Objective:Our aim was to test the hypothesis that fatty acid synthase(FASN)expression contributes to radioresistance of nasopharyngeal carcinoma(NPC)cells and that inhibiting FASN enhances radiosensitivity.Methods:Tar...Objective:Our aim was to test the hypothesis that fatty acid synthase(FASN)expression contributes to radioresistance of nasopharyngeal carcinoma(NPC)cells and that inhibiting FASN enhances radiosensitivity.Methods:Targeting FASN using epigallocatechin gallate(EGCG)or RNA interference in NPC cell lines that overexpress endogenous FASN was performed to determine their effects on cellular response to radiationin vitro using MTT and colony formation assays,andin vivo using xenograft animal models.Western blot,immunohistochemistry,real-time PCR arrays,and real-time RT-PCR were used to determine the relationship between FASN and frizzled class receptor 10(FZD10)expression.FZD10 knockdown and overexpression were used to determine its role in mediating FASN function in cellular response to radiation.Immunohistochemical staining was used to determine FASN and FZD10 expressions in human NPC tissues,followed by analysis of their association with the overall survival of patients.Results:FASN knockdown or inhibition significantly enhanced radiosensitivity of NPC cells,bothin vitro andin vivo.There was a positive association between FASN and FZD10 expression in NPC cell lines grown as monolayers or xenografts,as well as human tissues.FASN knockdown reduced FZD10 expression,and rescue of FZD10 expression abolished FASN knockdown-induced enhancement of radiosensitivity.FASN and FZD10 were both negatively associated with overall survival of NPC patients.Conclusions:FASN contributes to radioresistance,possiblyvia FZD10 in NPC cells.Both FZD10 and FASN expressions were associated with poor outcomes of NPC patients.EGCG may sensitize radioresistance by inhibiting FASN and may possibly be developed as a radiosensitizer for better treatment of NPCs.展开更多
Background: The liver is the corner stone in lipid metabolism, free fatty acid uptake, synthesizing, storing and exporting lipids;non-alcoholic fatty liver disease (NAFLD) develops if there is any interruption or dera...Background: The liver is the corner stone in lipid metabolism, free fatty acid uptake, synthesizing, storing and exporting lipids;non-alcoholic fatty liver disease (NAFLD) develops if there is any interruption or derangements in lipid metabolim. Fatty acid synthase (FAS) is the major enzyme in lipogenesis, and its circulating level is a bi-omarker of metabolically demanding human diseases. Aim of the Work: To evaluate the level of circulating FAS in NAFLD patients and to correlate it to serum lipid pa-rameters. Materials and Methods: The study included forty NAFLD patients and forty age and sex-matched healthy subjects as controls. Results: FAS levels were signifi-cantly higher in NAFLD patients compared to their level in the controls (P < 0.05). Ad-ditionally, a positive correlation was found between the levels of FAS and BMI (r = 0.57), and between FAS levels and triglycerides and low density lipoprotein cholesterol levels in NAFLD patients (r = 0.79 & 0.53, respectively). Conclusion: Elevated levels of circulating FAS can be considered as a biomarker of fatty liver disease.展开更多
Fatty acid synthase (FAS) is a multifunctional enzyme that plays an important role in the formation of fatty acids. The fatty acids take part in many processes, such as cell signaling and energy metabolism, and in ins...Fatty acid synthase (FAS) is a multifunctional enzyme that plays an important role in the formation of fatty acids. The fatty acids take part in many processes, such as cell signaling and energy metabolism, and in insects they are important in both cuticular hydrocarbon (CHC) formation and reproduction. Here we characterized the sequence structure and function of an FAS from the small brown planthopper (SBPH), Laodelphax striatellus. The full-length open reading frame (ORF) sequence of LsFAS1 was 7122 bp, encoding a predicted protein of 2373 amino acid residues. There were 7 functional domains in the LsFAS1 protein sequence. Gene expression screening by real-time quantitative polymerase chain reaction (RT-qPCR) showed that LsFAS1 was expressed in all developmental stages. Relative expression was highest at the 4th-instar and female adult stages. Among different tissues, the expression level of LsFAS1 in the ovary was the highest. Phylogenetic analysis showed that LsFAS1 clustered in a clade with 2 FASs from Nilaparvata lugens. Furthermore, these 3 FASs are related to cockroach BgFAS and locust LmFAS. After RNA interference-mediated knock-down, most treated insects died at eclosion. In addition, the lifespan of dsFAS1-treated female adults was shorter than that of the dsGFP-injected control, and offspring production decreased. Also, the expression of vitellogenin (Vg) and vitellogenin receptor (VgR) genes decreased. Virgin females dissected at days 2 and 4 post-eclosion showed many matured oocytes in planthoppers treated with dsGFP but not with dsFAS1. These data highlight the importance of LsFAS1 in SBPH, including a role in reproduction.展开更多
OBJECTIVE: To study the mechanism of Dangfei Liganning capsule(当飞利肝宁胶囊) in the treatment of rats with metabolic associated fatty liver disease(MAFLD). METHODS: Totally 48 specific pathogen free SpragueDawley ma...OBJECTIVE: To study the mechanism of Dangfei Liganning capsule(当飞利肝宁胶囊) in the treatment of rats with metabolic associated fatty liver disease(MAFLD). METHODS: Totally 48 specific pathogen free SpragueDawley male rats were randomly divided into normal Group, model group, Dangfei Liganning high, moderate, and low-dose groups and Essentiale group which were fed with high fat diet for 8 weeks, and gavage and molding were carried out simultaneously. Dangfei Liganning high, middle and low-dose group were given 0.27, 0.135 and 0.0675 g·kg-1·d-1 respectively by gavage, Essentiale group was given 0.123 g·kg-1·d-1 by gavage, the same amount of distilled water was given by gavage in the normal group and the model group. The rats were weighed at the 0th week, 2nd week, 4th week, 6th week and 8th weekend respectively. The rats were sacrificed at the end of the 8th week. Serum levels of alanine aminotransferase(ALT), alanine aminotransferase(AST),triglyceride(TG), total cholesterol(CHO), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein (LDL-C), total protein(TP), albumin(Alb), globulin(GLB), total bilirubin(TBIL), direct bilirubin(DBIL), tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) were measured. The levels of liver tumor necrosis factor-α(TNF-α), interleukin-6(IL-6) and liver pathology [hematoxylin and eosin(HE) staining, oil red O staining] were detected. The expression levels of liver X receptor α(LXRα), steroid regulatory element binding protein-1(SREBP-1) and fatty acid synthase(FAS) were detected by immunohistochemistry, Western blot and reverse transcription-polymerase chain reaction reverse transcription-polymerase chain reaction. RESULTS: From the beginning to the 8th week, the growth rate of body weight in the Dangfei Liganning highdose group was slower than all other groups. There was no significant difference in ALB level in all groups(P > 0.05). Compared with the model group, the levels of ALT, AST, LDL-C, TG, CHO, TP, GLB, TBIL, DBIL, IL-6, TNF-α were significantly decreased and HDL-C were significantly increased in Dangfei Liganning high-dose group(P < 0.01, < 0.05). HE and oil red O staining showed that the fatty lesions in rat liver were alleviated, while the expressions of LXRα, SREBP-1, FAS m RNA and protein were significantly decreased(P < 0.01). CONCLUSIONS: Dangfei Liganning capsule can slow down the increase of body weight of MAFLD rats, reduce the levels of transaminase, Lipid and inflammatory factors in MAFLD rats, promote the synthesis of liver protein and bile metabolism, and improve the liver fatty lesion of MAFLD rats, among which the Dangfei Liganning highdose group is more effective. The mechanism of action may be through blocking LXR-SREBP-1-FAS signal pathway.展开更多
SARS-CoV-2 is an emerging viral pathogen and a major global public health challenge since December of 2019, with limited effective treatments throughout the pandemic.As part of the innate immune response to viral infe...SARS-CoV-2 is an emerging viral pathogen and a major global public health challenge since December of 2019, with limited effective treatments throughout the pandemic.As part of the innate immune response to viral infection, type Ⅰ interferons(IFN-Ⅰ) trigger a signaling cascade that culminates in the activation of hundreds of genes, known as interferon stimulated genes(ISGs), that collectively foster an antiviral state.We report here the identification of a group of type Ⅰ interferon suppressed genes,including fatty acid synthase(FASN), which are involved in lipid metabolism.Overexpression of FASN or the addition of its downstream product, palmitate, increased viral infection while knockout or knockdown of FASN reduced infection.More importantly, pharmacological inhibitors of FASN effectively blocked infections with a broad range of viruses, including SARS-CoV-2 and its variants of concern.Thus, our studies not only suggest that downregulation of metabolic genes may present an antiviral strategy by type Ⅰ interferon, but they also introduce the potential for FASN inhibitors to have a therapeutic application in combating emerging infectious diseases such as COVID-19.展开更多
Background Estrogen deficiency contributes to postmenopausal osteoporosis. Periosteum might be a potential target of estrogen, but the underlying mechanism at gene level is far from being elucidated. The objective of ...Background Estrogen deficiency contributes to postmenopausal osteoporosis. Periosteum might be a potential target of estrogen, but the underlying mechanism at gene level is far from being elucidated. The objective of this study was to investigate the correlation between estrogen and fatty acid synthase (FAS) expression in periosteum. Methods Human periosteum cells were cultured in vitro. Expressed genes in the substrated cDNA library were verified using semi-quantitative PCR and real-time PCR. The expression of FAS in periosteum of ovarectomized (OVX) SD rats was investigated. Results FAS gene was most significantly expressed in the subtracted cDNA library of periosteal cells screened by semi-quantitative PCR. Low FAS expression was verified by real-time PCR in the estrogen exposed human periosteum rather than in the control. The estradiol levels were (20.81±12.62) pg/ml, (19.64±4.35) pg/ml and (13.47±1.84) pg/ml in the sham group, the control, and the OVX group, respectively. The estradiol levels in the OVX group was significantly lower (P=-0.0386). The FAS gene expression in periosteum in the OVX group, sham group, and control group was 3.09±1.97, 1.33±0.47 and 1.51±1.32, respectively. The gene expression in the OVX group was significantly higher (P=0.0372). Conclusion Estrogen modulates FAS gene expression in in vitro human perisoteum as well as in in vivo rat periosteum.展开更多
Dietary macronutrients and micronutrients play important roles in human health.On the other hand,the excessive energy derived from food is stored in the form of triacylglycerol.A variety of dietary and hormonal factor...Dietary macronutrients and micronutrients play important roles in human health.On the other hand,the excessive energy derived from food is stored in the form of triacylglycerol.A variety of dietary and hormonal factors affect this process through the regulation of the activities and expression levels of those key player enzymes involved in fatty acid biosynthesis such as acetyl-CoA carboxylase,fatty acid synthase,fatty acid elongases,and desaturases.As a micronutrient,vitamin A is essential for the health of humans.Recently,vitamin A has been shown to play a role in the regulation of glucose and lipid metabolism.This review summarizes recent research progresses about the roles of vitamin A in fatty acid synthesis.It focuses on the effects of vitamin A on the activities and expression levels of mRNA and proteins of key enzymes for fatty acid synthesis in vitro and in vivo.It appears that vitamin A status and its signaling pathway regulate the expression levels of enzymes involved in fatty acid synthesis.Future research directions are also discussed.展开更多
The effects and the mechanism of insulin treatment on intracellular lipid metabolism in liver of diabetic rats were evaluated. Type 2 diabetic rats were induced by injecting the streptozotocin (25 mg/kg) and fat ric...The effects and the mechanism of insulin treatment on intracellular lipid metabolism in liver of diabetic rats were evaluated. Type 2 diabetic rats were induced by injecting the streptozotocin (25 mg/kg) and fat rich food. According to the results of oral glucose tolerance test (OGTT) and glucose-induced insulin secretion test (IRT), the rats were divided into two groups: untreated group (UT) and insulin-treated group (IT). Normal rats (NC) served as controls. The treatment with either Humulin N (4-6 U/kg every day), or saline lasted for 4 weeks. Body weight, OGTT, IRT, blood lipids, intracellular lipids in liver, hepatic fatty acid oxidation and the activity of fatty acid synthase (FAS) were detected. The change of liver histology was observed. The insulin sensitivity index (ISI) was applied to assess the status of insulin resistance. The results showed that as compared with NC group, the plasma and hepatic intracellular Triglyceride (TG), total cholesterol (TC) and free fatty acids (FFAs) were increased significantly in UT group (P〈0.05), and lipid droplets could be seen dispersedly in the liver specimens, the hepatic fatty acid oxidation was increased markedly (P〈0.05), while the fatty acid synthase activity decreased (P〈0.05). Insulin treatment resulted in a further accumulation of lipids in liver by 55.7 %, 19.87 % and 22.2 % increase in TG, TC, FFAs respectively. The size of hepatocytes was enlarged and the cells were filled with fat drops. Plasma lipids showed little decrease and still significantly higher than those in NC group after the insulin treatment. Meanwhile, insulin treatment was companied by 20 % decrease in the rate of fatty acid oxidation and 31 % increase in hepatic FAS activity compared to, UT group. It was concluded that treatment with insulin on type 2 diabetic rat increases hepatic intracellular lipid accumulation by inhibiting hepatic fatty acid oxidation and activating FAS.展开更多
Water retention is critical for physiological homeostasis and survival in terrestrial insects. While deposition of hydrocarbons on insect cuticles as a key measure for water conservation has been extensively investiga...Water retention is critical for physiological homeostasis and survival in terrestrial insects. While deposition of hydrocarbons on insect cuticles as a key measure for water conservation has been extensively investigated, we know little about other mechanisms for preventing water loss in insects. Here, we report two fatty acid synthetic genes that are independent of hydrocarbon production but crucial for water retention in the German cockroach Blattella germanica (L.). First, an integument enriched fatty acid elongase gene (BgElo1) was identified as a critical gene for desiccation resistance in B. germanica;however, knockdown of BgElo1 surprisingly failed to cause a decline in cuticular lipids. In addition, RNA interference (RNAi)-knockdown of an upstream fatty acid synthase gene (BgFas3) showed a similar phenotype, and transmission electron microscopy analysis revealed that BgFas3- or BgElo1-RNAi did not affect cuticle architecture. Bodyweight loss test showed that repression of BgFas3 and BgElo1 significantly increased the weight loss rate, but the difference disappeared when the respiration was closed by freeze killing the cockroaches. A water immersion test was performed, and we found that BgFas3- and BgElo1-RNAi made it difficult for cockroaches to recover from drowning, which was supported by the upregulation of hypoxia-related genes after a 10-h recovery from drowning. Moreover, a dyeing assay with water-soluble Eosin Y showed that this was caused by the entry of water into the respiratory system. Our research suggests that BgFas3 and BgElo1 are required for both inward and outward waterproofing of the respiratory system. This study benefits the understanding of water retention mechanisms in insects.展开更多
Goat milk is widely recognized for its nutritional value.Fatty acid synthase(FAS)is the crucial enzyme of fatty acid de novo synthesis.It plays an important role in the formation of goat milk fat.In this paper,we firs...Goat milk is widely recognized for its nutritional value.Fatty acid synthase(FAS)is the crucial enzyme of fatty acid de novo synthesis.It plays an important role in the formation of goat milk fat.In this paper,we first introduced the molecular regulation process of goat milk fat metabolism based on the structure research of FAS.Secondly,we reviewed some key factors in FAS transcription and post-transcriptional regulation of the goat mammary gland and preliminarily constructed the expression network of the goat mammary gland FAS gene.The purpose of this paper is to systematically introduce the role of FAS in goat milk fat metabolism and to provide a reference for future studies on the mechanism of goat milk fat metabolism.展开更多
A new series compounds, α-methylene-β-carboxy-γ-thiobutyrolactones, have been prepared and their biological evaluation in vitro and in vivo have been described. The structures of these compounds were confirmed by ^...A new series compounds, α-methylene-β-carboxy-γ-thiobutyrolactones, have been prepared and their biological evaluation in vitro and in vivo have been described. The structures of these compounds were confirmed by ^1H NMR and FAB-MS spectra.展开更多
Production of b-ketoacyl-Co A, which is catalyzed by 3-ketoacyl-CoA synthase(KCS), is the first step in very long chain fatty acid(VLCFA) biosynthesis. Here we identified 58 KCS genes from Gossypium hirsutum, 31 f...Production of b-ketoacyl-Co A, which is catalyzed by 3-ketoacyl-CoA synthase(KCS), is the first step in very long chain fatty acid(VLCFA) biosynthesis. Here we identified 58 KCS genes from Gossypium hirsutum, 31 from G. arboreum and 33 from G. raimondii by searching the assembled cotton genomes. The gene family was divided into the plant-specific FAE1-type and the more general ELO-type. KCS transcripts were widely expressed and 32 of them showed distinct subgenome-specific expressions in one or more cotton tissues/organs studied. Six Gh KCS genes rescued the lethality of elo2Δelo3Δ yeast double mutant,indicating that this gene family possesses diversified functions.Most KCS genes with GA-responsive elements(GAREs) in the promoters were significantly upregulated by gibberellin A_3(GA).Exogenous GA_3 not only promoted fiber length, but also increased the thickness of cell walls significantly. GAREs present also in the promoters of several cellulose synthase(CesA) genes required for cell wall biosynthesis and they were all induced significantly by GA_3. Because GA treatment resulted in longer cotton fibers with thicker cell walls and higher dry weight per unit cell length, we suggest that it may regulate fiber elongation upstream of the VLCFA-ethylene pathway and also in the downstream steps towards cell wall synthesis.展开更多
基金This work was supported by grants from the National Natural Science Foundation of China(Grant Nos.81572588,81872147)Shantou University Medical College Clinical Trial Uplift Program(Grant No.201423)+4 种基金the Medical Scientific Research Foundation of Guangdong Province,China(Grant No.B2018222)the Traditional Chinese Medicine Research Project from Traditional Chinese Medicine Bureau of Guangdong Province(Grant No.20191182)the Youth Research Grant from Shantou University Medical College Cancer Hospital(Grant No.2018A001,2018A008)the key Project of Science and Technology of Shantou[Grant No.(2018)37]and the Natural Science Foundation of Guangdong Province of China(Grant No.2020A1515010094).
文摘Objective:Our aim was to test the hypothesis that fatty acid synthase(FASN)expression contributes to radioresistance of nasopharyngeal carcinoma(NPC)cells and that inhibiting FASN enhances radiosensitivity.Methods:Targeting FASN using epigallocatechin gallate(EGCG)or RNA interference in NPC cell lines that overexpress endogenous FASN was performed to determine their effects on cellular response to radiationin vitro using MTT and colony formation assays,andin vivo using xenograft animal models.Western blot,immunohistochemistry,real-time PCR arrays,and real-time RT-PCR were used to determine the relationship between FASN and frizzled class receptor 10(FZD10)expression.FZD10 knockdown and overexpression were used to determine its role in mediating FASN function in cellular response to radiation.Immunohistochemical staining was used to determine FASN and FZD10 expressions in human NPC tissues,followed by analysis of their association with the overall survival of patients.Results:FASN knockdown or inhibition significantly enhanced radiosensitivity of NPC cells,bothin vitro andin vivo.There was a positive association between FASN and FZD10 expression in NPC cell lines grown as monolayers or xenografts,as well as human tissues.FASN knockdown reduced FZD10 expression,and rescue of FZD10 expression abolished FASN knockdown-induced enhancement of radiosensitivity.FASN and FZD10 were both negatively associated with overall survival of NPC patients.Conclusions:FASN contributes to radioresistance,possiblyvia FZD10 in NPC cells.Both FZD10 and FASN expressions were associated with poor outcomes of NPC patients.EGCG may sensitize radioresistance by inhibiting FASN and may possibly be developed as a radiosensitizer for better treatment of NPCs.
文摘Background: The liver is the corner stone in lipid metabolism, free fatty acid uptake, synthesizing, storing and exporting lipids;non-alcoholic fatty liver disease (NAFLD) develops if there is any interruption or derangements in lipid metabolim. Fatty acid synthase (FAS) is the major enzyme in lipogenesis, and its circulating level is a bi-omarker of metabolically demanding human diseases. Aim of the Work: To evaluate the level of circulating FAS in NAFLD patients and to correlate it to serum lipid pa-rameters. Materials and Methods: The study included forty NAFLD patients and forty age and sex-matched healthy subjects as controls. Results: FAS levels were signifi-cantly higher in NAFLD patients compared to their level in the controls (P < 0.05). Ad-ditionally, a positive correlation was found between the levels of FAS and BMI (r = 0.57), and between FAS levels and triglycerides and low density lipoprotein cholesterol levels in NAFLD patients (r = 0.79 & 0.53, respectively). Conclusion: Elevated levels of circulating FAS can be considered as a biomarker of fatty liver disease.
基金the Jiangsu Agriculture Science and Technology Innovation Fund(grant no.CX(20)1004)the Earmarked Fund for China Agriculture Research System(grant no.CARS-01).
文摘Fatty acid synthase (FAS) is a multifunctional enzyme that plays an important role in the formation of fatty acids. The fatty acids take part in many processes, such as cell signaling and energy metabolism, and in insects they are important in both cuticular hydrocarbon (CHC) formation and reproduction. Here we characterized the sequence structure and function of an FAS from the small brown planthopper (SBPH), Laodelphax striatellus. The full-length open reading frame (ORF) sequence of LsFAS1 was 7122 bp, encoding a predicted protein of 2373 amino acid residues. There were 7 functional domains in the LsFAS1 protein sequence. Gene expression screening by real-time quantitative polymerase chain reaction (RT-qPCR) showed that LsFAS1 was expressed in all developmental stages. Relative expression was highest at the 4th-instar and female adult stages. Among different tissues, the expression level of LsFAS1 in the ovary was the highest. Phylogenetic analysis showed that LsFAS1 clustered in a clade with 2 FASs from Nilaparvata lugens. Furthermore, these 3 FASs are related to cockroach BgFAS and locust LmFAS. After RNA interference-mediated knock-down, most treated insects died at eclosion. In addition, the lifespan of dsFAS1-treated female adults was shorter than that of the dsGFP-injected control, and offspring production decreased. Also, the expression of vitellogenin (Vg) and vitellogenin receptor (VgR) genes decreased. Virgin females dissected at days 2 and 4 post-eclosion showed many matured oocytes in planthoppers treated with dsGFP but not with dsFAS1. These data highlight the importance of LsFAS1 in SBPH, including a role in reproduction.
基金Supported by Capital Health Development Research Project:Assessment of the Efficacy of BIEJIAJIANWAN Pill in Patients with Chronic Hepatitis B Cirrhosis/Fibrosis (CD2018-2-2173)Beijing Municipal Administration of Hospitals Incubating Program:Clinical Observation on the Treatment of Nonalcoholic Fatty Liver Disease by Invigorating the Spleen,Soothing the Liver,Activating Blood Circulation and Resolving Phlegm (PZ2019011)。
文摘OBJECTIVE: To study the mechanism of Dangfei Liganning capsule(当飞利肝宁胶囊) in the treatment of rats with metabolic associated fatty liver disease(MAFLD). METHODS: Totally 48 specific pathogen free SpragueDawley male rats were randomly divided into normal Group, model group, Dangfei Liganning high, moderate, and low-dose groups and Essentiale group which were fed with high fat diet for 8 weeks, and gavage and molding were carried out simultaneously. Dangfei Liganning high, middle and low-dose group were given 0.27, 0.135 and 0.0675 g·kg-1·d-1 respectively by gavage, Essentiale group was given 0.123 g·kg-1·d-1 by gavage, the same amount of distilled water was given by gavage in the normal group and the model group. The rats were weighed at the 0th week, 2nd week, 4th week, 6th week and 8th weekend respectively. The rats were sacrificed at the end of the 8th week. Serum levels of alanine aminotransferase(ALT), alanine aminotransferase(AST),triglyceride(TG), total cholesterol(CHO), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein (LDL-C), total protein(TP), albumin(Alb), globulin(GLB), total bilirubin(TBIL), direct bilirubin(DBIL), tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) were measured. The levels of liver tumor necrosis factor-α(TNF-α), interleukin-6(IL-6) and liver pathology [hematoxylin and eosin(HE) staining, oil red O staining] were detected. The expression levels of liver X receptor α(LXRα), steroid regulatory element binding protein-1(SREBP-1) and fatty acid synthase(FAS) were detected by immunohistochemistry, Western blot and reverse transcription-polymerase chain reaction reverse transcription-polymerase chain reaction. RESULTS: From the beginning to the 8th week, the growth rate of body weight in the Dangfei Liganning highdose group was slower than all other groups. There was no significant difference in ALB level in all groups(P > 0.05). Compared with the model group, the levels of ALT, AST, LDL-C, TG, CHO, TP, GLB, TBIL, DBIL, IL-6, TNF-α were significantly decreased and HDL-C were significantly increased in Dangfei Liganning high-dose group(P < 0.01, < 0.05). HE and oil red O staining showed that the fatty lesions in rat liver were alleviated, while the expressions of LXRα, SREBP-1, FAS m RNA and protein were significantly decreased(P < 0.01). CONCLUSIONS: Dangfei Liganning capsule can slow down the increase of body weight of MAFLD rats, reduce the levels of transaminase, Lipid and inflammatory factors in MAFLD rats, promote the synthesis of liver protein and bile metabolism, and improve the liver fatty lesion of MAFLD rats, among which the Dangfei Liganning highdose group is more effective. The mechanism of action may be through blocking LXR-SREBP-1-FAS signal pathway.
基金supported by the Research Funds from US National Institute of Health funds (AI069120, AI158154, and AI149718)the UCLA AIDS Institute and UCLA David Geffen School of Medicine-Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research Award ProgramTumor Immunology Training Grant (T32CA912036A1, USA)
文摘SARS-CoV-2 is an emerging viral pathogen and a major global public health challenge since December of 2019, with limited effective treatments throughout the pandemic.As part of the innate immune response to viral infection, type Ⅰ interferons(IFN-Ⅰ) trigger a signaling cascade that culminates in the activation of hundreds of genes, known as interferon stimulated genes(ISGs), that collectively foster an antiviral state.We report here the identification of a group of type Ⅰ interferon suppressed genes,including fatty acid synthase(FASN), which are involved in lipid metabolism.Overexpression of FASN or the addition of its downstream product, palmitate, increased viral infection while knockout or knockdown of FASN reduced infection.More importantly, pharmacological inhibitors of FASN effectively blocked infections with a broad range of viruses, including SARS-CoV-2 and its variants of concern.Thus, our studies not only suggest that downregulation of metabolic genes may present an antiviral strategy by type Ⅰ interferon, but they also introduce the potential for FASN inhibitors to have a therapeutic application in combating emerging infectious diseases such as COVID-19.
文摘Background Estrogen deficiency contributes to postmenopausal osteoporosis. Periosteum might be a potential target of estrogen, but the underlying mechanism at gene level is far from being elucidated. The objective of this study was to investigate the correlation between estrogen and fatty acid synthase (FAS) expression in periosteum. Methods Human periosteum cells were cultured in vitro. Expressed genes in the substrated cDNA library were verified using semi-quantitative PCR and real-time PCR. The expression of FAS in periosteum of ovarectomized (OVX) SD rats was investigated. Results FAS gene was most significantly expressed in the subtracted cDNA library of periosteal cells screened by semi-quantitative PCR. Low FAS expression was verified by real-time PCR in the estrogen exposed human periosteum rather than in the control. The estradiol levels were (20.81±12.62) pg/ml, (19.64±4.35) pg/ml and (13.47±1.84) pg/ml in the sham group, the control, and the OVX group, respectively. The estradiol levels in the OVX group was significantly lower (P=-0.0386). The FAS gene expression in periosteum in the OVX group, sham group, and control group was 3.09±1.97, 1.33±0.47 and 1.51±1.32, respectively. The gene expression in the OVX group was significantly higher (P=0.0372). Conclusion Estrogen modulates FAS gene expression in in vitro human perisoteum as well as in in vivo rat periosteum.
基金Supported by the Financial Support of the Overseas Training Program for Outstanding Young and Middle-Aged Teachers in Universities in Jiangsu Province,China(to Yang FC).
文摘Dietary macronutrients and micronutrients play important roles in human health.On the other hand,the excessive energy derived from food is stored in the form of triacylglycerol.A variety of dietary and hormonal factors affect this process through the regulation of the activities and expression levels of those key player enzymes involved in fatty acid biosynthesis such as acetyl-CoA carboxylase,fatty acid synthase,fatty acid elongases,and desaturases.As a micronutrient,vitamin A is essential for the health of humans.Recently,vitamin A has been shown to play a role in the regulation of glucose and lipid metabolism.This review summarizes recent research progresses about the roles of vitamin A in fatty acid synthesis.It focuses on the effects of vitamin A on the activities and expression levels of mRNA and proteins of key enzymes for fatty acid synthesis in vitro and in vivo.It appears that vitamin A status and its signaling pathway regulate the expression levels of enzymes involved in fatty acid synthesis.Future research directions are also discussed.
文摘The effects and the mechanism of insulin treatment on intracellular lipid metabolism in liver of diabetic rats were evaluated. Type 2 diabetic rats were induced by injecting the streptozotocin (25 mg/kg) and fat rich food. According to the results of oral glucose tolerance test (OGTT) and glucose-induced insulin secretion test (IRT), the rats were divided into two groups: untreated group (UT) and insulin-treated group (IT). Normal rats (NC) served as controls. The treatment with either Humulin N (4-6 U/kg every day), or saline lasted for 4 weeks. Body weight, OGTT, IRT, blood lipids, intracellular lipids in liver, hepatic fatty acid oxidation and the activity of fatty acid synthase (FAS) were detected. The change of liver histology was observed. The insulin sensitivity index (ISI) was applied to assess the status of insulin resistance. The results showed that as compared with NC group, the plasma and hepatic intracellular Triglyceride (TG), total cholesterol (TC) and free fatty acids (FFAs) were increased significantly in UT group (P〈0.05), and lipid droplets could be seen dispersedly in the liver specimens, the hepatic fatty acid oxidation was increased markedly (P〈0.05), while the fatty acid synthase activity decreased (P〈0.05). Insulin treatment resulted in a further accumulation of lipids in liver by 55.7 %, 19.87 % and 22.2 % increase in TG, TC, FFAs respectively. The size of hepatocytes was enlarged and the cells were filled with fat drops. Plasma lipids showed little decrease and still significantly higher than those in NC group after the insulin treatment. Meanwhile, insulin treatment was companied by 20 % decrease in the rate of fatty acid oxidation and 31 % increase in hepatic FAS activity compared to, UT group. It was concluded that treatment with insulin on type 2 diabetic rat increases hepatic intracellular lipid accumulation by inhibiting hepatic fatty acid oxidation and activating FAS.
基金This work was supported by the National Natural Science Foundation of China(Grant No.31772533).
文摘Water retention is critical for physiological homeostasis and survival in terrestrial insects. While deposition of hydrocarbons on insect cuticles as a key measure for water conservation has been extensively investigated, we know little about other mechanisms for preventing water loss in insects. Here, we report two fatty acid synthetic genes that are independent of hydrocarbon production but crucial for water retention in the German cockroach Blattella germanica (L.). First, an integument enriched fatty acid elongase gene (BgElo1) was identified as a critical gene for desiccation resistance in B. germanica;however, knockdown of BgElo1 surprisingly failed to cause a decline in cuticular lipids. In addition, RNA interference (RNAi)-knockdown of an upstream fatty acid synthase gene (BgFas3) showed a similar phenotype, and transmission electron microscopy analysis revealed that BgFas3- or BgElo1-RNAi did not affect cuticle architecture. Bodyweight loss test showed that repression of BgFas3 and BgElo1 significantly increased the weight loss rate, but the difference disappeared when the respiration was closed by freeze killing the cockroaches. A water immersion test was performed, and we found that BgFas3- and BgElo1-RNAi made it difficult for cockroaches to recover from drowning, which was supported by the upregulation of hypoxia-related genes after a 10-h recovery from drowning. Moreover, a dyeing assay with water-soluble Eosin Y showed that this was caused by the entry of water into the respiratory system. Our research suggests that BgFas3 and BgElo1 are required for both inward and outward waterproofing of the respiratory system. This study benefits the understanding of water retention mechanisms in insects.
基金supported by the National Natural Science Foundation of China(Grant Nos.31802035,31872324 and 31601915)the China Postdoctoral Science Foundation(Grant Nos.2017M621841 and 2019T120472).
文摘Goat milk is widely recognized for its nutritional value.Fatty acid synthase(FAS)is the crucial enzyme of fatty acid de novo synthesis.It plays an important role in the formation of goat milk fat.In this paper,we first introduced the molecular regulation process of goat milk fat metabolism based on the structure research of FAS.Secondly,we reviewed some key factors in FAS transcription and post-transcriptional regulation of the goat mammary gland and preliminarily constructed the expression network of the goat mammary gland FAS gene.The purpose of this paper is to systematically introduce the role of FAS in goat milk fat metabolism and to provide a reference for future studies on the mechanism of goat milk fat metabolism.
基金supported by the National High Technology Research and Development Program of China(863 project:2003AA235010)the National Basic Research Program of China(973 project:2004CB518908).
文摘A new series compounds, α-methylene-β-carboxy-γ-thiobutyrolactones, have been prepared and their biological evaluation in vitro and in vivo have been described. The structures of these compounds were confirmed by ^1H NMR and FAB-MS spectra.
基金supported by grants from the China National Basic Research Program (2010CB126000)the National Natural Science Foundation of China (90717009)
文摘Production of b-ketoacyl-Co A, which is catalyzed by 3-ketoacyl-CoA synthase(KCS), is the first step in very long chain fatty acid(VLCFA) biosynthesis. Here we identified 58 KCS genes from Gossypium hirsutum, 31 from G. arboreum and 33 from G. raimondii by searching the assembled cotton genomes. The gene family was divided into the plant-specific FAE1-type and the more general ELO-type. KCS transcripts were widely expressed and 32 of them showed distinct subgenome-specific expressions in one or more cotton tissues/organs studied. Six Gh KCS genes rescued the lethality of elo2Δelo3Δ yeast double mutant,indicating that this gene family possesses diversified functions.Most KCS genes with GA-responsive elements(GAREs) in the promoters were significantly upregulated by gibberellin A_3(GA).Exogenous GA_3 not only promoted fiber length, but also increased the thickness of cell walls significantly. GAREs present also in the promoters of several cellulose synthase(CesA) genes required for cell wall biosynthesis and they were all induced significantly by GA_3. Because GA treatment resulted in longer cotton fibers with thicker cell walls and higher dry weight per unit cell length, we suggest that it may regulate fiber elongation upstream of the VLCFA-ethylene pathway and also in the downstream steps towards cell wall synthesis.