De novo lipogenesis(DNL)plays an important role in the pathogenesis of hepatic steatosis and also appears to be implicated in hepatic inflammation and fibrosis.Accordingly,the inhibition of acetyl-CoA carboxylase,whic...De novo lipogenesis(DNL)plays an important role in the pathogenesis of hepatic steatosis and also appears to be implicated in hepatic inflammation and fibrosis.Accordingly,the inhibition of acetyl-CoA carboxylase,which catalyzes the ratelimiting step of DNL,might represent a useful approach in the management of patients with nonalcoholic fatty liver disease(NAFLD).Animal studies and preliminary data in patients with NAFLD consistently showed an improvement in steatosis with the use of these agents.However,effects on fibrosis were variable and an increase in plasma triglyceride levels was observed.Therefore,more longterm studies are needed to clarify the role of these agents in NAFLD and to determine their risk/benefit profile.展开更多
This study was conducted using seeds in Petri dish containing agar medium in order to determine acetyl-CoA carboxylase （ACCase） herbicides resistance （R） in Avena sterilis that was grown in wheat fields at Adana p...This study was conducted using seeds in Petri dish containing agar medium in order to determine acetyl-CoA carboxylase （ACCase） herbicides resistance （R） in Avena sterilis that was grown in wheat fields at Adana province, Turkey. Seeds were collected from one large suspected field, where clodinafop-propargyl （Aryloxyphenoxypropionate “FOPs”） and pinoxaden （Phenylpyrazoline “DEN”） have been applied for many years. Susceptible （S） population was collected from the road side on the same region. Agar media of concentration 14 g/L was prepared and it was melted in microwave. Then the amount of 20 mL agar media was added into each Petri dish. Five seeds were placed on agar mediums containing discriminating dose of clodinafop and pinoxaden. Petri dishes were placed in growth incubator operating at 10 °C. After 15 d, both radicle and hypocotyl length were measured. The percentage of germinated seed and dose-response curves were determined. At these different concentration levels, there were more than 50% of R and less than 40% of S seed germinated for pinoxaden. However, for clodinafop, more than 60% of R and less than 50% of S seeds were germinated. At higher concentration levels, the populations of resistant and susceptible were not germinated for both herbicides. The resistance value of R population was then compared with that of the S biotype. From the resistance index （RI）, the population was more resistant to pinoxaden （7.43 for radicle and 2.47 for hypocotyl） than the clodinafop-propagyl （1.39 for radicle and 3.77 for hypocotyl）. The method provided a simple, quick and cost effective way to identify ACCase herbicides resistance in most grass weeds.展开更多
The entire gene of carboxyltransferase（CT） domain of acetyl-CoA carboxylase（ACCase） from Chinese Spring wheat（CSW） plastid was cloned firstly, and the 2.3 kb gene was inserted into PET28a^＋ vector and expressed...The entire gene of carboxyltransferase（CT） domain of acetyl-CoA carboxylase（ACCase） from Chinese Spring wheat（CSW） plastid was cloned firstly, and the 2.3 kb gene was inserted into PET28a^＋ vector and expressed in E. coil in a soluble state. The （His）6 fusion protein was identified by SDS-PAGE and Western blot. The recombinant protein was purified by affinity chromatography, and the calculated molecular mass（Mr） was 88000. The results of the sequence analysis indicate that the cloned gene（GeneBank accession No. EU124675） was a supplement and revision of the reported ACCase CT partial cDNA from Chinese Spring wheat plastid. The recombinant protein will be significant for us to investigate the recognizing mechanism between ACCase and herbicides, and further to screen new herbicides.展开更多
Lipid and sugar homeostasis is critical for insect development and survival.In this study,we characterized an acetyl coenzyme A carboxylase gene in Blattella germanica(BgACC)that is involved in both lipogenesis and su...Lipid and sugar homeostasis is critical for insect development and survival.In this study,we characterized an acetyl coenzyme A carboxylase gene in Blattella germanica(BgACC)that is involved in both lipogenesis and sugar homeostasis.We found that BgACC was dominantly expressed in the fat body and integument,and was significantly upregulated after molting.Knockdown of BgACC in 5th-instar nymphs did not affect their normal molting to the next nymphal stage,but it caused a lethal phenotype during adult emergence.BgACC-RNA interference(RNAi)significantly downregulated total free fatty acid(FFA)and triacylglycerol(TAG)levels,and also caused a significant decrease of cuticular hydrocarbons(CHCs).Repression of BgACC in adult females affected the development of oocytes and resulted in sterile females,but BgACC-RNAi did not affect the reproductive ability of males.Interestingly,knockdown of BgACC also changed the expression of insulin-like peptide genes(BglLPs),which mimicked a physiological state of high sugar uptake.In addition,BgACC was upregulated when B.germanica were fed on a high sucrose diet,and repression of BgACC upregulated the expression of the glycogen synthase gene(BgGlyS).Moreover,BgACC-RNAi increased the circulating sugar levels and glycogen storage,and a longevity assay suggested that BgACC was important for the survival of B.germanica under conditions of high sucrose uptake.Our results confirm that BgACC is involved in multiple lipid biogenesis and sugar homeostasis processes,which further modulates insect reproduction and sugar tolerance.This study benefits our understanding of the crosstalk between lipid and sugar metabolism.展开更多
Conogethes punctiferalis is a crop and fruit pest that has caused serious economic losses to agricultural production.This pest relies heavily on its sex pheromone to ensure sexual encounters and subsequent mating succ...Conogethes punctiferalis is a crop and fruit pest that has caused serious economic losses to agricultural production.This pest relies heavily on its sex pheromone to ensure sexual encounters and subsequent mating success.However,the molecular mechanism underlying sex pheromone biosynthesis in this species remains elusive.The present study investigated the detailed mechanism underlying PBAN-regulated sex pheromone biosynthesis in C.punctiferalis by transcriptome sequencing of the C.punctiferalis pheromone glands(PGs)and subsequent functional identification of the target genes.The results showed that female mating started from the first scotophase,and peaked at the second to fifth scotophases in accordance with the release of sex pheromones.PBAN regulated sex pheromone biosynthesis by employing Ca^(2+)and cAMP as secondary messengers,as demonstrated by RNA interference(RNAi),pharmacological inhibitors,and behavioral assays.Further investigation revealed that calcineurin(CaN)and acetyl-CoA carboxylase(ACC)were activated by PBAN/Ca^(2+)signaling,and the RNAimediated knockdown of CaN and ACC transcripts significantly reduced sex pheromone production,ultimately leading to a significantly reduced ability of females to attract males.Importantly,hexokinase(HK)was found to regulate sex pheromone biosynthesis in response to the PBAN/cAMP/PKA signaling pathway,as demonstrated by RNAi,enzyme activity,and pharmacological inhibitor assays.Furthermore,Far2 and Desaturase1 were found to participate in PBAN-regulated sex pheromone biosynthesis.Altogether,our findings revealed that PBAN regulates sex pheromone biosynthesis through the PBANR/Ca^(2+)/CaN/ACC and PBANR/cAMP/PKA/HK pathways in C.punctiferalis,which enriches our comprehension of the details of sex pheromone biosynthesis in moths.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
ATP citrate lyase(ACLY)synthesizes cytosolic acetyl coenzyme A(acetyl-CoA),an essential biosynthetic precursor for lipid synthesis and the acetyl donor required for protein acetylation.The aberrant expression and acti...ATP citrate lyase(ACLY)synthesizes cytosolic acetyl coenzyme A(acetyl-CoA),an essential biosynthetic precursor for lipid synthesis and the acetyl donor required for protein acetylation.The aberrant expression and activity of ACLY has been documented in multiple human cancers.ETC-1002 is an indirect ACLY inhibitor,and it has recently been approved by the FDA as an additional therapeutic option in high-risk hypercholesterolemia patients unable to meet goals with standard therapy.In this work,we identified a series of novel long-chain alkenyl diacids as potent direct ACLY inhibitors,and comprehensive structure-activity relationship analysis showed that compound 18f was the most potent ACLY inhibitor with an IC50 value of 1.5μmol/L.Subsequent ester formation of 18f gave a new series of compounds such as 25f that maintained ACLY inhibitory activity and improved antitumor cell proliferation effects.展开更多
文摘De novo lipogenesis(DNL)plays an important role in the pathogenesis of hepatic steatosis and also appears to be implicated in hepatic inflammation and fibrosis.Accordingly,the inhibition of acetyl-CoA carboxylase,which catalyzes the ratelimiting step of DNL,might represent a useful approach in the management of patients with nonalcoholic fatty liver disease(NAFLD).Animal studies and preliminary data in patients with NAFLD consistently showed an improvement in steatosis with the use of these agents.However,effects on fibrosis were variable and an increase in plasma triglyceride levels was observed.Therefore,more longterm studies are needed to clarify the role of these agents in NAFLD and to determine their risk/benefit profile.
文摘This study was conducted using seeds in Petri dish containing agar medium in order to determine acetyl-CoA carboxylase （ACCase） herbicides resistance （R） in Avena sterilis that was grown in wheat fields at Adana province, Turkey. Seeds were collected from one large suspected field, where clodinafop-propargyl （Aryloxyphenoxypropionate “FOPs”） and pinoxaden （Phenylpyrazoline “DEN”） have been applied for many years. Susceptible （S） population was collected from the road side on the same region. Agar media of concentration 14 g/L was prepared and it was melted in microwave. Then the amount of 20 mL agar media was added into each Petri dish. Five seeds were placed on agar mediums containing discriminating dose of clodinafop and pinoxaden. Petri dishes were placed in growth incubator operating at 10 °C. After 15 d, both radicle and hypocotyl length were measured. The percentage of germinated seed and dose-response curves were determined. At these different concentration levels, there were more than 50% of R and less than 40% of S seed germinated for pinoxaden. However, for clodinafop, more than 60% of R and less than 50% of S seeds were germinated. At higher concentration levels, the populations of resistant and susceptible were not germinated for both herbicides. The resistance value of R population was then compared with that of the S biotype. From the resistance index （RI）, the population was more resistant to pinoxaden （7.43 for radicle and 2.47 for hypocotyl） than the clodinafop-propagyl （1.39 for radicle and 3.77 for hypocotyl）. The method provided a simple, quick and cost effective way to identify ACCase herbicides resistance in most grass weeds.
基金Supported by the National Natural Science Foundation of China(Nos. 20432010, 20672045 and 30570405)
文摘The entire gene of carboxyltransferase（CT） domain of acetyl-CoA carboxylase（ACCase） from Chinese Spring wheat（CSW） plastid was cloned firstly, and the 2.3 kb gene was inserted into PET28a^＋ vector and expressed in E. coil in a soluble state. The （His）6 fusion protein was identified by SDS-PAGE and Western blot. The recombinant protein was purified by affinity chromatography, and the calculated molecular mass（Mr） was 88000. The results of the sequence analysis indicate that the cloned gene（GeneBank accession No. EU124675） was a supplement and revision of the reported ACCase CT partial cDNA from Chinese Spring wheat plastid. The recombinant protein will be significant for us to investigate the recognizing mechanism between ACCase and herbicides, and further to screen new herbicides.
基金funded by the National Natural Science Foundation of China(32200384)the China Postdoctoral Science Foundation(2022M710053).
文摘Lipid and sugar homeostasis is critical for insect development and survival.In this study,we characterized an acetyl coenzyme A carboxylase gene in Blattella germanica(BgACC)that is involved in both lipogenesis and sugar homeostasis.We found that BgACC was dominantly expressed in the fat body and integument,and was significantly upregulated after molting.Knockdown of BgACC in 5th-instar nymphs did not affect their normal molting to the next nymphal stage,but it caused a lethal phenotype during adult emergence.BgACC-RNA interference(RNAi)significantly downregulated total free fatty acid(FFA)and triacylglycerol(TAG)levels,and also caused a significant decrease of cuticular hydrocarbons(CHCs).Repression of BgACC in adult females affected the development of oocytes and resulted in sterile females,but BgACC-RNAi did not affect the reproductive ability of males.Interestingly,knockdown of BgACC also changed the expression of insulin-like peptide genes(BglLPs),which mimicked a physiological state of high sugar uptake.In addition,BgACC was upregulated when B.germanica were fed on a high sucrose diet,and repression of BgACC upregulated the expression of the glycogen synthase gene(BgGlyS).Moreover,BgACC-RNAi increased the circulating sugar levels and glycogen storage,and a longevity assay suggested that BgACC was important for the survival of B.germanica under conditions of high sucrose uptake.Our results confirm that BgACC is involved in multiple lipid biogenesis and sugar homeostasis processes,which further modulates insect reproduction and sugar tolerance.This study benefits our understanding of the crosstalk between lipid and sugar metabolism.
基金supported by the National Natural Science Foundation of China(31970472,32272547)the National Science Fund of Henan Province for Distinguished Young Scholars,China(202300410191)+3 种基金the Basic Research Project of the Key Scientific Research Projects of Universities in Henan Province,China(21zx013)the Henan Agricultural Research System,China(HARS-2209-G3)the Henan Special Support for High-Level Talents Central Plains Science and Technology Innovation Leading Talents,China(224200510018)the earmarked fund for China Agricultural Research System(CARS-27)。
文摘Conogethes punctiferalis is a crop and fruit pest that has caused serious economic losses to agricultural production.This pest relies heavily on its sex pheromone to ensure sexual encounters and subsequent mating success.However,the molecular mechanism underlying sex pheromone biosynthesis in this species remains elusive.The present study investigated the detailed mechanism underlying PBAN-regulated sex pheromone biosynthesis in C.punctiferalis by transcriptome sequencing of the C.punctiferalis pheromone glands(PGs)and subsequent functional identification of the target genes.The results showed that female mating started from the first scotophase,and peaked at the second to fifth scotophases in accordance with the release of sex pheromones.PBAN regulated sex pheromone biosynthesis by employing Ca^(2+)and cAMP as secondary messengers,as demonstrated by RNA interference(RNAi),pharmacological inhibitors,and behavioral assays.Further investigation revealed that calcineurin(CaN)and acetyl-CoA carboxylase(ACC)were activated by PBAN/Ca^(2+)signaling,and the RNAimediated knockdown of CaN and ACC transcripts significantly reduced sex pheromone production,ultimately leading to a significantly reduced ability of females to attract males.Importantly,hexokinase(HK)was found to regulate sex pheromone biosynthesis in response to the PBAN/cAMP/PKA signaling pathway,as demonstrated by RNAi,enzyme activity,and pharmacological inhibitor assays.Furthermore,Far2 and Desaturase1 were found to participate in PBAN-regulated sex pheromone biosynthesis.Altogether,our findings revealed that PBAN regulates sex pheromone biosynthesis through the PBANR/Ca^(2+)/CaN/ACC and PBANR/cAMP/PKA/HK pathways in C.punctiferalis,which enriches our comprehension of the details of sex pheromone biosynthesis in moths.
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.
基金supported by grants fromthe"Personalized Medicines-Molecular Signature-based Drug Discovery and Development"Strategic Priority Research Program of the Chinese Academy of Sciences(XDA12040328)the Medical Guidance Project of Shanghai ScienceandTechnology Commission(20S11903400)+1 种基金the Natural Science Foundation of Shanghai's 2021"Science and Technology InnovationAction Plan"(21ZR1475300)the National Natural Science Foundation of China(No.82170872).
文摘ATP citrate lyase(ACLY)synthesizes cytosolic acetyl coenzyme A(acetyl-CoA),an essential biosynthetic precursor for lipid synthesis and the acetyl donor required for protein acetylation.The aberrant expression and activity of ACLY has been documented in multiple human cancers.ETC-1002 is an indirect ACLY inhibitor,and it has recently been approved by the FDA as an additional therapeutic option in high-risk hypercholesterolemia patients unable to meet goals with standard therapy.In this work,we identified a series of novel long-chain alkenyl diacids as potent direct ACLY inhibitors,and comprehensive structure-activity relationship analysis showed that compound 18f was the most potent ACLY inhibitor with an IC50 value of 1.5μmol/L.Subsequent ester formation of 18f gave a new series of compounds such as 25f that maintained ACLY inhibitory activity and improved antitumor cell proliferation effects.
