Long-chain acyl-Co A synthetase(ACSL) family members include five different ACSL isoforms, each encoded by a separate gene and have multiple spliced variants. ACSLs on endoplasmic reticulum and mitochondrial outer mem...Long-chain acyl-Co A synthetase(ACSL) family members include five different ACSL isoforms, each encoded by a separate gene and have multiple spliced variants. ACSLs on endoplasmic reticulum and mitochondrial outer membrance catalyze fatty acids with chain lengths from 12 to 20 carbon atoms to form acyl-Co As, which are lipid metabolic intermediates and involved in fatty acid metabolism, membrane modifications and various physiological processes. Gain- or lossof-function studies have shown that the expression of individual ACSL isoforms can alter the distribution and amount of intracellular fatty acids. Changes in the types and amounts of fatty acids, in turn, can alter the expression of intracellular ACSLs. ACSL family members affect not only the proliferation of normal cells, but the proliferation of malignant tumor cells. They also regulate cell apoptosis through different signaling pathways and molecular mechanisms. ACSL members have individual functions in fatty acid metabolism in different types of cells depending on substrate preferences, subcellular location and tissue specificity, thus contributing to liver diseases and metabolic diseases, such as fatty liver disease, obesity, atherosclerosis and diabetes. They are also linked to neurological disorders and other diseases. However, the mechanisms are unclear. This review addresses new findings in the classification and properties of ACSLs and the fatty acid metabolismassociated effects of ACSLs in diseases.展开更多
Long-chain acyl coenzyme A synthetase(ACSL) is a member of the synthetase family encoded by a multigene family;it plays an important role in the absorption and transport of fatty acid.Here we review the roles of ACSL ...Long-chain acyl coenzyme A synthetase(ACSL) is a member of the synthetase family encoded by a multigene family;it plays an important role in the absorption and transport of fatty acid.Here we review the roles of ACSL in the regulating absorption and transport of fatty acid,as well as the connection between ACSL and some metabolic diseases.展开更多
Fatty acids are energy substrates and cell components which participate in regulating signal transduction,transcription factor activity and secretion of bioactive lipid mediators.The acyl-CoA synthetases(ACSs)family c...Fatty acids are energy substrates and cell components which participate in regulating signal transduction,transcription factor activity and secretion of bioactive lipid mediators.The acyl-CoA synthetases(ACSs)family containing 26 family members exhibits tissue-specific distribution,distinct fatty acid substrate preferences and diverse biological functions.Increasing evidence indicates that dysregulation of fatty acid metabolism in the liver-gut axis,designated as the bidirectional relationship between the gut,microbiome and liver,is closely associated with a range of human diseases including metabolic disorders,inflammatory disease and carcinoma in the gastrointestinal tract and liver.In this review,we depict the role of ACSs in fatty acid metabolism,possible molecular mechanisms through which they exert functions,and their involvement in hepatocellular and colorectal carcinoma,with particular attention paid to long-chain fatty acids and small-chain fatty acids.Additionally,the liver-gut communication and the liver and gut intersection with the microbiome as well as diseases related to microbiota imbalance in the liver-gut axis are addressed.Moreover,the development of potentially therapeutic small molecules,proteins and compounds targeting ACSs in cancer treatment is summarized.展开更多
Fatty acid composition of four Sargassum species from Qingdao and Shidao,Shandong Provincewas investigated.16:0（palmitic acid）was the major saturated fatty acid.C<sub>18</sub> and C<sub>20</sub&...Fatty acid composition of four Sargassum species from Qingdao and Shidao,Shandong Provincewas investigated.16:0（palmitic acid）was the major saturated fatty acid.C<sub>18</sub> and C<sub>20</sub>were the mainpolyunsaturated fatty acids（PUFAs）.Arachidonic acid and eicosapentaenoic acid predominated amongpolyenoic acids in all the algal species examined.except for Sargassum sp.which had low concentrationof eicosapentaenoic acid.展开更多
The feeding trial was conducted to determine the effects of flaxseed on layer＇s performance and egg quality, and the effects of the dietary ratio of ω-6 fatty acid to ω-3 fatty acid on fatty acid deposition in yolk...The feeding trial was conducted to determine the effects of flaxseed on layer＇s performance and egg quality, and the effects of the dietary ratio of ω-6 fatty acid to ω-3 fatty acid on fatty acid deposition in yolk using flaxseed as resource of ω-3 fatty acid and sunflower seed as resource of ω-6 fatty acid. 192 20-wk-old Newroman commercial hens were randomly divided into 4 treatment groups with 6 replicates containing 8 birds. The rations corresponding with the four treatments were formulated with 4% flaxseed ＋ 9% sunflower seed, 8% flaxseed ＋ 18% sunflower seed, 15% flaxseed, and soybean meal, respectively. Sunflower seed was unshelled and flaxseed was whole. Ratios of ω-6 fatty acid to ω-3 fatty acid in 4 dietary treatments were 5.67, 5.21, 1.07, and 11.83, respectively. It can be concluded that long-term feeding 15% flaxseed had no significant （P〉 0.05） influence on egg production, egg weight, eggshell quality, yolk weight, and percentage of yolk weight. Dietary ratio of ω-6 fatty acid to ω-3 fatty acid had impact on the 0-3 fatty acid levels in yolk, nevertheless yolk fatty acid profiles were different from those of dietary fatty acid compositions.展开更多
Objective： To determine fatty acid synthase （FAS） expression in human multiple myeloma and verify its potential as a therapeutic target in multiple myeloma. Methods： FAS expression was determined by immunohistoche...Objective： To determine fatty acid synthase （FAS） expression in human multiple myeloma and verify its potential as a therapeutic target in multiple myeloma. Methods： FAS expression was determined by immunohistochemistry, reverse-transcription polymerase chain reaction （RT-PCR） and immunoblot analysis in bone marrow samples obtained from 27 patients with multiple myeloma （MM patients） and peripheral blood mononuclear cells （PBMCs） obtained from 12 healthy donors In parallel, additional analyses were performed on 2 human multiple myeloma cell lines, U266 and RPM18226. U266 cells were treated with cerulenin at various concentrations （5 to 320 μg/ml） for 24 h, and metabolic activity was measured by 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide （MTT） assays. Apoptosis was evaluated by dual Annexin V/Pl （propidium iodide） labeling and flow cytometry （FCM） in U266 cells treated with 20 μg/ml cerulenin for 12 h or 24 h. Results： By immunohistochemistry, we found that 19 of 27 bone marrow samples obtained from MM patients expressed significantly high levels of FAS. Similarly, by RT-PCR, 22 of 27 bone marrow samples obtained from MM patients, U266 and RPM18226 showed FAS expression, whereas PBMC samples from 12 healthy donors did not express detectable level of FAS. FAS protein expression was confirmed by immunoblot analysis in 16 of 27 bone marrow samples obtained from MM patients, U266 and RPM18226 cell lines, and no FAS protein expression was detected in PBMC samples from 12 healthy donors. U266 cells were highly sensitive to cerulenin treatment, with a dosage-related effect on metabolic activity, as a measure for cell proliferation. U266 cells treated with 20 μg/ml cerulenin for 12 and 24 h also showed early sign of apoptosis with 56.9% and 69.3% Annexin V^＋/Pl cells, and late apoptotic and necrotic cells with 3.2% and 17.6% Annexin V^＋/Pl^＋ cells. Conclusion： Increased FAS expression existed in multiple myeloma samples and human myeloma cell lines. Cerulenin greatly inhibited metabolic activity/cell proliferation of U266 cells and induced apoptosis, suggesting that FAS is an effective target for pharmacological therapy in human multiple myeloma.展开更多
Fatty acids(FAs) provide energy and also can be used to trace trophic relationships among organisms.Sea cucumber Apostichopus japonicus goes into a state of aestivation during warm summer months.We examined fatty acid...Fatty acids(FAs) provide energy and also can be used to trace trophic relationships among organisms.Sea cucumber Apostichopus japonicus goes into a state of aestivation during warm summer months.We examined fatty acid profiles in aestivated and non-aestivated A.japonicus using multivariate analyses(PERMANOVA,MDS,ANOSIM,and SIMPER).The results indicate that the fatty acid profiles of aestivated and non-aestivated sea cucumbers differed significantly.The FAs that were produced by bacteria and brown kelp contributed the most to the differences in the fatty acid composition of aestivated and nonaestivated sea cucumbers.Aestivated sea cucumbers may synthesize FAs from heterotrophic bacteria during early aestivation,and long chain FAs such as eicosapentaenoic(EPA) and docosahexaenoic acid(DHA) that produced from intestinal degradation,are digested during deep aestivation.Specific changes in the fatty acid composition of A.japonicus during aestivation needs more detailed study in the future.展开更多
目的观察3种神经细胞保护措施对缺氧缺血性脑损伤新生大鼠脑组织凋亡相关因子及其配体(Fas和FasL)基因表达的影响。方法选择120只7日龄Wistar大鼠,按随机数字表法将大鼠分为神经干细胞组、促红细胞生成素(EPO)组、ω-3不饱和脂肪酸组、...目的观察3种神经细胞保护措施对缺氧缺血性脑损伤新生大鼠脑组织凋亡相关因子及其配体(Fas和FasL)基因表达的影响。方法选择120只7日龄Wistar大鼠,按随机数字表法将大鼠分为神经干细胞组、促红细胞生成素(EPO)组、ω-3不饱和脂肪酸组、缺氧缺血性脑损伤模型组,每组30只。神经干细胞组、EPO组、ω-3不饱和脂肪酸组于制模后经尾静脉注射5 mL神经干细胞、EPO、ω-3不饱和脂肪酸.缺氧缺血性脑损伤模型组给予等量生理盐水给药后6.12、24、48、72 h 5个时间点各组处死6只大鼠取海马组织.测定大脑海马组织Fas/FasL的基因表达,以及Toll样受体4(TLR4)、核转录因子-κB(NF-κB)、肿瘤坏死因子-α(TNF-α)、白细胞介素(IL-1β、IL-6)的蛋白表达水平和细胞凋亡率。结果①mRNA表达:3个实验组给药后Fas和FasL的mRNA表达均较缺氧缺血性脑损伤模型组显著降低,以给药后24h降低最为显著,且神经干细胞组VEPO组<ω-3不饱和脂肪酸组<缺氧缺血性脑损伤模型组〔FasmRNA表达(2^-△△Ct):140.5±2.9、156.4±2.5.165.2±2.7比173.7±2.8,FasL mRNA表达(2^-△△Ct):143.1±4.3、154.6±1.5,160.7±1.4比174.7±2.8],各组间比较差异均有统计学意义(均P<0.05)。②蛋白表达:3个实验组给药后海马组织TLR4、NF-κB、TNF-α、IL-1β、IL-6的蛋白表达水平均较缺氧缺血性脑损伤模型组显著降低(TLR4/GAPDH:0.7±0.2,0.6±0.1、0.2±0.1比1.4±0.1;NF-κB/GAPDH:6.7±0.4,5.3±0.1、1.1±0.2比11.2±0.3;TNF-α/GAPDH:14.3±1.4、11.2±1.2、3.2±2.1比23.2±0.5;IL-1β/GAPDH:9.4±0.2,7.4±0.3,2.2±0.3比13.4±0.1;IL-6/GAPDH:36.2±4.4.39.3±1.5、26.2±2.1比51.4±1.4,均P<0.05).神经干细胞组上述指标的蛋白表达水平VEPO组<ω-3不饱和脂肪酸组<缺氧缺血性脑损伤模型组:③细胞凋亡率:ω-3不饱和脂肪酸组、EPO组、神经干细胞组给药后海马组织细胞凋亡率均明显低于缺氧缺血性脑损伤模型组〔(3.7±0.3)%、(3.4±0.2)%、(2.5±0.1)%比(5.5±0.4)%,均P<0.05〕。结论缺氧缺血性脑损伤新生大鼠脑组织Fas和FasLmRNA呈高表达;而给予神经干细胞、EPO及ω-3不饱和脂肪酸处理均能减少脑组织Fas和FasL的mRNA表达.展开更多
基金Supported by National Natural Science Foundation of China,No.81373465
文摘Long-chain acyl-Co A synthetase(ACSL) family members include five different ACSL isoforms, each encoded by a separate gene and have multiple spliced variants. ACSLs on endoplasmic reticulum and mitochondrial outer membrance catalyze fatty acids with chain lengths from 12 to 20 carbon atoms to form acyl-Co As, which are lipid metabolic intermediates and involved in fatty acid metabolism, membrane modifications and various physiological processes. Gain- or lossof-function studies have shown that the expression of individual ACSL isoforms can alter the distribution and amount of intracellular fatty acids. Changes in the types and amounts of fatty acids, in turn, can alter the expression of intracellular ACSLs. ACSL family members affect not only the proliferation of normal cells, but the proliferation of malignant tumor cells. They also regulate cell apoptosis through different signaling pathways and molecular mechanisms. ACSL members have individual functions in fatty acid metabolism in different types of cells depending on substrate preferences, subcellular location and tissue specificity, thus contributing to liver diseases and metabolic diseases, such as fatty liver disease, obesity, atherosclerosis and diabetes. They are also linked to neurological disorders and other diseases. However, the mechanisms are unclear. This review addresses new findings in the classification and properties of ACSLs and the fatty acid metabolismassociated effects of ACSLs in diseases.
基金Supported by the National Natural Science Foundation of China(81373465)
文摘Long-chain acyl coenzyme A synthetase(ACSL) is a member of the synthetase family encoded by a multigene family;it plays an important role in the absorption and transport of fatty acid.Here we review the roles of ACSL in the regulating absorption and transport of fatty acid,as well as the connection between ACSL and some metabolic diseases.
基金Supported by the Interdisziplinäres Zentrum für Klinische Forschung(IZKF-MSP-06)of University Hospital Jena.
文摘Fatty acids are energy substrates and cell components which participate in regulating signal transduction,transcription factor activity and secretion of bioactive lipid mediators.The acyl-CoA synthetases(ACSs)family containing 26 family members exhibits tissue-specific distribution,distinct fatty acid substrate preferences and diverse biological functions.Increasing evidence indicates that dysregulation of fatty acid metabolism in the liver-gut axis,designated as the bidirectional relationship between the gut,microbiome and liver,is closely associated with a range of human diseases including metabolic disorders,inflammatory disease and carcinoma in the gastrointestinal tract and liver.In this review,we depict the role of ACSs in fatty acid metabolism,possible molecular mechanisms through which they exert functions,and their involvement in hepatocellular and colorectal carcinoma,with particular attention paid to long-chain fatty acids and small-chain fatty acids.Additionally,the liver-gut communication and the liver and gut intersection with the microbiome as well as diseases related to microbiota imbalance in the liver-gut axis are addressed.Moreover,the development of potentially therapeutic small molecules,proteins and compounds targeting ACSs in cancer treatment is summarized.
文摘Fatty acid composition of four Sargassum species from Qingdao and Shidao,Shandong Provincewas investigated.16:0（palmitic acid）was the major saturated fatty acid.C<sub>18</sub> and C<sub>20</sub>were the mainpolyunsaturated fatty acids（PUFAs）.Arachidonic acid and eicosapentaenoic acid predominated amongpolyenoic acids in all the algal species examined.except for Sargassum sp.which had low concentrationof eicosapentaenoic acid.
基金supported by the Heilongjiang Province Government Foundation,China(HL-98)
文摘The feeding trial was conducted to determine the effects of flaxseed on layer＇s performance and egg quality, and the effects of the dietary ratio of ω-6 fatty acid to ω-3 fatty acid on fatty acid deposition in yolk using flaxseed as resource of ω-3 fatty acid and sunflower seed as resource of ω-6 fatty acid. 192 20-wk-old Newroman commercial hens were randomly divided into 4 treatment groups with 6 replicates containing 8 birds. The rations corresponding with the four treatments were formulated with 4% flaxseed ＋ 9% sunflower seed, 8% flaxseed ＋ 18% sunflower seed, 15% flaxseed, and soybean meal, respectively. Sunflower seed was unshelled and flaxseed was whole. Ratios of ω-6 fatty acid to ω-3 fatty acid in 4 dietary treatments were 5.67, 5.21, 1.07, and 11.83, respectively. It can be concluded that long-term feeding 15% flaxseed had no significant （P〉 0.05） influence on egg production, egg weight, eggshell quality, yolk weight, and percentage of yolk weight. Dietary ratio of ω-6 fatty acid to ω-3 fatty acid had impact on the 0-3 fatty acid levels in yolk, nevertheless yolk fatty acid profiles were different from those of dietary fatty acid compositions.
基金Project supported by the Medicine and Health Research Fund of Zhejiang Province(No.2007B091)the Office of Education of Zhejiang Province,China(No.20070104)
文摘Objective： To determine fatty acid synthase （FAS） expression in human multiple myeloma and verify its potential as a therapeutic target in multiple myeloma. Methods： FAS expression was determined by immunohistochemistry, reverse-transcription polymerase chain reaction （RT-PCR） and immunoblot analysis in bone marrow samples obtained from 27 patients with multiple myeloma （MM patients） and peripheral blood mononuclear cells （PBMCs） obtained from 12 healthy donors In parallel, additional analyses were performed on 2 human multiple myeloma cell lines, U266 and RPM18226. U266 cells were treated with cerulenin at various concentrations （5 to 320 μg/ml） for 24 h, and metabolic activity was measured by 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide （MTT） assays. Apoptosis was evaluated by dual Annexin V/Pl （propidium iodide） labeling and flow cytometry （FCM） in U266 cells treated with 20 μg/ml cerulenin for 12 h or 24 h. Results： By immunohistochemistry, we found that 19 of 27 bone marrow samples obtained from MM patients expressed significantly high levels of FAS. Similarly, by RT-PCR, 22 of 27 bone marrow samples obtained from MM patients, U266 and RPM18226 showed FAS expression, whereas PBMC samples from 12 healthy donors did not express detectable level of FAS. FAS protein expression was confirmed by immunoblot analysis in 16 of 27 bone marrow samples obtained from MM patients, U266 and RPM18226 cell lines, and no FAS protein expression was detected in PBMC samples from 12 healthy donors. U266 cells were highly sensitive to cerulenin treatment, with a dosage-related effect on metabolic activity, as a measure for cell proliferation. U266 cells treated with 20 μg/ml cerulenin for 12 and 24 h also showed early sign of apoptosis with 56.9% and 69.3% Annexin V^＋/Pl cells, and late apoptotic and necrotic cells with 3.2% and 17.6% Annexin V^＋/Pl^＋ cells. Conclusion： Increased FAS expression existed in multiple myeloma samples and human myeloma cell lines. Cerulenin greatly inhibited metabolic activity/cell proliferation of U266 cells and induced apoptosis, suggesting that FAS is an effective target for pharmacological therapy in human multiple myeloma.
基金Supported by the National Marine Public Welfare Research Project(No.201305043)the National Natural Science Foundation of China(No.41106134)the National Key Technology R&D Program of China(Nos.2011BAD13B02,2010BAC68B01)
文摘Fatty acids(FAs) provide energy and also can be used to trace trophic relationships among organisms.Sea cucumber Apostichopus japonicus goes into a state of aestivation during warm summer months.We examined fatty acid profiles in aestivated and non-aestivated A.japonicus using multivariate analyses(PERMANOVA,MDS,ANOSIM,and SIMPER).The results indicate that the fatty acid profiles of aestivated and non-aestivated sea cucumbers differed significantly.The FAs that were produced by bacteria and brown kelp contributed the most to the differences in the fatty acid composition of aestivated and nonaestivated sea cucumbers.Aestivated sea cucumbers may synthesize FAs from heterotrophic bacteria during early aestivation,and long chain FAs such as eicosapentaenoic(EPA) and docosahexaenoic acid(DHA) that produced from intestinal degradation,are digested during deep aestivation.Specific changes in the fatty acid composition of A.japonicus during aestivation needs more detailed study in the future.
文摘目的观察3种神经细胞保护措施对缺氧缺血性脑损伤新生大鼠脑组织凋亡相关因子及其配体(Fas和FasL)基因表达的影响。方法选择120只7日龄Wistar大鼠,按随机数字表法将大鼠分为神经干细胞组、促红细胞生成素(EPO)组、ω-3不饱和脂肪酸组、缺氧缺血性脑损伤模型组,每组30只。神经干细胞组、EPO组、ω-3不饱和脂肪酸组于制模后经尾静脉注射5 mL神经干细胞、EPO、ω-3不饱和脂肪酸.缺氧缺血性脑损伤模型组给予等量生理盐水给药后6.12、24、48、72 h 5个时间点各组处死6只大鼠取海马组织.测定大脑海马组织Fas/FasL的基因表达,以及Toll样受体4(TLR4)、核转录因子-κB(NF-κB)、肿瘤坏死因子-α(TNF-α)、白细胞介素(IL-1β、IL-6)的蛋白表达水平和细胞凋亡率。结果①mRNA表达:3个实验组给药后Fas和FasL的mRNA表达均较缺氧缺血性脑损伤模型组显著降低,以给药后24h降低最为显著,且神经干细胞组VEPO组<ω-3不饱和脂肪酸组<缺氧缺血性脑损伤模型组〔FasmRNA表达(2^-△△Ct):140.5±2.9、156.4±2.5.165.2±2.7比173.7±2.8,FasL mRNA表达(2^-△△Ct):143.1±4.3、154.6±1.5,160.7±1.4比174.7±2.8],各组间比较差异均有统计学意义(均P<0.05)。②蛋白表达:3个实验组给药后海马组织TLR4、NF-κB、TNF-α、IL-1β、IL-6的蛋白表达水平均较缺氧缺血性脑损伤模型组显著降低(TLR4/GAPDH:0.7±0.2,0.6±0.1、0.2±0.1比1.4±0.1;NF-κB/GAPDH:6.7±0.4,5.3±0.1、1.1±0.2比11.2±0.3;TNF-α/GAPDH:14.3±1.4、11.2±1.2、3.2±2.1比23.2±0.5;IL-1β/GAPDH:9.4±0.2,7.4±0.3,2.2±0.3比13.4±0.1;IL-6/GAPDH:36.2±4.4.39.3±1.5、26.2±2.1比51.4±1.4,均P<0.05).神经干细胞组上述指标的蛋白表达水平VEPO组<ω-3不饱和脂肪酸组<缺氧缺血性脑损伤模型组:③细胞凋亡率:ω-3不饱和脂肪酸组、EPO组、神经干细胞组给药后海马组织细胞凋亡率均明显低于缺氧缺血性脑损伤模型组〔(3.7±0.3)%、(3.4±0.2)%、(2.5±0.1)%比(5.5±0.4)%,均P<0.05〕。结论缺氧缺血性脑损伤新生大鼠脑组织Fas和FasLmRNA呈高表达;而给予神经干细胞、EPO及ω-3不饱和脂肪酸处理均能减少脑组织Fas和FasL的mRNA表达.
