Acetyl-CoA carboxylase inhibitors in non-alcoholic steatohepatitis: Is there a benefit?

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.

Cloning, Expression and Purification of Wheat Acetyl-CoA Carboxylases CT Domain in E. coil

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.

Detection of Acetyl-CoA Carboxylase （ACCase） Inhibitor Herbicides Resistance in Sterile Wild Oat （Avena sterilis L.） Using Agar Quick Test

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.

Acetyl coenzyme A carboxylase modulates lipogenesis and sugar homeostasis in Blattella germanica

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.

The Ca^(2+)/CaN/ACC and cAMP/PKA/HK signal pathways are required for PBAN-mediated sex pheromone biosynthesis in Conogethes punctiferalis

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.

Roles of vitamin A in the regulation of fatty acid synthesis

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.

异质型乙酰辅酶A羧化酶及其生产3-羟基丙酸的研究进展

乙酰辅酶A羧化酶(ACCase)催化底物乙酰辅酶A的羧化,是脂肪酸从头合成的起始限速酶.近年来,在一些嗜热古细菌、丝状不产氧光合细菌等中发现的ACCase还参与一种新型固定二氧化碳的3-羟基丙酸循环代谢途径.ACCase与丙二酰辅酶A还原酶直接催化该循环的起始两步反应,合成代谢特征中间物3-羟基丙酸(3-HP).本文围绕参与脂肪酸从头合成和3-羟基丙酸循环的异质型ACCase,系统介绍和总结异质型ACCase组成差异、催化过程、亚基构象变化和表达调控特点,扩展对ACCase结构与功能多样性和分子进化的理解.同时描述了利用异质型ACCase工程改造合成3-HP,为绿色、高效生物合成3-HP提供理论依据和重要策略.