinal microbiota in Sprague–Dawley (SD) rats were investigated. The results demonstrated that FO, SBO, and SL effectively reduced the levels of high-density lipoprotein cholesterol and low-density lipoprotein cholesterol in the serum of SD rats. SBO increased serum triglyceride levels, while FO elevated total cholesterol levels. Furthermore, all three dietary lipids decreased short-chain fatty acid production and enhanced intestinal microbiota diversity. FO increased the abundance of intestinal microbiota including Romboutsia, Lactobacillus, Escherichia-Shigella, and Lachnospiraceae_NK4A136_group. Conversely, all three dietary lipids reduced the abundance of Klebsiella and Blautia. These findings provide a foundation for understanding the functionality of SBO and FO as well as their potential application in synthesizing novel SLs to regulate intestinal microbiota.Graphical

Non-nitrogen-containing bisphosphonates and nitrogen-containing bisphosphonates for the treatment of atherosclerosis and vascular calcification: A meta-analysis.

The role of non-nitrogen-containing bisphosphonates (non-N-BPs) and nitrogen-containing bisphosphonates (N-BPs) in the treatment of atherosclerosis (AS) and vascular calcification (VC) is uncertain. This meta-analysis was conducted to evaluate the efficacy of non-N-BPs and N-BPs in the treatment of AS and VC. The PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang databases were searched from their inception to July 5th, 2023. Eligible studies comparing bisphosphonates (BPs) versus no BPs in the treatment of AS and VC were included. The data were analyzed using Review Manager Version 5.3. Seventeen studies were included in this meta-analysis. Twelve were randomized control trials (RCTs), and 5 were nonrandomized studies. Overall, 813 patients were included in the BPs group, and 821 patients were included in the no BPs group. Compared with no BP treatment, non-N-BP or N-BP treatment did not affect serum calcium (P > .05), phosphorus (P > .05) or parathyroid hormone (PTH) levels (P > .05). Regarding the effect on serum lipids, non-N-BPs decreased the serum total cholesterol (TC) level (P < .05) and increased the serum triglyceride (TG) level (P < .01) but did not affect the serum low-density lipoprotein cholesterol (LDL-C) level (P > .05). N-BPs did not affect serum TC (P > .05), TG (P > .05) or LDL-C levels (P > .05). Regarding the effect on AS, non-N-BPs did not have a beneficial effect (P > .05). N-BPs had a beneficial effect on AS, including reducing the intima-media thickness (IMT) (P < .05) and plaque area (P < .01). For the effect on VC, non-N-BPs had a beneficial effect (P < .01), but N-BPs did not have a beneficial effect (P > .05). Non-N-BPs and N-BPs did not affect serum calcium, phosphorus or PTH levels. Non-N-BPs decreased serum TC levels and increased serum TG levels. N-BPs did not affect serum lipid levels. Non-N-BPs had a beneficial effect on VC, and N-BPs had a beneficial effect on AS.

Implications of Incorporating Plasma Lipoprotein Binding into a Physiologically-Based Pharmacokinetic Model: A Simulation Study with Amiodarone.

Although various lipophilic drugs are bound to lipoproteins, lipoprotein binding in plasma is not usually considered in current physiologically-based pharmacokinetic (PBPK) models. Amiodarone is extensively bound to serum triglyceride-rich lipoproteins. Total plasma amiodarone concentration, which is the sum of both unbound and bound concentrations, increases with increasing serum triglyceride levels. We investigated the impact of lipoprotein binding on amiodarone pharmacokinetics using PBPK modeling and simulations. An amiodarone PBPK model that incorporates plasma lipoprotein binding (LPP model) was developed based on the correlation between serum triglyceride levels and lipoprotein-bound amiodarone. The predicted unbound fraction of amiodarone in plasma and systemic clearance in the LPP and base models (with albumin binding only) were similar, but the coefficients of variation for the LPP model were greater than those for the base model and were closer to the observed data. The total plasma amiodarone concentration predicted using the LPP model increased with higher levels of plasma lipoprotein binding and serum albumin. In contrast, changes in plasma lipoprotein binding and serum albumin levels did not influence the predicted unbound plasma amiodarone concentration at steady-state. This study demonstrates that incorporating plasma lipoprotein binding into a PBPK model improves the accuracy of predicting interindividual variabilities in amiodarone clearance by more reliably predicting the interindividual variability in the plasma unbound fraction of amiodarone. Plasma lipoprotein binding should be considered in PBPK modeling and simulations for lipoprotein-associated drugs if there is available information on the relationship between plasma lipoprotein binding and hyperlipidemia.

Glomerular lipidosis as a feature of renal-limited macrophage activation syndrome in a transplanted kidney: a case report

BackgroundGlomerular lipidosis is a rare histological feature presenting the extensive glomerular accumulation of lipids with or without histiocytic infiltration, which develops under various conditions. Among its various etiologies, macrophage activation syndrome (MAS) is a condition reported to be associated with histiocytic glomerular lipidosis. Here we describe the first case of glomerular lipidosis observed in a renal allograft that histologically mimicked histiocytic glomerulopathy owing to MAS.Case presentationA 42-year-old man underwent successful living-donor kidney transplantation. However, middle-grade proteinuria and increased serum triglyceride levels indicative of type V hyperlipidemia developed rapidly thereafter. An allograft biopsy performed 6 months after the transplantation showed extensive glomerular infiltration of CD68+ foam cells (histiocytes) intermingled with many CD3+ T-cells (predominantly CD8+ cells). Furthermore, frequent contact between glomerular T-cells and histiocytes, and the existence of activated CD8+ cells (CD8+, HLA-DR+ cells) were observed by double immunostaining. There was no clinicopathological data suggesting lipoprotein glomerulopathy or lecithin cholesterol acyltransferase deficiency, both of which are well-known causes of glomerular lipidosis. The histological findings were relatively similar to those of histiocytic glomerulopathy caused by MAS. As systemic manifestations of MAS, such as fever, pancytopenia, coagulation abnormalities, hyperferritinemia, increased liver enzyme levels, hepatosplenomegaly, and lymphadenopathy were minimal, this patient was clinicopathologically diagnosed as having renal-limited MAS. Although optimal treatment strategies for MAS in kidney transplant patients remains unclear, we strengthened lipid-lowering therapy using pemafibrate, without modifying the amount of immunosuppressants. Serum triglyceride levels were normalized with this treatment; however, the patient’s extensive proteinuria and renal dysfunction did not improve. Biopsy analysis at 1 year after the transplantation demonstrated the disappearance of glomerular foamy changes, but the number of glomerular infiltrating cells remained similar.ConclusionTo our knowledge, this is the first reported case of glomerular lipidosis in a transplanted kidney. Increased interaction-activation of histiocytes (macrophages) and CD8+ T-cells, the key pathogenic feature of MAS, was observed in the glomeruli of this patient, who did not demonstrate overt systemic manifestations, suggesting a pathological condition of renal-limited MAS. The clinical effects of triglyceride-lowering therapy were limited, suggesting that hypertriglyceridemia was not the cause of but rather may be a consequence of renal-limited MAS.

Sex differences in FASN protein concentrations in urinary exosomes related to serum triglycerides levels in healthy adults

BackgroundDysregulation of lipid metabolism is the most prominent metabolic alteration observed in obesity, cancer, and cardiovascular diseases. The present study aimed to explore the sex differences associated with lipid metabolism in urinary exosome proteins, and evaluate the correlation of urinary exosome proteins with serum lipid biomarkers.MethodsThe key enzymes regulating lipid metabolism in healthy adults were screened using urinary exosome data. Urinary exosomes were isolated from 120 healthy subjects and the expression of urinary proteins was assessed by Western blotting and ELISA. The correlation between urinary protein concentrations and the levels of serum lipid biomarkers was analyzed using correlation analysis.ResultsThree urinary exosome proteins, namely fatty acid synthase (FASN), phosphoenolpyruvate carboxykinase (PCK1), and ATP-citrate synthase (ACLY) were identified, and only FASN showed sex differences. Sex differences were also observed in the serum triglyceride (TG) levels. Healthy males had higher FASN levels than females, and a moderate positive correlation was found between FASN concentrations and serum TG levels in healthy males (r = 0.479, P < 0.05). FASN concentrations in different age groups were positively correlated with the level of serum TG (18 ~ 30 years, r = 0.502; 31 ~ 44 years, r = 0.587; 45 ~ 59 years, r = 0.654; all P < 0.05). In addition, FASN concentrations was positively related to the increase in serum TG levels (range:1.0 ~ 1.7 mmol/L; r = 0.574, P < 0.05).ConclusionsSex differences were observed in urinary exosome FASN protein levels in healthy adults. FASN protein levels positively correlated with increased serum TG levels. FASN may serve as a novel biomarker to evaluate fatty acid synthesis in the human body.

Indigestible Dextrin Alleviates the Intestinal Absorption of Alpha-linolenic Acid More Markedly Than That of Linoleic Acid in Obese Mice

Linoleic acid (LA) and alpha-linolenic acid (ALA) constitute the main dietary polyunsaturated fatty acids. Indigestible dextrin (DEX) is a dietary fiber that causes a beneficial decrease in lifestyle-related disease risk factors. We investigated the effects of DEX on intestinal absorption of LA and ALA in obese mice. KK-Ay/TaJcl obese mice were fed an ALA- or LA-abundant diet and provided with water in the absence and presence of 0.06 w/v% DEX for 4 weeks. The levels of lipids in serum samples and the lipase activity in serum and liver were analyzed. The effects of DEX on the intestinal absorption of LA and ALA were investigated using an in vitro model of the intestinal absorption process in the fed-state simulated intestinal fluid (FeSSIF) solution. ALA resulted in an increase in the serum triglyceride (TG) levels than those observed upon feeding an LA-abundant diet. DEX suppressed significantly the ALA-dependent increase in serum TG levels. Neither LA nor ALA affected the serum levels of total cholesterol and high-density lipoprotein cholesterol, as well as the serum and hepatic lipase activities. Moreover, ALA showed better solubility than LA in FeSSIF solution. The solubility of ALA in FeSSIF solution was significantly suppressed by DEX, whereas that of LA was not affected by DEX. ALA can be absorbed more easily than LA during the intestinal absorption process, probably leading to an increase in the serum TG levels and then DEX more selectively inhibits the intestinal absorption of ALA compared to that of LA.

Application of serum Raman spectroscopy in rapid and early discrimination of aplastic anemia and myelodysplastic syndrome

BackgroundRaman spectroscopy of hematological diseases has gained attention from various researchers. However, serum analysis of bone marrow failure (BMF), represented by aplastic anemia (AA) and myelodysplastic syndromes (MDS) has not been fully investigated. In this study, we aimed at establishing a simple, non-invasive serum detection method for AA and MDS. MethodSerum samples from 35 AA patients (N = 35), MDS patients (N = 25), and control volunteers (N = 23) were systematically analyzed via laser Raman spectroscopy, and orthogonal partial least squares discrimination analysis (OPLS-DA). Then, discrimination models between the BMFs and control were constructed and evaluated using the prediction set. ResultsCompared to control volunteers, serum spectral data for BMF patients were specific. The intensities of Raman peaks representing nucleic acids (726, 781, 786, 1078, 1190, 1415 cm−1), proteins (1221 cm−1), phospholipid/cholesterol (1285 cm−1), and β-carotene (1162 cm−1) significantly decreased, while the intensity of lipids (1437 and 1446 cm−1) significantly increased. Intensities of Raman peaks representing nucleic acids (726 cm−1) and collagen (1344 cm−1) in the AA group were significantly lower than in the control group. Intensities of Raman peaks representing nucleic acids (726 and 786 cm−1), proteins (1003 cm−1), and collagen (1344 cm−1) in the MDS group were significantly lower than those of the control group. The intensity of Raman peaks representing lipids (1437 and 1443 cm−1) in the MDS group was significantly higher than in the control group. Patients with AA and MDS exhibited increased serum triglyceride levels and decreased high-density lipoprotein levels. ConclusionsThe relationship between serological test data for patients and typing of AA and MDS provides essential information for rapid and early identification of BMF. This study shows the potential of Raman spectroscopy for non-invasive detection of different BMF types.

Variations in Lipid Profile During Critical Illness

Objective: To determine to mean change in levels of Triglycerides (TG), Total cholesterol (TC), High-Density Lipoprotein Cholesterol (HDL-C), and low-density lipoprotein (LDL-C) in critically ill patients at admission,18 hours and 42 hours after admission.&#x0D; Study Design: Cross-sectional study&#x0D; Place and Duration of Study: Department of Chemical Pathology &amp; Endocrinology, Armed Forces Institute of Pathology Rawalpindi (AFIP), in collaboration with Military Hospital Rawalpindi (MH), Combined Military Hospital Rawalpindi (CMH) and Armed Forces Institute of Cardiology Rawalpindi (AFIC) Pakistan, from Mar to Sep 2016.&#x0D; Methodology: A total of Fifty patients admitted to intensive care units of MH, CMH and AFIC for coronary artery disease(CAD), sepsis, burns and cancer were included in the study. Patients on lipid-lowering drugs and post-surgery patients were excluded.TC, HDL-C, LDL-C and TG were analysed on ADVIA 1800 (SIEMENS, Germany).&#x0D; Results: Fifty patients were included with mean age of 48.12±2.26 years. Parametric analyses revealed significant increase in serum TG levels during hospitalization in critically ill patients in various disease groups (Mean±SD at admission, 18 hours and 42 hours): TG (CNS disorders 1.35±0.18, 1.78±0.24 and 1.22±0.17; CVS 1.92±0.21, 2.15±0.28 ,2.32 ±0.20; sepsis 1.55±0.18,1.38+0.24,1.54+0.17; malignancies 1.24±0.31, 1.28+0.42,1.35+0.30; renal disorders 1.39+0.35,1.82+0.47,1.08+0.33; (p&lt;0.05). TC decreased in sepsis, CVS and cancer patients while increasing in CNS and renal disorders. HDL-C and LDL-C decreased in all diseases as an acute stress response.&#x0D; Conclusions: During critical illness, TG and LDL-C may change significantly; therefore, they should be monitored and interpreted with extreme care if requested to be performed within the course of the disease.

A novel nutritional score based on serum triglyceride and protein levels predicts outcomes of intrahepatic cholangiocarcinoma after curative hepatectomy: A multi-center study of 631 patients.

BackgroundHigh serum triglyceride (STG) level is a well-established pathogenic factor for cardiovascular diseases and is associated with the risk of various malignancies. Nevertheless, the role of STG level in intrahepatic cholangiocarcinoma (ICC) remains uncertain.MethodsA total of 631 ICC patients treated with curative hepatectomy in two centers (517 in the discovery set and 114 in the validation set) were retrospectively analyzed. Kaplan–Meier survival analysis was used to assess the outcomes of the patients with different STG levels. Time-dependent receiver operating characteristic (ROC) analysis was conducted to compare the prognostic value of STG with other established indexes. The Triglyceride-Albumin-Globulin (TAG) grade was introduced and evaluated using the time-dependent area under curves (AUC) analysis and decision curve analysis (DCA).ResultsPatients with increased STG levels and decreased albumin-globulin score (AGS) were correlated with improved overall survival (OS) and recurrence-free survival (RFS). STG level ≥ 1 mmol/L was an independent protective factor for surgically treated ICC patients. The predictive value of the TAG grade was superior to the STG or the AGS alone. In decision curve analysis, the net benefits of the TAG grade in the discovery and validation set were higher than STG and AGS.ConclusionThe current study presented strong evidence that ICC patients with higher preoperative STG levels had preferred long-term surgical outcomes. The novel nutritional score based on serum triglyceride, albumin and globulin levels was inextricably linked to the prognosis of the surgically treated ICC patients. Evaluation of the TAG grade before curative hepatectomy may be beneficial for risk stratification and clinical decision support.

Dietary Patterns and Their Association with Metabolic Syndrome and Their Components in Middle-Class Adults from Damascus, Syria: A Cross-Sectional Study.

Prior to the 2016 crisis in Syria, a study conducted in Aleppo found the prevalence of metabolic syndrome to be 39.6%, which is known to be favoured by age and poor lifestyle (including physical inactivity and the consumption of hypercaloric foods, rich in saturated fats, concentrated carbohydrates, and salt), so the objective of this study was to identify the association of different dietary patterns with metabolic syndrome and their components. A cross-sectional analytical study was carried out in 104 adults aged 40 to 65 years who did not suffer from previous diseases. The sample was chosen from middle-class citizens of the city of Damascus who were contacted by telephone; they were explained about the study, the information that would be collected, and the studies that should be carried out in the clinical analysis laboratory of the Private University of Syria. A nutritional and food study was carried out using previously validated forms containing 62 items in which the food intake of the participants was studied. We apply principal component analysis and factor analysis to detect nutritional components and dietary patterns. Dietary pattern 3 (foods with simple carbohydrates and saturated fat) increased glucose levels, while dietary patterns 1 (high intake of calories, protein, and saturated fat) and 5 (fast food) increased serum triglyceride levels. In addition, pattern 1 (carbonated beverages, grains, chicken, and meat) was associated with elevated LDL cholesterol levels and the presence of the metabolic syndrome. The study findings suggest that the presence of metabolic syndrome and its components are associated with dietary patterns high in calories, protein, simple carbohydrates, and saturated fat.

Dietary curcumin supplementation ameliorates placental inflammation in rats with intra-uterine growth retardation by inhibiting the NF-κB signaling pathway

Intra-uterine growth restriction (IUGR) is a serious, commonly occurring reproductive problem in humans. This study aimed to investigate the effects of daily curcumin supplementation during pregnancy on placental inflammation, in a rat model of IUGR. Pregnant rats were divided into three groups based on diet: (1) normal protein (19%) (NP), (2) low protein (8%) (LP), and (3) low protein + 100 mg curcumin/kg bw per day (LPC). The results showed that curcumin accumulation in the serum, placenta and liver. Fetal weight and placental total protein levels were increased in the LPC group compared with those in the LP group. Dietary curcumin supplementation normalized the low protein diet-induced decrease of placental weight, blood sinusoid area, and proliferating cell nuclear antigen (PCNA) protein expression levels. It also reversed the low protein diet-induced increase of serum triglyceride levels and tumor necrosis factor alpha-like (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6) concentrations in both the placenta and serum. Additionally, it normalized the enhanced gene expression levels of the pro-inflammatory cytokines in the LP group to that in the NP group. Furthermore, it downregulated the inhibitor of kappa Balpha (IκBα) and nuclear factor kappa Balpha (NF-κB) phosphorylation. In conclusion, daily curcumin supplementation ameliorates placental inflammation in rats with IUGR by inhibiting the NF-κB signaling pathway.

Effects of Short Term Adiponectin Receptor Agonism on Cardiac Function and Energetics in Diabetic db/db Mice.

ObjectiveImpaired cardiac efficiency is a hallmark of diabetic cardiomyopathy in models of type 2 diabetes. Adiponectin receptor 1 (AdipoR1) deficiency impairs cardiac efficiency in non-diabetic mice, suggesting that hypoadiponectinemia in type 2 diabetes may contribute to impaired cardiac efficiency due to compromised AdipoR1 signaling. Thus, we investigated whether targeting cardiac adiponectin receptors may improve cardiac function and energetics, and attenuate diabetic cardiomyopathy in type 2 diabetic mice.MethodsA non-selective adiponectin receptor agonist, AdipoRon, and vehicle were injected intraperitoneally into Eight-week-old db/db or C57BLKS/J mice for 10 days. Cardiac morphology and function were evaluated by echocardiography and working heart perfusions.ResultsBased on echocardiography, AdipoRon treatment did not alter ejection fraction, left ventricular diameters or left ventricular wall thickness in db/db mice compared to vehicle-treated mice. In isolated working hearts, an impairment in cardiac output and efficiency in db/db mice was not improved by AdipoRon. Mitochondrial respiratory capacity, respiration in the presence of oligomycin, and 4-hydroxynonenal levels were similar among all groups. However, AdipoRon induced a marked shift in the substrate oxidation pattern in db/db mice towards increased reliance on glucose utilization. In parallel, the diabetes-associated increase in serum triglyceride levels in vehicle-treated db/db mice was blunted by AdipoRon treatment, while an increase in myocardial triglycerides in vehicle-treated db/db mice was not altered by AdipoRon treatment.ConclusionAdipoRon treatment shifts myocardial substrate preference towards increased glucose utilization, likely by decreasing fatty acid delivery to the heart, but was not sufficient to improve cardiac output and efficiency in db/db mice.

Fluoropyridmidine use and hypertriglyceridemia among Japanese patients: analysis of adverse event database.

Background The association between fluoropyrimidines except for capecitabine and the risk of hypertriglyceridemia is unclear. Objective To investigate hypertriglyceridemia in patients receiving fluoropyrimidines. Method This observational study used anonymized patient data recorded in the open-access Japanese Adverse Drug Event Report database. All fluoropyrimidine and taxane users were investigated. Results We identified 29,451 fluoropyrimidine users and 21,266 taxane users. Disproportionality for both hypertriglyceridemia and an increase in serum triglyceride levels was observed in fluoropyrimidine users compared with in taxane users (reporting odds ratio, 6.74; 95% confidence interval [CI] 2.05-22.17; P < .001). Multivariate logistic analysis showed that both hypertriglyceridemia and an increase in serum triglyceride levels among fluoropyrimidines users were significantly associated with doxifluridine use (odds ratio [OR] 42.50; 95% CI 5.34-338.00; P < .001), tegafur use (OR 9.56; 95% CI 2.08-43.90; P < .001), capecitabine use (OR 12.30; 95% CI 2.67-56.80; P < .001), and breast cancer (OR 5.61; 95% CI 1.07-29.50; P = .042). Conclusion This study suggests that the use of tegafur and doxifluridine is associated with an increased risk of hypertriglyceridemia similar to that with the use of capecitabine; in particular, fluoropyrimidine users with breast cancer may have a high risk of hypertriglyceridemia.

Lower triglyceride levels are associated with better endothelial function

Increased serum triglyceride levels are independently associated with endothelial dysfunction. However, there is little evidence to define normal levels of triglycerides and there is little information on endothelial function in subjects with extremely low levels of triglycerides. The purpose of this study was to determine the relationship between triglycerides, especially low levels of triglycerides, and vascular function. We measured flow-mediated vasodilation (FMD) in 7047 subjects and nitroglycerine-induced vasodilation (NID) in 1017 subjects. We divided the subjects into eight groups by triglyceride levels: <50 mg/dL, 50-69 mg/dL, 70-89 mg/dL, 90-109 mg/dL, 110-129 mg/dL, 130-149 mg/dL, 150-199 mg/dL, and ≥200 mg/dL. FMD was significantly higher in subjects with triglyceride levels of <50 mg/dL than in subjects with triglyceride levels of 50-69 mg/dL, 70-89 mg/dL, 90-109 mg/dL, 110-129 mg/dL, 130-149 mg/dL, 150-199 mg/dL, and ≥200 mg/dL (p=0.002, p<0.001, p<0.001, p<0.001, p<0.001, p<0.001, and p<0.001, respectively). Using triglyceride levels of >200 mg/dL as a reference, the odds ratios for a lower quartile of FMD were significantly lower in the <50 mg/dL group, 50-69 mg/dL group, 70-89 mg/dL group, and 90-109 mg/dL group after adjustment for age, gender and other cardiovascular risk factors. There was a slight negative correlation between NID and triglycerides (r=-0.074; p=0.019). However, there was no significant differences in NID among the eight groups. FMD values were highest in subjects with extremely low levels of triglycerides (<50 mg/dL). Lower triglyceride levels were associated with better endothelial function. http://www.umin.ac.jp (University Hospital Medical Information Network Clinical Trials Registry) (UMIN000012950).

Beneficial effects of the consumption of sun-dried radishes (Raphanus sativus cv. YR-Hyuga-Risou) on dyslipidemia in apolipoprotein E-deficient mice.

In the present study, we evaluated the effects of daily consumption of raw (RR) or sun-dried (SDR) radishes (Raphanus sativus cv. YR-Hyuga-Risou) on apolipoprotein E-deficient (ApoE-/- ) mice. Daily consumption of RR for 16weeks significantly decreased body weight gain in the both wild-type and ApoE-/- mice. The wild-type mice fed the SDR diet gained significantly less body weight than the ApoE-/- mice fed the same diet, although the ApoE-/- mice showed a trend toward decreased body weight gain. Consumption of both diets led to a marked decrease in visceral fat weight and serum triglyceride levels in ApoE-/- mice. Oral fat tolerance tests indicated that pretreatment with RR or SDR mitigated the increase in serum triglyceride levels seen after oil administration. In conclusion, we found that daily consumption of both RR- and SDR-containing diets can help us to prevent from dyslipidemia by inhibiting fat absorption.

O-1602 Promotes Hepatic Steatosis through GPR55 and PI3 Kinase/Akt/SREBP-1c Signaling in Mice.

Non-alcoholic fatty liver disease is recognized as the leading cause of chronic liver disease. Overnutrition and obesity are associated with hepatic steatosis. G protein-coupled receptor 55 (GPR55) has not been extensively studied in hepatic steatosis, although its endogenous ligands have been implicated in liver disease progression. Therefore, the functions of GPR55 were investigated in Hep3B human hepatoma cells and mice fed high-fat diets. O-1602, the most potent agonist of GPR55, induced lipid accumulation in hepatocytes, which was reversed by treatment with CID16020046, an antagonist of GPR55. O-1602 also induced intracellular calcium rise in Hep3B cells in a GPR55-independent manner. O-1602-induced lipid accumulation was dependent on the PI3 kinase/Akt/SREBP-1c signaling cascade. Furthermore, we found increased levels of lysophosphatidylinositol species of 16:0, 18:0, 18:1, 18:2, 20:1, and 20:2 in the livers of mice fed a high-fat diet for 4 weeks. One-week treatment with CID16020046 suppressed high-fat diet-induced lipid accumulation and O-1602-induced increase of serum triglyceride levels in vivo. Therefore, the present data suggest the pro-steatotic function of GPR55 signaling in hepatocytes and provide a potential therapeutic target for non-alcoholic fatty liver disease.

GCSF deficiency attenuates nonalcoholic fatty liver disease through regulating GCSFR-SOCS3-JAK-STAT3 pathway and immune cells infiltration.

Granulocyte colony stimulating factor (GCSF) is a cytokine with immunomodulation effects. However, little is known about its role in metabolic diseases. In the current study, we aimed to explore the role of GCSF in nonalcoholic fatty liver disease (NAFLD). Male GCSF-/- mice were used to investigate the function of GCSF in vivo after high-fat diet (HFD). Primary hepatocytes were used for evaluating the function of GCSF in vitro. Liver immune cells were isolated and analyzed by flow cytometry. Our results showed that GCSF administration significantly increased serum triglyceride (TG) levels in patients. Circulating GCSF was markedly elevated in HFD-fed mice. GCSF-/- mice exhibited alleviated HFD-induced obesity, insulin resistance, and hepatic steatosis. Extra administration of GCSF significantly aggravated palmitic acid (PA)-induced lipid accumulation in primary hepatocytes. Mechanically, GCSF could bind to granulocyte colony stimulating factor receptor (GCSFR) and regulate suppressors of cytokine signaling 3, Janus kinase, signal transducer and activator of transcription 3 (SOCS3-JAK-STAT3) pathway. GCSF also enhanced hepatic neutrophils and macrophages infiltration, thereby modulating NAFLD. These findings suggest that GCSF plays an important regulatory role in NAFLD and may be a potential therapeutic target for NAFLD.NEW & NOTEWORTHY We found GCSF was involved in lipid metabolism and NAFLD development. GCSF administration increased serum triglyceride levels in patients. GCSF deficiency alleviated HFD-induced insulin resistance and hepatic steatosis in mice. GCSF could directly act on hepatocytes through GCSFR-SOCS3-JAK-STAT3 pathway, and regulate the infiltration of immune cells into the liver to indirectly modulate NAFLD. Our finding indicates that GCSF may provide new strategies for the treatment of NAFLD.

Sedum emarginatum and its polysaccharide have a therapeutic effect on alcoholic liver disease in mice

Objective: To explore the therapeutic effect of Sedum emarginatum (SE) and its polysaccharide on alcoholic liver disease. Methods: First, we ground fresh SE to obtain homogenate, and then test the effect of SE on a mouse model of acute alcoholic fatty liver disease (AFLD). Kunming female mice were given intragastric administration of alcohol once every 12 hours to induce AFLD, three times in total, and the mice received ethanol and SE at the same time. The mice were sacrificed 4 hours after the last alcohol administration, and serum and liver were collected for testing. We found that SE was effective and then carried out subsequent experiments. The dried SE powder was extracted under heating and reflux by different polar solvents: petroleum ether, ethyl acetate, methanol and water. The extracting solution were heat and concentrated to obtain an extract. The water part was purified to obtain polysaccharide. We tested the therapeutic effect of each part of SE in a mouse model of early alcoholic hepatitis (AH). Mice were given 5 g/kg of alcohol every 12 hours, a total of 9 times, and lipopolysaccharide (LPS) was injected intraperitoneally at the 36 h and 84 h. After 4 hours of the last gavage, the mice were sacrificed. The serum and liver tissue were used to tested relevant biochemical indexes. Results: SE had a certain reversal effect on the increase of serum triglycerides caused by alcohol, and it had a better effect on the accumulation of lipid droplets in liver tissues. Oil red O staining proved this result. In the second acute experiment, the mortality rate of the animal in the model group was 7/12, and the mortality rate in each treatment group was 1/8, 1/7, 4/8, and 1/8. In all parts, the crude polysaccharide did not significantly reverse the increase of serum triglyceride levels in early AH, but it could significantly alleviate the increase of inflammatory foci and steatosis in liver tissue. The transmission electron microscopy result indicates that the crude polysaccharide component has a certain protective effect on mitochondrial damage caused by alcohol. Conclusion: SE can reduce fatty liver and hyperlipidemia caused by alcohol, and its polysaccharide can reduce liver inflammation in the early alcoholic hepatitis by protecting mitochondron.

P0879EARLY STEROID WITHDRAWAL HAS A POSITIVE EFFECT ON BONE KIDNEY TRANSPLANT RECIPIENTS: A PROPENSITY SCORE STUDY WITH INVERSE PROBABILITY-OF-TREATMENT WEIGHTING

Abstract Background and Aims Long-term corticosteroid use after kidney transplantation is associated with a decrease in bone mineral density and a high fracture risk. We hypothesized that patients with early steroid withdrawal (ESW) would display a gain in bone mineral density in the year following kidney transplantation, when compared with patients on long-term corticosteroid therapy (LTCT). Method In a cohort of kidney transplant recipients, 317 patients were included between 2012 and 2018. Dual-energy X-ray absorptiometry was performed 1 and 12 months after transplantation. The data were analyzed using linear regression with inverse probability-of-treatment weighting based on a propensity score. Results One year after transplantation, the gain in bone mineral density was significantly greater in recipients with ESW than in recipients on LTCT for the lumbar spine (+0.027 g/cm, P &amp;lt; 0.001) and the femoral neck (+0.021 g/cm, P = 0.035). Among patients with ESW, (i) none had osteoporosis, (ii) the percentage with normal bone mineral density increased from 35.0% at month 1 to 56.4% at month 12, and (ii) the percentage with osteopenia fell from 52.5% to 43.6%. In patients undergoing LTCT, the fracture incidence was 14.5 per 1000 person-years. None of the patients in the ESW group experienced a fracture. Cardiovascular risk factors were more prominent in the LTCT group relative to the ESW group: patients in LTCT group (i) were more likely to have high blood pressure (p&amp;lt;0.001), (ii) gained more weight gain (p=0.032) and (iii) displayed a greater increase in serum triglyceride levels (p=0.004).The acute rejection rate was similar in the two groups. Conclusion Early steroid withdrawal is associated with a spontaneous increase in bone mineral density at 12 months post-transplantation (relative to patients on long-term steroid therapy), with a reduction in several cardiovascular risk factors and does not appear to harm the graft.