Research progress on role of free fatty acid receptors in nervous system diseases / 中国生物制品学杂志

@#Free fatty acid receptors(FFARs)are a series of orphan G protein-coupled receptors(GPCRs)activated by free fatty acids(FFAs)and their derivatives. As transmembrane receptors,GPCRs are involved in the occurrence and development of many diseases and provide a wide range of therapeutic targets for these diseases. FFARs combined with FFAs are mainly involved in the secretion of endocrine hormones such as insulin,adipocyte differentiation,inflammatory response,autoimmune response and other processes,which was a potential therapeutic target for energy metabolism disorders and immune diseases. However,recent studies have shown that FFAs and its receptor FFARs are widely involved in neuroinflammation and neuroimmunity directly or through the brain-intestinal axis,and are expected to be a therapeutic target for multiple sclerosis,Alzheimer′s disease(AD),Parkinson′s disease(PD),depression and other diseases. This paper reviews the research progress of the role of FFARs in nervous system diseases.

Improvement effect and mechanism of different extracts from Tylophora yunnanensis on non-alcoholic steato-hepatitis / 中国药房

OBJECTIVE To investigate the improvement effect and mechanism of different extracts from Tylophora yunnanensis on non-alcoholic steatohepatitis （NASH）. METHODS Normal human liver LO2 cells were induced to steatosis by free fatty acid， then were divided into normal group， model group， silybin group （100 μmol/mL）， T. yunnanensis ethanol extracts （TYS） group （50 μg/mL）， T. yunnanensis ethyl acetate extracts （TYSA） group （50 μg/mL）， and T. yunnanensis n-butanol extracts （TYSB） group （50 μg/mL）. After 24 hours of drug intervention， the deposition of lipid droplets was observed in LO2 cells in each group. The contents of total cholesterol （TC）， triacylglycerol （TG）， malondialdehyde （MDA） and glutathione （GSH）， the activities of aspartate transaminase （AST）， alanine transaminase （ALT） and superoxide dismutase （SOD）， the mRNA expressions of Kelch-like ECH-associated protein 1（ Keap1）， nuclear factor E2-related factor 2（ Nrf2） and heme oxygenase 1（ HO- 1） were detected. NASH rat model was induced by a high-fat diet， and then divided into normal group， model group， silybin group （12.6 mg/kg）， TYS group （80 mg/kg）， TYSA group （80 mg/kg） and TYSB group （80 mg/kg）， with six rats in each group. The liver indexes of rats in each group were calculated after 6 weeks of drug intervention. The liver histopathological changes were observed， and the contents of TC， TG， HDL-C and LDL-C， AST and ALT activities in serum， the contents of MDA and GSH， SOD activities in liver tissue were detected. RESULTS Compared with model group， TYS， TYSA and TYSB could reduce lipid droplet deposition， intracellular TC， TG and MDA contents， AST and ALT activities， and increase SOD activity， GSH content， and Keap1， Nrf2， HO-1 mRNA expression levels in LO2 cells after steatosis to varying degrees， with some differences being statistically significant （P＜0.05）. They also significantly improved liver injury in NASH model rats， reduced their liver indexes， TC， TG， LDL-C and MDA contents， AST and ALT 1-042） activities， and increased HDL-C （except for TYS and TYSB）， GSH contents and SOD activity， with TYSA having the most significant effect （P＜0.05）. CONCLUSIONS TYS， TYSA and TYSB have a certain improvement effect on NASH， among which TYSA has the most obvious effect. Its mechanism of action may be related to upregulating the Keap1/Nrf2/HO-1 signaling pathway and inhibiting oxidative stress

The role of lipids and fatty acid metabolism in the development of prostate cancer

The reprogramming of lipid metabolism and signaling pathways is the central aspect of cancer biology. It is hypothesized that tumor cells can alter the lipid spectrum in order to fulfill their metabolic requirements. Furthermore, they can alter potential tumors and suppressive mechanisms in which lipids' involvement is essential. Recently, more attentions have been given on the alteration of lipid metabolism during prostate cancer development, and investigations have shown unique regulation of "de novo" lipid synthesis in cancer cells. Cancer cells often use newer pathways and enzymes to simplify the synthesis of fatty acids, and the newly synthesized lipids affect cellular processes, which impacts cancer cell proliferation and survival outcomes. Herein, we aimed to study the influence of lipid profile alterations on the development of prostate cancer. We found that the total amounts of lipids and phospholipids were increased within tissues from men with the malignant prostate tumor as compared with the benign prostate tissue. Significant changes were also observed in the composition of saturated and unsaturated fatty acids within the malignant tumor tissues. Intensification of lipid peroxidation has also been observed in malignant prostate tumors compared to benign prostate tumors. Collectively, these findings further highlights the fact that lipid and fatty acids play unique regulatory roles in the cellular development of prostate malignant transformation.

Relación entre el índice de masa corporal y el nivel de los ácidos grasos circulantes maternos como predictores de la presencia de la macrosomía fetal / Relationship between body mass index and maternal circulating fatty acid levels as predictors of the presence of fetal macrosomia

Introducción: los recién nacidos con peso elevado al nacer presentan mayor riesgo de complicaciones en el parto y problemas de salud a largo plazo. Un factor poco explorado durante la gestación es el nivel de los ácidos grasos circulantes. Materiales y métodos: estudio prospectivo donde se estudiaron mujeres durante el embarazo hasta el parto. Se analizaron las variables antropométricas y la medición de ácidos grasos libres entre las semanas 24-28 de gestación. Resultados: se incluyeron 27 pacientes, de las cuales cuatro (13,8%) dieron a luz a recién nacidos macrosómicos. Las pacientes se agruparon según el índice de masa corporal (IMC) preembarazo en normopeso y sobrepeso u obesidad. Los bebés macrosómicos correspondieron al grupo de madres con sobrepeso y obesidad que, además, tuvieron un incremento significativo de los niveles de ácidos grasos libres (2067 uM, ICC: 947,5-1590 vs 1212 uM, ICC: 13367-2247; p<0,05) en el grupo obesidad y sobrepeso. Los valores de glucemia basal y posteriores a la prueba de tolerancia oral a la glucosa no mostraron diferencias. El análisis multivariado reveló que tener obesidad o sobrepeso al inicio del embarazo resulta en un odds ratio (OR) de ácidos grasos libres de 1,0023 (IC9 5%:1,0000-1,0046), mientras que la prueba de tolerancia oral a la glucosa presentó un OR: 1,0186 (IC 95%: 0,9645-1,0756). Conclusiones: los resultados muestran el rol del IMC pregestacional sobre el riesgo de tener hijos macrosómicos, lo que confirma la necesidad de mejorar el estado nutricional de las mujeres antes y durante el embarazo.

Introduction: neonates with high birth weight are at increased risk of birth complications and long term health problems. An unexplored factor during gestation is the level of circulating fatty acids. Materials and methods: prospective study where women were studied during pregnancy until delivery. Anthropometric variables and free fatty acid measurements were analyzed between 24-28 weeks of gestation. Results: we included 27 patients, of whom 4 (13.8%) gave birth to macrosomic newborns. Patients were grouped according to pre-pregnancy mass index (BMI) into normal weight and overweight or obese. Macrosomic neonates corresponded to the group of overweight and obese mothers, who also presented a significant increase in free fatty acid levels (2067 uM, ICC: 947,5-1590 vs 1212 uM, ICC: 13367-2247; p<0.05) was found in the obese and overweight group. Basal and post oral glucose tolerance test showed no differences, Multivariate analysis showed that being obese or overweight at the beginning of pregnancy results in an OR of free fatty acids 1,0023 (95%CI: 1,0000-1,0046), while oral glucose tolerance test presented an OR: 1,0186 (95%CI: 0,9645-1,0756). Conclusions: the results show the role of pre-gestational BMI on the risk of having macrosomic children, confirming the need to improve the nutritional status of women before and during pregnancy

Inverse association of plasma hydrogen sulfide levels with visceral fat area among Chinese young men: a cross-sectional study

ABSTRACT Objective: To investigate the association between plasma Hydrogen Sulfide (H2S) levels and visceral fat area (VFA) among Chinese young men. Subjects and methods: This cross-sectional study involved 156 Chinese male subjects, aged 18-45 years, who visited the First Hospital of Qinhuangdao (Hebei, China) in 2014 for annual health check-up. Participants were categorized into: low (VFA < 75.57 cm2), medium (75.57 cm2 ≤ VFA<100.37 cm2), and high (VFA ≥ 100.37 cm2) (n = 52/group). We estimated VFA and plasma H2S levels by using bioelectrical impedance analysis and a fluorescence probe-based approach, respectively. The associations of H2S with VFA and obesity anthropometric measures were assessed. Results: In the high VFA group, the body mass index (BMI, 30.4 ± 2.45 kg/m2), total body fat (TBF, 27.9 ± 3.23 kg), plasma H2S (3.5 μmol/L), free fatty acid (FFA, 0.6 ± 0.24 mmol/L), triglyceride (TG, 2.0 mmol/L), and total cholesterol (TC, 5.5 ± 1.02 mmol/L) levels were significantly higher than that of those of the low and medium VFA groups, respectively (P < 0.05). Plasma H2S levels were found to be inversely correlated with VFA, TBF, waist circumference, BMI, FFA, LnFINS, LnHOMA-IR, LnTG, TC, and LDL-C (P < 0.05). Multiple backward stepwise regression analysis revealed an inverse correlation of plasma H2S levels with FFA (β = −0.214, P = 0.005) and VFA (β = −0.429, P < 0.001), independent of adiposity measures and other confounding factors. Conclusion: VFA was independently and inversely associated with plasma H2S levels among Chinese young men. Therefore, determining plasma H2S levels could aid in the assessment of abnormal VAT distribution.

La suplementación con zinc reduce la concentración de ácidos grasos libres en pacientes con diabetes tipo 2

RESUMEN Elevadas concentraciones de ácidos grasos libres (AGL) han sido asociadas con la patogénesis de resistencia a la insulina y diabetes tipo 2 (DT2), por lo que la regulación de la lipólisis resulta prioritaria en estos pacientes. El zinc mediante sus acciones insulinomiméticas e inducción de fosfodiesterasas podría regular la liberación de AGL desde el tejido adiposo. El objetivo de esta investigación fue evaluar en pacientes con DT2 el efecto de 24 meses de suplementación con zinc sobre las concentraciones séricas de AGL en ayuno. Para este propósito: se realizó la determinación de AGL en ayuno por colorimetría enzimática, zinc plasmático por espectrofotometría de absorción atómica, y parámetros bioquímicos y antropométricos de interés en 60 pacientes con DT2 que fueron asignados aleatoriamente para recibir suplementación con 30 mg/día de zinc (n= 30) o placebo (n= 30) por 24 meses. El grupo zinc presentó menor concentración sérica de AGL al mes 24 (p = 0,034). El cambio en el índice de masa corporal, el sexo y la suplementación con zinc contribuyeron significativamente como predictores de la concentración sérica de AGL al mes 24 (R= 0,493, R2= 0,243, p= 0,001). Conclusión: la suplementación con 30 mg/día de zinc en pacientes con DT2 tuvo un efecto significativo en reducir la concentración sérica de AGL en ayuno tras 24 meses de tratamiento. Estos resultados apoyan los beneficios del zinc como coadyuvante en el tratamiento de DT2.

ABSTRACT High concentrations of free fatty acids (FFA) have been associated with the pathogenesis of insulin resistance and type 2 diabetes (T2D), making lipolysis regulation a priority in these patients. Through its insulin-mimetic actions and phosphodiesterase induction, zinc could regulate FFA release from adipose tissue. The objective of this research was to evaluate the effect of 24 months of zinc supplementation on fasting serum FFA concentrations in patients with T2D. For this purpose: fasting FFA by enzymatic colorimetric, plasma zinc by atomic absorption spectrophotometry, and biochemical and anthropometric parameter of interest were determined in 60 T2D patients who were randomly assigned to 30 mg/day of zinc supplementation (n= 30) or placebo (n= 30) for 24 months. The zinc group had lower serum FFA concentration at month 24 (p= 0.034). Body mass index change, gender, and zinc supplementation contributed significantly as predictors of serum FFA concentration at month 24 (R= 0.493, R2= 0.243, p= 0.001). Conclusion: Supplementation with 30 mg/day of zinc in patients with T2D had a significant effect in reducing serum fasting FFA concentration after 24 months of treatment. These results support the benefits of zinc as coadjutant in T2D treatment.

The Activity of Cordyline Terminalis’s Leaf Extract as Antidiabetic in Obese Wistar Rats

Introduction: Maintaining a quality of life and also doing regular resistance training are the hallmarks of a fit person. Thepurpose of this study is to examine the effect of resistance training (RT) on the selected physical and physiological variablesamong the university males. Method: This is an experimental research with a pre and post-test design which includes aresistance training and a control group. Sixty male participants were selected for this study who were assigned into twogroups; group-A (N=30) experimental group, and group –B (N=30), control group. The participants’ age was in the rangebetween 18 to 22 years. The duration of the RT program was 45 minutes, twice per week. All the subjects were tested beforeand after the 12-week program. For statistical analysis, ANCOVA and SPSS 16 were used. Descriptive statistics was appliedto observe the differences among the participants from the pre to post-test. Results and Discussion: According to the results,the effect of RT on the selected physical variables was significant i.e. body composition, explosive power, muscular strength,muscular endurance, and flexibility. There was also a significant difference with regard to the physiological variables i.e.resting pulse rate and breadth holding time. Lastly, no significant difference was observed for blood pressure (systolic) and(diastolic) showed changes from the pre to post-test. Conclusion: This is evident that RT is beneficial for the improvement ofphysical as well as physiological variables. The higher number of training sessions in a week will be more effective inimproving overall fitness level among the students.

Association of serum CMPF level with fatty acid metabolism and obesity in community population / 中华内分泌代谢杂志

Objective To detect the serum level of 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF),a significant metabolite offish oil,in subjects with normal glucose tolerance (NGT) in local communities,and to investigate the association of CMPF with fatty acid metabolism.Methods A total of 272 NGT participants from screening for diabetes in Shanghai in 2013 were enrolled.Anthropometric measurements,biochemical evaluation,and questionnaire interview were performed for all the participants.The participants were divided into normal weight group [body mass index (BMI) ≤23.9 kg/m2,n =143] and overweight/obesity group (BMI ≥ 24 kg/m2,n =129).The serum CMPF concentrations were determined using an enzyme-linked immunosorbent assay.Results Serum CMPF level in overweight/obesity group was lower than that in normal weight group [96.50 (46.11,169.56) μmol/L vs 153.20 (83.16,282.97) μmol/L,P＜0.05].The serum CMPF level was negatively correlated with BMI (r =-0.256,P＜0.01),triglycerides (r =-0.175,P =0.004),and free fatty acid (r =-0.126,P =0.041) according to bivariate correlation analyses.A multivariate stepwise linear regression analysis showed that the serum CMPF level was independently associated with BMI,triglycerides,free fatty acid,and HbA1C.A logistic regression analysis showed that the CMPF was a protective factor against obesity (OR =0.324,95％ CI 0.158,0.664).Conclusion Serum CMPF level is reduced in overweight/obese subjects.CMPF is beneficial to lipid metabolism.

Replacing soybean oil with increasing levels of soybean acid oil in diets of coturnix quails (Coturnix coturnix coturnix) and the effects on egg quality

ABSTRACT The effects of increasing levels of soybean acid oil in diets of quails on the quality of eggs were evaluated over a period of 56 days. A completely randomized design with five treatment levels of soybean acid oil (0, 2, 4, 6, and 8%) as a replacer for soybean oil and eight replicates of two quails each were used. A total of 240 fresh eggs were used for quality analysis, and 400 eggs were stored at 23ºC over a period of 0, 7, 14, 21, and 28 days for analysis of shelf-life. Polynomial regression and ANOVA with repeated measurements and Tukey´s tests were used. Soybean acid oil linearly increased the intensity of red (a* = -5.26 + 0.14 x, R2 = 0.89, P = 0.01) and yellow (b* = 42.32 + 0.44 x, R2 = 0.88 P = 0.01). All other variables of egg quality were not affected by the treatments, with the exception of sensory attributes, such as odor and aftertaste, which were more pronounced with soybean acid oil. In conclusion, soybean acid oil affects the intensity of yellow and red color of the yolk. Trained assessors detected differences in odor and aftertaste of eggs when soybean acid oil was included in the quail diet.

lntervention effects of the triterpenoids from Cyclocarya paliurus on free fatty acids-induced steatosis in HepG2 cells / 中国药科大学学报

To investigate the therapeutic effects of triterpenoids from Cyclocarya paliurus on non-alcoholic fatty liver disease (NAFLD),the model of NAFLD in HepG2 cells was induced by free fatty acids (FFAs). Cytotoxicity of the triterpenoids from C. paliurus was determined by MTT method,and the effects of triterpenoids without cytotoxicity on intracellular triglyceride (TG)and superoxide dismutase (SOD)were detected by the kits. Data indicated that compound 4 [2α,3α,23-trihydroxy-12,20 (30)-dien-28-ursolic acid,TUA]had hypolipidemic and antioxidant activities. After being treated with TUA and FFAs for 24 h,the intracellular lipid content was observed using Oil Red O staining,and intracellular TG,malondialdehyde (MDA ),SOD and reactive oxygen species (ROS)levels were determined by the assay kits. The protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2),heme oxygenase-1 (HO-1 )and NAD (P)H quinone oxidoreductase 1 (NQO-1 )were measured by Western blot. The results showed that TUA significantly increased SOD activity,and decreased intracellular TG, ROS and MDA levels in FFAs-induced HepG2 cells. Moreover,TUA dramatically improved Nrf2,NQO-1 ,and HO-1 expression. However,the dramatic increase in TG,ROS,MDA levels and the reduction in SOD,NQO-1 and HO-1 expression following Nrf2 inhibitor brusatol treatment were observed. In conclusion,these results suggest that TUA has the therapeutic effect on NAFLD which may be associated with Nrf2 activation.

Effect of dehydroepiandrosterone on fatty acid metabolism in the liver of high-fat diet-induced obese rats / 中华内分泌代谢杂志

Objective To explore the role of dehydroepiandrosterone ( DHEA) in fatty acid metabolism in the liver of obese rats induced by high fat diet. Methods Twenty-seven SD rats were divided into control group, high-fat diet group ( HF group ) , and high-fat diet combined with DHEA treatment group ( DHEA group ) . The serum glucose and insulin levels were determined, while the free fatty acids ( FFA ) level was measured by liquid chromatography-tandem mass spectrometry (LC-MS). The mRNA expressions of hormone-sensitive lipase (HSL), lipoprotein lipase ( LPL ) , acetyl-CoA carboxylase ( ACC ) , fatty acid synthase ( FAS ) , carnitine acyl-CoA transferase (CPT), and stearoyl-CoA desaturase 1 ( SCD1) were measured by real-time PCR. Finally, oil red O staining was also used to observe the changes in hepatic lipid deposition. Results ( 1) The content of hepatic FFA in HF group was significantly higher than that in control group ( P<0.05) , but decreased in DHEA group compared with that in HF group (P<0.05). (2) Compared with HF group, the mRNA expressions of HSL, LPL, ACC, FAS in DHEA group were significantly lower while the mRNA expressions of CPT1, CPT2, and SCD1 were significantly higher ( all P<0.05). (3) Oil-red O staining showed that the liver lipid content in high fat diet-fed rats were significantly increased compared with that in the chow diet group( P<0.05) , but there was no difference between HF and DHEA groups. However, the structural damage of HF group was more evident compared with DHEA group. Conclusion DHEA may reduce the content of hepatic FFA in high-fat diet-induced obese rats via inhibiting the production of FFA and promoting theβ-oxidation of FFA.

Adiponectina determinaría el predominio de VLDL alteradas en el síndrome metabólico / Adiponectin would determine the predominance of altered VLDL in metabolic syndrome / Adiponectina iria determinar o predomínio de VLDL alteradas na síndrome metabólica

El objetivo del trabajo fue evaluar si la reducción de adiponectina (ADP) en el síndrome metabólico (SMet), influencia las características aterogénicas de VLDL. Se estudiaron 45 pacientes con SMet y 15 controles sanos. En suero en ayunas se midió perfil lipídico, ácidos grasos libres (AGL), ADP, se aisló VLDL (d<1,006 g/L) caracterizándola en su composición química y tamaño (HPLC-exclusión molecular). En plasma post-heparínico se determinó la actividad de lipoproteína lipasa (LPL). En SMet VLDL mostró incremento de masa, número de partículas, contenido en triglicéridos-VLDL y mayor proporción de VLDL grandes (p<0,05). El incremento de AGL correlacionó con la masa de VLDL (r=0,36; p=0,009), número de partículas-VLDL (r=0,45; p=0,0006) y %-VLDL grandes (r=0,32; p=0,02). SMet mostró descenso en ADP (7,4±4,8 vs. 15,5±7,2 μg/mL, p=0,01) y en actividad de LPL (p=0,01), que correlacionaron entre si (r=0,38; p=0,01; ajustado por HOMA-IR y cintura: β=0,35; p=0,02). ADP correlacionó negativamente con AGL y %-VLDL grandes (p<0,03). Se concluye que en SMet la disminución de ADP favorecería la secreción de VLDL sobre-enriquecidas en triglicéridos y de mayor tamaño, y además retardaría el catabolismo de VLDL mediado por LPL, resultando en la acumulación de VLDL alteradas en circulación con características aterogénicas.

The aim of the work was to evaluate whether the reduction of adiponectin (ADP) in metabolic syndrome (MetS) affects the atherogenic features of VLDL. A total of 45 patients with MetS (ATPIII) and 15 healthy controls were studied. In fasting serum, lipid profile, free fatty acids (FFA) and ADP were determined. VLDL was isolated (d<1.006 g/L) and characterized in chemical composition and size (size exclusion-HPLC). In post-heparin plasma, lipoprotein lipase (LPL) activity was measured. In MetS, VLDL showed increased total mass, particle number, VLDL-triglyceride content and higher large-VLDL proportion (p<0.05). The increase in FFA correlated with VLDL mass (r=0.36; p=0.009), VLDL particle number (r=0.45; p=0.0006) and large-VLDL proportion (r=0.32; p=0.02). MetS patients showed a decrease in ADP (7.4±4.8 vs. 15.5±7.2 μg/mL, p=0.01) and in LPL activity (p=0.01), that positively correlated between them (r=0.38; p=0.01; adjusted by HOMA-IR and waist: β=0.35; p=0.02). ADP inversely correlated with FFA and large-VLDL% (p<0.03). It can be concluded that in MetS, decreased ADP would favour the secretion of triglyceride over-enriched and larger VLDL particles, and also would delay VLDL catabolism mediated by LPL, resulting in the accumulation of altered VLDL with atherogenic characteristics.

O objetivo do trabalho foi avaliar se a redução da adiponectina (ADP) na síndrome metabólica (SM), afeta as características aterogênicas das VLDL. Foram estudados 45 indivíduos com SM e 15 controles saudáveis. Em jejum, foi medido em soro o perfil lipídico, ácidos graxos livres (AGL) e ADP. Foram isoladas as VLDL (d <1,006 g / L) caracterizando-as em relação a sua composição química e tamanho (HPLC- exclusão molecular). No plasma pós-heparina foi medida a atividade da lipoproteína lipase (LPL). Em indivíduos com SM, as VLDL apresentaram aumento de massa, número de partículas, conteúdo de triglicerídeos -VLDL e maior proporção de VLDL grandes (p<0,05). O aumento de AGL correlacionou com a massa de VLDL (r=0,36; p=0,009), número de partículas -VLDL (r=0,45; p=0,0006) e percentual -VLDL grandes (r=0,32; p=0,02). A SM mostrou uma diminuição em ADP (7,4±4,8 vs. 15,5±7,2 μg/mL, p=0,01) e em atividade de LPL (p=0,01), que correlacionaram entre eles (r=0,38; p=0,01; ajustada por HOMA-IR e cintura: β=0,35; p=0,02). A ADP correlacionou em forma negativa com AGL e %-VLDL grandes (p<0,03). A conclusão é que em indivíduos com SM, a diminuição da ADP iria favorecer a secreção de VLDL super-enriquecidas em triglicerídeos e de maior tamanho, e também atrasaria o catabolismo das VLDL mediado por LPL, resultando na acumulação de VLDL alteradas em circulação com características aterogênicas.

Effects of free fatty acids on catalytic activity of P450c17 in cultured NCI-H295R cells of adrenal gland / 中华内分泌代谢杂志

[Summary] The activities of 17α-hydroxylase and 17,20 lyase of cytochrome P450c17 were evaluated by ELISA in NCI-H295R cells after treatment with palmitate and oleate. The results showed that 0. 75 mmol/L plamitate did not influence the activity of 17α-hydroxylase, but increased the activity of 17, 20 lyase by 74. 3% ( P<0. 05). Oleate at the same concentration did not change the activity of 17,20 lyase. There were no significant changes in the protein expressions of P450c17, P450 oxidoreductase, and cytochrome b5 after treatment with palmitate and oleate. However,reactive oxygen species in cells were elevated by palmitate. The results suggest that exposure to palmitate may increase androgen production by inducing 17, 20 lyase activity of P450c17 in NCI-H295R cells, which is related with oxidative stress-mediated post-translational regulation of the enzyme.

Expression of ubiquitin editing enzyme A20 and its pathway in steatotic hepatocytes and monocytes / 中华消化杂志

Objective To investigate the changes of A20 expression stimulated by free fatty acids (FFA) and its pathway.Methods HepG2 cells and U937 cells were stimulated by 0.5 mmol/L mixed FFA.The expression of A20,phosphor-p65 and phosphor-IκBα of neclear factor (NF)-κB pathway and phosphor-c-Jun N-terminal kinase (JNK),JNK,phosphor-extracellular signal-regulated kinase (ERK),ERK,phosphor-p38 and p38 of mitogen-activated protein kinase (MAPK) pathway were detected by Western blotting.The level of interleukin (IL)-12p,IL-1β,tumor necrosis factor (TNF)-α,IL-6,IL-10 and IL-8 cytokines in the supernatant of cell culture were detected by flow cytometry.T-test was performed for statistical analysis.Results The level of A20 changed along with the stimulated time of FFA.NF-κB and MAPK pathways were activated after FFA stimulation.The secretion of IL-6 and IL-8 increased after HepG2 cells stimulated by FFA and both reached peak at 24 hour.Compared with control group,the difference in IL-8 was statistically significant ((423.8 ± 8.9) pg/mL vs (12.4 ± 4.5) pg/mL,t=41.28,P＜0.01).The difference in IL-6 was also statistically significant ((4 082±423.6) pg/mL vs (52.9±29.5) pg/mL,t=9.49,P＜0.01).After U937 cells were stimulated by FFA,the secretion of IL-8 increased compared with control group.And in a certain period of time the secretion was time dependence.The maximum secretion of 24 hours was (200.6±5.7) pg/mL vs (5.0±3.9) pg/mL,and the difference was statistically significant (t=28.16,P＜0.01).IL-10,IL-12p,IL-1β and TNF-α were detected.Both NF-κB pathway and MAPK pathway were detected.Conclusions The in vitro FFA mediated steatotic cell model could induce the expression change of A20 and secretion of inflammatory cytokines.NF-κB and MAPK pathways involved in the response to FFA in HepG2 cells and U937 cells.

Survey on serum free fatty acids levels in patients with hyperlipidemia / 国际检验医学杂志

Objective To explore the differences of serum free fatty acids (FFA)between the hyperlipidemia group and the healthy people with different ages and genders.Methods 912 healthy individuals of physical examination (healthy control group) and 1 061 patients with hyperlipidemia were selected and detected the serum FFA,total cholesterol,triglyceride,high density lipo-protein-cholesterol,low density lipoprotein-cholesterol,fasting plasma glucose and body mass index.The covariance analysis was used to investigate the differences in the level of serum FFA among different genders and age groups.The relationship between ser-um FFA and other serum lipids index in the patients with hyperlipidemia was analyzed by the multiple correlation analysis.Results The serum FFA level in the middle-aged females,middle-aged males and young males with hyperlipidemia was higher than that in the corresponding control groups;the serum FFA level in the young females with hyperlipidemia was lower than that in the other groups with hyperlipidemia;in the population groups with normal blood lipid,the serum FFA level in the old-age group was signifi-cantly higher than that in the middle-age and young group.Conclusion There is a difference in the serum FFA level in the hyperlip-idemia group with different ages and genders.

Influence of Fenofibrate on Apoptosis of Human Renal Proximal Tubular Cells Induced by Free Fatty Acids / 中国医科大学学报

Objective To explore the influence of fenofibrate on apoptosis of human renal proximal tubular cells(HK?2)induced by free fatty acid (FFAs). Methods Methyl azo thiazole blue(determined by MTT)was applied for detection of HK?2 cell proliferation capacity;Spectrophotometry was used to determine the expression of MDA and SOD;MCP?1 and IL?8 in culture supernatant of cells were detected by ELISA;Real?time PCR and Western blot were used to evaluate mRNA and protein expression of Bax and Bcl?2 respectively. Results FFAs inhibited HK?2 cell prolifera?tion in a dose and time dependence. mRNA and protein expression of Bax significantly increased compared with control,but mRNA and protein ex?pression of Bcl?2 decreased. After preincubation of fenofibrate,the inhibition of HK?2 cell proliferation by FFAs was alleviated;expression of SOD increased and expression of MDA,MCP?1 and IL?8 were decreased;mRNA and protein expression of Bax was significantly decreased,but mRNA and protein expression of Bcl?2 was increased. Conclusion FFAs can induce apoptosis of renal proximal tubular cell in a dose and time dependent manner. Fenofibrate can inhibite HK?2 cell apoptosis by decreasing oxidative stress,inhibiting inflammation,up?regulating expression of Bcl?2 and down?regulating expression of Bax,which alleviated nephrotoxicity of FFAs.

The investigation of the role of PKCδin free fatty acid-induced endothelial cell apoptosis / 重庆医学

Objective To investigate the role of PKCδin free fatty acid-induced endothelial cell apoptosis.Methods In addi-tion,we looked for evidence of apoptosis-related PKCδsignal pathway.Human umbilical vein endothelial cells were treated with va-rious concentrations of free fatty acids and transiently transfected with PKCδsiRNA to inhibit PKCδ expression.Cell proliferation was determined through colorimetric assays,and apoptosis was quantified using flow cytometry.Protein expression was determined from cell lysates use Western blots with antibodies against p-PKCδ Tyr512,PKCδ.Statistical analyses were performed.Results Free fatty acids had multiple effects on human umbilical vein endothelial cells,including concentration-dependent inhibition of cell proliferation,induction of apoptosis,increased Fas expression,and increased PKCδ expression and phosphorylation.Inhibition of PKCδmRNA expression by PKCδsiRNA led to a reduction in free fatty acid-induced apoptosis.Conclusion The free fatty acids-induced apoptosis in endothelial cells are possibly mediated by PKCδ.

Effects of Rosiglitazone on Body Weight,FPG,FFA and Other Indicators in Diabetes Model Rabbit / 中国药房

OBJECTIVE:To study the effects of rosiglitazone(RH)on body weight,FPG,FFA and other indicators in diabe-tes model rabbit. METHODS:18 rabbits were evenly randomized into control group,model group and dextran group. The latter 2 groups were given alloxan intravenously to induce diabetes model. 3 groups were given RH(0.5 mg/kg)intragastrically,and dex-tran group was additionally given dextran 40 glucose injection(5 ml/kg)intravenously,once a day,for consecutive 3 weeks. Body weight,serum level of FPG,FFA,AngⅡ and NO were determined before and after medication. RESULTS:Compared with be-fore medication,body weight of rabbits in control group were increased after medication,while the levels of FFA and AngⅡ were decreased;the levels of FPG and FFA were decreased in model group;body weight of rabbits were decreased in dextran group af-ter medication,with statistical significance (P0.05). The level of FFA in dextran group was higher than in model group after medication,with statistical significance(P<0.01). CONCLUSIONS:Rosiglitazone can lead to weight gain by a mechanism which reduce the level of FFA.

Mechanistic insights into pancreatic beta-cell mass regulation by glucose and free fatty acids / 대한해부학회지

Pancreatic islets are responsible for blood glucose homeostasis. Reduced numbers of functional (insulin-secreting) beta-cells in pancreatic islets underlies diabetes. Restoration of the secretion of the proper amount of insulin is a goal. Beta-cell mass is increased by neogenesis, proliferation and cell hypertrophy, and is decreased by beta-cell death primarily through apoptosis. Many hormones and nutrients affect beta-cell mass, and glucose and free fatty acid are thought to be the most important determinants of beta-cell equilibrium. A number of molecular pathways have been implicated in beta-cell mass regulation and have been studied. This review will focus on the role of the principle metabolites, glucose and free fatty acid, and the downstream signaling pathways regulating beta-cell mass by these metabolites.

Carcinogenicidad del D-004 en ratas Srague Dawley: informe parcial a los 18 meses / Carcinogenicity of D-004 in Sprague Dawley rats: a partial report at 18 months

INTRODUCCIÓN. el D-004, extracto lipídico del fruto de Roystonea regia (palma real), constituido por una mezcla reproducible de ácidos grasos -principalmente oleico, palmítico, láurico y mirístico- ha mostrado ser efectivo en modelos experimentales de hiperplasia prostática. OBJETIVO. resumir los resultados parciales (18 meses) del estudio de carcinogenicidad por exposición repetida y prolongada del D-004 en ratas Sprague Dawley, el cual culminará al concluir el tiempo establecido (24 meses). MÉTODOS. ratas Sprague Dawley de uno y otro sexo fueron distribuidas aleatoriamente en cuatro grupos (50 ratas/sexo/grupo): uno control de vehículo y tres tratados con D-004 (500, 1000 y 1500 mg/kg, respectivamente). Los tratamientos se administraron oralmente por intubación gástrica. Este reporte incluye los resultados de peso corporal, observaciones clínicas, mortalidad y frecuencia de aparición de tumores hasta ese momento (18 meses). RESULTADOS. la frecuencia de mortalidad es baja: en los grupos tratados fue de un 8,3 % por un 9 % en los controles. No se evidencia una disminución en el tiempo de supervivencia y las observaciones diarias no revelaron signos indicativos de toxicidad atribuibles al tratamiento. Además, el momento de aparición de tumores y la frecuencia de estos en los animales tratados y en los controles fueron estadísticamente similares en ambos sexos. CONCLUSIONES. en conclusión, la administración oral de D-004 (500-1500 mg/kg) a las ratas no mostró, durante los primeros 18 meses del estudio, evidencias de toxicidad o carcinogenicidad temprana relacionadas con el tratamiento

INTRODUCTION: D-004, a lipid extract from royal palm (Roystonea regia) fruit constituted by a reproducible mixture of fatty acids, mainly oleic, palmitic, lauric and myristic, has shown to be effective in experimental models of prostate hyperplasia. OBJECTIVE: summarize the partial results (18 months) of the study on carcinogenicity by repeated and long-term exposure of Sprague Dawley rats to D-004, to be completed in the planned period of 24 months. METHODS: sprague Dawley rats of both sexes were randomly distributed into four groups (50 rats / sex / group): one group was the vehicle control and three were treated with D-004 (500, 1000 and 1500 mg/kg, respectively). Treatments were administered orally by gastric intubation. This report includes the results obtained so far (18 months) concerning body weight, clinical observations, mortality and frequency of appearance of tumors. RESULTS: mortality is low: 8.3% in treatment groups and 9% in controls. A reduction in survival time was not observed, and daily observations did not reveal any signs of toxicity attributable to the treatment. The time of appearance and the frequency of tumors in treated animals and controls were statistically similar in both sexes. CONCLUSIONS: oral administration of D-004 (500­1500 mg/kg) to rats during the first 18 months of the study did not show any evidence of early carcinogenicity or toxicity associated with the treatment.