Regulation Of Fatty Acid Synthesis Research Articles

Knocking out the carboxyltransferase interactor 1 (CTI1) in Chlamydomonas boosted oil content by fivefold without affecting cell growth.

The first step in chloroplast de novo fatty acid synthesis is catalysed by acetyl-CoA carboxylase (ACCase). As the rate-limiting step for this pathway, ACCase is subject to both positive and negative regulation. In this study, we identify a Chlamydomonas homologue of the plant carboxyltransferase interactor 1 (CrCTI1) and show that this protein interacts with the Chlamydomonas α-carboxyltransferase (Crα-CT) subunit of the ACCase by yeast two-hybrid protein-protein interaction assay. Three independent CRISPR-Cas9 mediated knockout mutants for CrCTI1 each produced an 'enhanced oil' phenotype, accumulating 25% more total fatty acids and storing up to fivefold more triacylglycerols (TAGs) in lipid droplets. The TAG phenotype of the crcti1 mutants was not influenced by light but was affected by trophic growth conditions. By growing cells under heterotrophic conditions, we observed a crucial function of CrCTI1 in balancing lipid accumulation and cell growth. Mutating a previously mapped in vivo phosphorylation site (CrCTI1 Ser108 to either Ala or to Asp), did not affect the interaction with Crα-CT. However, mutating all six predicted phosphorylation sites within Crα-CT to create a phosphomimetic mutant reduced this pairwise interaction significantly. Comparative proteomic analyses of the crcti1 mutants and WT suggested a role for CrCTI1 in regulating carbon flux by coordinating carbon metabolism, antioxidant and fatty acid β-oxidation pathways, to enable cells to adapt to carbon availability. Taken together, this study identifies CrCTI1 as a negative regulator of fatty acid synthesis in algae and provides a new molecular brick for the genetic engineering of microalgae for biotechnology purposes.

Comprehensive Analysis of CaFAD Genes Involved in Fatty Acid Accumulation in Coffea arabica and Functional Characterization of CaFAD8 in Transgenic Arabidopsis thaliana

The quality of Coffee arabica L. beans, particularly the aroma, is a key determinant of commercial value. Fatty acids, as precursors of volatile aroma compounds, play a crucial role in this quality. Screening and identification of their related genes are of particular significance. This study identified 21 members of the CaFAD gene family in the C. arabica genome using bioinformatics tools. Gene duplication events observed in the CaFAD gene family were likely driven by natural selection and mutation pressure, with natural selection being more prominent. Transcriptome sequencing, qRT-PCR, and fatty acid profiling across four fruit developmental stages revealed that CaFAD8 was closely associated with fatty acid synthesis regulation. Fatty acid content was initially high but decreased during the later stages, while CaFAD8 expression showed an inverse pattern. Subcellular localization indicated that CaFAD8 functions primarily on the inner membrane. CaFAD8-OE heterologous expression experiment in Arabidopsis thaliana reduced the total fatty acid content in seeds but increased unsaturated fatty acids, including oleic, linoleic, and linolenic acids. These findings suggest that CaFAD8 promotes fatty acid unsaturation and provides insights into fatty acid metabolism in C. arabica. This study offers a foundation for understanding CaFAD gene regulation and supports breeding strategies for high-oil C. arabica varieties.

OsLAP3/OsSTRL2, encoding a rice strictosidine synthase, is required for anther cuticle formation and pollen exine patterning in rice.

The formation of the anther wall and the development of pollen processes, central to rice fertility and yield, are highly dependent on the synthesis and accumulation of lipid polymers. Although several regulatory factors related to lipid biosynthesis during pollen wall development have been identified, the molecular mechanisms controlling these processes remain poorly understood. In this study, a male-sterile rice mutant, lap3, was identified, characterized by normal vegetative growth but complete male sterility due to delayed programmed cell death (PCD) in tapetal cells and defects in anther cuticle and pollen exine formation. Map-based cloning revealed that OsLAP3 is a new allele of the strictosidine synthase-like gene, OsSTRL2. Functional analysis, including complementation and CRISPR/Cas9-based gene editing, confirmed that the 2-nucleotide deletion in the OsLAP3 is responsible for the male sterility phenotype. OsLAP3 is homologous to the maize ZmMS45, the core recessive nuclear sterile gene of maize Seed Production Technology (SPT), and localizes to the endoplasmic reticulum and plays a conserved role in anther development and pollenformation. Gene expression analysis revealed a significant downregulation of key genes involved in anther development and sporopollenin biosynthesis in lap3 anthers. Furthermore, lipid profiling demonstrated a marked reduction in both wax and cutin content. These findings establish OsLAP3 as a critical regulator of fatty acid synthesis and highlight its role in anther cuticle formation and pollen exine development. The findings of this study provide valuable insights into the molecular regulation of lipid biosynthesis during rice male reproductive development and offer potential applications for hybrid rice breeding.

Distinct roles of avocado transcription factors PaRAP2.4-2 and PaERF082-1 in fatty acid synthesis regulation in transgenic Arabidopsis thaliana

Distinct roles of avocado transcription factors PaRAP2.4-2 and PaERF082-1 in fatty acid synthesis regulation in transgenic Arabidopsis thaliana

REGULATOR OF FATTY ACID SYNTHESIS proteins regulate de novo fatty acid synthesis by modulating hetACCase distribution.

In plants, heteromeric acetyl-CoA carboxylase (hetACCase) initiates de novo fatty acid synthesis (FAS) by generating malonyl-CoA in the first committed step of this process. hetACCase activity is precisely regulated to meet the cellular demand for acyl chains during the plant life cycle. In this study, we performed a systematic coexpression analysis of hetACCase and its regulators in Arabidopsis (Arabidopsis thaliana) to better understand the regulatory mechanism of hetACCase. Our analysis uncovered REGULATOR OF FATTY ACID SYNTHESIS 1 (RFS1), whose expression is positively correlated with that of other regulators of hetACCase. The RFS gene family encodes two plastid inner envelope membrane proteins with undiscovered roles. Further analysis revealed that RFS1 colocalizes and directly interacts with CARBOXYLTRANSFERASE INTERACTOR 1 (CTI1). CRISPR/Cas9-mediated knockouts of RFSs exhibit enhanced hetACCase activity, higher FAS rates, and increased fatty acid contents, with particularly marked accumulation of absolute triacylglycerol levels in leaves, similar to cti mutants. The mutations of rfs and cti alter the plastid membrane distribution pattern of α-CT, leading to reduced hetACCase activity on the membrane, which could potentially be the original mechanism through which RFSs restrain hetACCase activity. Thus, we reveal a unique regulatory module that regulates de novo FAS and a genetic locus that may contribute to breeding of improved oil crops.

Selective and brain-penetrant ACSS2 inhibitors target breast cancer brain metastatic cells.

Breast cancer brain metastasis (BCBM) typically results in an end-stage diagnosis and is hindered by a lack of brain-penetrant drugs. Tumors in the brain rely on the conversion of acetate to acetyl-CoA by the enzyme acetyl-CoA synthetase 2 (ACSS2), a key regulator of fatty acid synthesis and protein acetylation. Here, we used a computational pipeline to identify novel brain-penetrant ACSS2 inhibitors combining pharmacophore-based shape screen methodology with absorption, distribution, metabolism, and excretion (ADME) property predictions. We identified compounds AD-5584 and AD-8007 that were validated for specific binding affinity to ACSS2. Treatment of BCBM cells with AD-5584 and AD-8007 leads to a significant reduction in colony formation, lipid storage, acetyl-CoA levels and cell survival in vitro. In an ex vivo brain-tumor slice model, treatment with AD-8007 and AD-5584 reduced pre-formed tumors and synergized with irradiation in blocking BCBM tumor growth. Treatment with AD-8007 reduced tumor burden and extended survival in vivo. This study identifies selective brain-penetrant ACSS2 inhibitors with efficacy towards breast cancer brain metastasis.

Dimethyloxalylglycine Suppresses SREBP1c and Lipogenic Gene Expressions in Hepatocytes Independently of HIF1A.

Dimethyloxalylglycine (DMOG) is a representative inhibitor of the prolyl hydroxylase domain (PHD), which mediates the degradation of hypoxia-inducible factor-1-alpha (HIF1A). DMOG exerts its pharmacological effects via the canonical pathway that involves PHD inhibition; however, it remains unclear whether DMOG affects lipogenic gene expression in hepatocytes. We aimed to elucidate the effects of DMOG on sterol regulatory element-binding protein-1c (SREBP1c), a master regulator of fatty acid synthesis in hepatocytes. DMOG treatment inhibited SREBP1c mRNA and protein expression in HepG2 and AML12 hepatocytes and reduced the transcript levels of SREBP1c-regulated lipogenic genes. A luciferase reporter assay revealed that DMOG inhibited the transcriptional activity of SREBP1c. Moreover, DMOG suppressed SREBP1c expression in mice liver. Mechanistically, treatment with DMOG enhanced the expression of HIF1A and insulin-induced gene 2 (INSIG2), which inhibits the activation of SREBP1c. However, HIF1A or INSIG2 knockdown failed to reverse the inhibitory effect of DMOG on SREBP1c expression, suggesting a redundant role of HIF1A and INSIG2 in terms of repressing SREBP1c. DMOG did not function through the canonical pathway involving inhibition of SREBP1c by PHD, highlighting the presence of non-canonical pathways that mediate its anti-lipogenic effect.

ARMH1 is a novel marker associated with poor pediatric AML outcomes that affect the fatty acid synthesis and cell cycle pathways.

Despite remarkable progress in Pediatric Acute Myeloid Leukemia (pAML) treatments, the relapsed disease remains difficult to treat, making it pertinent to identify novel biomarkers of prognostic/therapeutic significance. Bone marrow samples from 21 pAML patients were analyzed using single cell RNA sequencing, functional assays with ARMH1 knockdown and overexpression were performed in leukemia cell lines to evaluate impact on proliferation and migration, and chemotherapy sensitivity. Mitochondrial function was assessed via Seahorse assay, ARMH1 interacting proteins were studied using co-immunoprecipitation. Bulk RNA-seq was performed on ARMH1knockdown and over expressing cell lines to evaluate the pathways and networks impacted by ARMH1. Our data shows that ARMH1, a novel cancer-associated gene, is highly expressed in the malignant blast cells of multiple pediatric hematologic malignancies, including AML, T/B-ALL, and T/B-MPAL. Notably, ARMH1 expression is significantly elevated in blast cells of patients who relapsed or have a high-risk cytogenetic profile (MLL) compared to standard-risk (RUNX1, inv (16)). ARMH1 expression is also significantly correlated with the pediatric leukemia stem cell score of 6 genes (LSC6) associated with poor outcomes. Perturbation of ARMH1 (knockdown and overexpression) in leukemia cell lines significantly impacted cell proliferation and migration. The RNA-sequencing analysis on multiple ARMH1 knockdown and overexpressing cell lines established an association with mitochondrial fatty acid synthesis and cell cycle pathways.The investigation of the mitochondrial matrix shows that pharmacological inhibition of a key enzyme in fatty acid synthesis regulation, CPT1A, resulted in ARMH1 downregulation. ARMH1 knockdown also led to a significant reduction in CPT1A and ATP production as well as Oxygen Consumption Rate. Our data indicates that downregulating ARMH1 impacts cell proliferation by reducing key cell cycle regulators such as CDCA7 and EZH2. Further, we also established that ARMH1 is a key physical interactant of EZH2, associated with multiple cancers. Our findings underscore further evaluation of ARMH1 as a potential candidate for targeted therapies and stratification of aggressive pAML to improve outcomes.

MBTPS2 acts as a regulator of lipogenesis and cholesterol synthesis through SREBP signalling in prostate cancer

BackgroundProstate cancer is the most common cancer in men in the developed world, with most deaths caused by advanced and metastatic disease which has no curative options. Here, we identified Mbtps2 alteration to be associated with metastatic disease in an unbiased in vivo screen and demonstrated its regulation of fatty acid and cholesterol metabolism.MethodsThe Sleeping Beauty transposon system was used to randomly alter gene expression in the PtenNull murine prostate. MBTPS2 was knocked down by siRNA in LNCaP, DU145 and PC3 cell lines, which were then phenotypically investigated. RNA-Seq was performed on LNCaP cells lacking MBTPS2, and pathways validated by qPCR. Cholesterol metabolism was investigated by Filipin III staining.ResultsMbtps2 was identified in our transposon-mediated in vivo screen to be associated with metastatic prostate cancer. Silencing of MBTPS2 expression in LNCaP, DU145 and PC3 human prostate cancer cells reduced proliferation and colony forming growth in vitro. Knockdown of MBTPS2 expression in LNCaP cells impaired cholesterol synthesis and uptake along with reduced expression of key regulators of fatty acid synthesis, namely FASN and ACACA.ConclusionMBTPS2 is implicated in progressive prostate cancer and may mechanistically involve its effects on fatty acid and cholesterol metabolism.

UCP2-induced fatty acid synthase promotes NLRP3 inflammasome activation during sepsis.

Cellular lipid metabolism has been linked to immune responses; however, the precise mechanisms by which de novo fatty acid synthesis can regulate inflammatory responses remain unclear. The NLRP3 inflammasome serves as a platform for caspase-1–dependent maturation and secretion of proinflammatory cytokines. Here, we demonstrated that the mitochondrial uncoupling protein-2 (UCP2) regulates NLRP3-mediated caspase-1 activation through the stimulation of lipid synthesis in macrophages. UCP2-deficient mice displayed improved survival in a mouse model of polymicrobial sepsis. Moreover, UCP2 expression was increased in human sepsis. Consistently, UCP2-deficient mice displayed impaired lipid synthesis and decreased production of IL-1β and IL-18 in response to LPS challenge. In macrophages, UCP2 deficiency suppressed NLRP3-mediated caspase-1 activation and NLRP3 expression associated with inhibition of lipid synthesis. In UCP2-deficient macrophages, inhibition of lipid synthesis resulted from the downregulation of fatty acid synthase (FASN), a key regulator of fatty acid synthesis. FASN inhibition by shRNA and treatment with the chemical inhibitors C75 and cerulenin suppressed NLRP3-mediated caspase-1 activation and inhibited NLRP3 and pro–IL-1β gene expression in macrophages. In conclusion, our results suggest that UCP2 regulates the NLRP3 inflammasome by inducing the lipid synthesis pathway in macrophages. These results identify UCP2 as a potential therapeutic target in inflammatory diseases such as sepsis.

The acyl-CoA-binding protein 2 exhibited the highest affinity for palmitoyl-CoA and promoted Monascus pigment production

PurposeThe present study aimed to explore the binding ability of acyl-CoA binding protein 2 to fatty acid acyl-CoA esters and its effect on Monascus pigment production in M. ruber CICC41233.MethodsThe Mracbp2 gene from M. ruber CICC41233 was cloned with a total DNA and cDNA as the templates through the polymerase chain reaction. The cDNA of the Mracbp2 gene fragment was ligated to expression vector pGEX-6P-1 to construct pGEX-MrACBP2, which was expressed in Escherichia coli BL21 to obtain the fusion protein GST-MrACBP2 and then measure the binding ability of fatty acid acyl-CoA esters. Additionally, the DNA of the Mracbp2 gene fragment was ligated to expression vector pNeo0380 to construct pNeo0380-MrACBP2, which was homologously over-expressed in M. ruber CICC41233 to evaluate Monascus pigment production and fatty acid.ResultsThe cloned Mracbp2 gene of the DNA and cDNA sequence was 1525 bp and 1329 bp in length, respectively. The microscale thermophoresis binding assay revealed that the purified GST-MrACBP2 had the highest affinity for palmitoyl-CoA (Kd =70.57 nM). Further, the Mracbp2 gene was homologously overexpressed in M. ruber CICC41233, and a positive transformant M. ruber ACBP-E was isolated. In the Monascus pigments fermentation, the expression level of the Mracbp2 gene was increased by 1.74-fold after 2 days and 2.38-fold after 6 days. The palmitic acid content and biomass in M. ruber ACBP2-E were significantly lower than that in M. ruber CICC41233 on 2 days and 6 days. However, compared with M. ruber CICC41233, the yields of total pigment, ethanol-soluble pigment, and water-soluble pigment in M. ruber ACBP2-E increased by 63.61%, 71.61%, and 29.70%, respectively.ConclusionsThe purified fusion protein GST-MrACBP2 exhibited the highest affinity for palmitoyl-CoA. The Mracbp2 gene was overexpressed in M. ruber CICC41233, which resulted in a decrease in palmitic acid and an increase in Monascus pigments. Overall, the effect of MrACBP2 on the synthesis of fatty acid and Monascus pigment was explored. This paper explored the effect of MrACBP2 on the fatty acid synthesis and the synthesis of Monascus pigment. The results indicated the regulation of fatty acid synthesis could affect Monascus pigment synthesis, providing a novel strategy for improving the yield of Monascus pigment.

An expanded role for the transcription factor WRINKLED1 in the biosynthesis of triacylglycerols during seed development.

The transcription factor WRINKLED1 (WRI1) is known as a master regulator of fatty acid synthesis in developing oilseeds of Arabidopsis thaliana and other species. WRI1 is known to directly stimulate the expression of many fatty acid biosynthetic enzymes and a few targets in the lower part of the glycolytic pathway. However, it remains unclear to what extent and how the conversion of sugars into fatty acid biosynthetic precursors is controlled by WRI1. To shortlist possible gene targets for future in-planta experimental validation, here we present a strategy that combines phylogenetic foot printing of cis-regulatory elements with additional layers of evidence. Upstream regions of protein-encoding genes in A. thaliana were searched for the previously described DNA-binding consensus for WRI1, the ASML1/WRI1 (AW)-box. For about 900 genes, AW-box sites were found to be conserved across orthologous upstream regions in 11 related species of the crucifer family. For 145 select potential target genes identified this way, affinity of upstream AW-box sequences to WRI1 was assayed by Microscale Thermophoresis. This allowed definition of a refined WRI1 DNA-binding consensus. We find that known WRI1 gene targets are predictable with good confidence when upstream AW-sites are phylogenetically conserved, specifically binding WRI1 in the in vitro assay, positioned in proximity to the transcriptional start site, and if the gene is co-expressed with WRI1 during seed development. When targets predicted in this way are mapped to central metabolism, a conserved regulatory blueprint emerges that infers concerted control of contiguous pathway sections in glycolysis and fatty acid biosynthesis by WRI1. Several of the newly predicted targets are in the upper glycolysis pathway and the pentose phosphate pathway. Of these, plastidic isoforms of fructokinase (FRK3) and of phosphoglucose isomerase (PGI1) are particularly corroborated by previously reported seed phenotypes of respective null mutations.

Identification and Functional Characterization of Adenosine Deaminase in Mucor circinelloides: A Novel Potential Regulator of Nitrogen Utilization and Lipid Biosynthesis.

Adenosine deaminase (ADA) is an enzyme distributed in a wide variety of organisms that cleaves adenosine into inosine. Since inosine plays an important role in nitrogen metabolism, ADA may have a critical function in the regulation of fatty acid synthesis. However, the role of ADA in oleaginous fungi has not been reported so far. Therefore, in this study, we identified one ada gene encoding ADA (with ID scaffold0027.9) in the high lipid-producing fungus, Mucor circinelloides WJ11, and investigated its role in cell growth, lipid production, and nitrogen metabolism by overexpressing and knockout of this gene. The results showed that knockout of the ada altered the efficiency of nitrogen consumption, which led to a 20% increment in the lipid content (25% of cell dry weight) of the engineered strain, while overexpression of the ada showed no significant differences compared with the control strain at the final growth stage; however, interestingly, it increased lipid accumulation at the early growth stage. Additionally, transcriptional analysis was conducted by RT-qPCR and our findings indicated that the deletion of ada activated the committed steps of lipid biosynthesis involved in acetyl-CoA carboxylase (acc1 gene), cytosolic malic acid enzyme (cme1 gene), and fatty acid synthases (fas1 gene), while it suppressed the expression of AMP-activated protein kinase (ampk α1 and ampk β genes), which plays a role in lipolysis, whereas the ada-overexpressed strain displayed reverse trends. Conclusively, this work unraveled a novel role of ADA in governing lipid biosynthesis and nitrogen metabolism in the oleaginous fungus, M. circinelloides.

Comparative transcriptomic analysis reveals genes related to the rapid accumulation of oleic acid in Camellia chekiangoleosa, an oil tea plant with early maturity and large fruit

Camellia chekiangoleosa has a higher oleic acid content and a shorter reproductive cycle than typical oil tea plants. It was intensively sampled over six C. chekiangoleosa seed development stages. The content of fatty acids determined by GC showed that the accumulation of fatty acids gradually increased from the S1 to S5 stages, and the maximum concentration was reached in S5. Then, fatty acids declined slightly in S6. The main fatty acid component showed the same accumulation trend as the total fatty acids, except linolenic acid, which remained at a low level throughout seed developmental stages. Changes in the expression of fatty acid accumulation-related genes were monitored using second-generation and SMRT full-length transcriptome sequencing. Finally, 18.92 G accurate and reliable data were obtained. Differential expression analysis and weighted coexpression analysis revealed two “gene modules” significantly associated with oleic acid and linoleic acid contents, and the high expression of ENR, KAS I, and KAS II, which accumulate substrates for oleic acid synthesis, was thought to be responsible for the rapid accumulation of fatty acids in the early stage. The rapid increase in fatty acids in the second stage may be closely related to the synergy between the high expression of SAD and low expression of FAD2. In addition, many transcription factors, such as ERF, GRAS, GRF, MADS, MYB and WRKY, may be involved in the fatty acid synthesis. Our data provide a rich resource for further studies on the regulation of fatty acid synthesis in C. chekiangoleosa.

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.

A novel metabolic function of Myc in regulation of fatty acid synthesis in prostate cancer.

A subset of human prostate cancer exhibits increased de novo synthesis of fatty acids, but the molecular driver(s) of this metabolic abnormality remains obscure. This study demonstrates a novel metabolic function of c-Myc (Myc) in regulation of fatty acid synthesis. The role of Myc in regulation of fatty acid synthesis was investigated by: (a) interrogation of the prostate cancer The Cancer Genome Atlas (TCGA) dataset, (b) chromatin immunoprecipitation, and (c) determination of the expression of fatty acid synthesis enzymes and targeted metabolomics using a mouse model and human specimens. The expression of MYC was positively associated with that of key fatty acid synthesis genes including ACLY, ACC1, and FASN in prostate cancer TCGA dataset. Chromatin immunoprecipitation revealed Myc occupancy at the promoters of ACLY, ACC1, and FASN. Prostate-specific overexpression of Myc in Hi-Myc transgenic mice resulted in overexpression of ACLY, ACC1, and FASN proteins in neoplastic lesions and increased circulating levels of total free fatty acids. Targeted metabolomics confirmed increased circulating levels of individual fatty acids in the plasma of Hi-Myc mice and human subjects when compared to corresponding controls. Immunohistochemistry also revealed a positive and statistically significant association in expression of Myc with that of ACC1 in human prostate adenocarcinoma specimens. We propose that Myc-regulated fatty acid synthesis is a valid target for therapy and/or prevention of prostate cancer.

Characterization of CiWRI1 from Carya illinoinensis in Seed Oil Biosynthesis

Pecan (Carya illinoinensis) is a widely consumed edible woody oil species that is rich in unsaturated fatty acids (FAs) that are beneficial to human health. However, the genes and mechanisms regulating seed oil biosynthesis in pecan are not well understood. Here, we analyzed the expression patterns of genes involved in seed oil biosynthesis in two different varieties of pecan with distinct fruit maturation schedules and oil contents. We cloned the C. illinoinensis WRINKLED 1 (CiWRI1) gene, a homolog of ArabidopsisWRINKLED1 (AtWRI1), which plays a key role in FA synthesis. Overexpressing CiWRI1 restored lipid synthesis in the Arabidopsiswri1-1 mutant and rescued other phenotypic defects such as plant height, root length, and germination rate, suggesting that CiWRI1 is an ortholog of the AtWRI1 and is involved in the regulation of FA synthesis. To investigate the mechanism of CiWRI1 regulation, we cloned C. illinoinensis BIOTIN CARBOXYL CARRIER PROTEIN ISOFORM2 (CiBCCP2) and determined that the CiWRI1 protein directly binds to an ASML1/WRI1 (AW)-box motif in the CiBCCP2 gene promoter and thereby activates its transcription. CiBCCP2 overexpression partly rescued the phenotypic defects of the wri1-1 mutant, indicating that it is directly regulated by CiWRI1. Thus, de novo FA biosynthesis in seed is conserved across plant species; moreover, CiWRI1 regulates oil synthesis by directly controlling CiBCCP2 expression. These findings present novel potential targets for molecular-marker-assisted breeding of this commercially important plant.

High‐fat diet‐induced inflammation aggravates hepatic steatosis of blunt snout bream ( Megalobrama amblycephala ) through the transcription regulation of fatty acid synthesis and oxidation

High‐fat diet‐induced inflammation aggravates hepatic steatosis of blunt snout bream ( <i>Megalobrama amblycephala</i> ) through the transcription regulation of fatty acid synthesis and oxidation

Effects of different dietary lipid sources on fatty acid composition and gene expression in common carp

The effects of fatty acid composition in artificial feed on the change in the fatty acid composition of carp muscles and the relationship between Δ6-Fad and Elovl5 genes participating in the regulation of fatty acid synthesis were studied. Juveniles were fed three semi-purified diets (D1–D3) for 6 weeks with different lipid sources: D1, fish oil with high highly unsaturated fatty acids (HUFA); D2, corn oil with high linoleic acid (18:2n-6, LA), D3, linseed oil with high α-linolenic acid (18:3n-3, LNA); then, samples were taken to explore the molecular mechanism and the factors which affect the synthesis of carp HUFA. The content of LA and arachidonic acid (20:4n-6, AA) in common carp fed Diet 2 was higher than in carp receiving D3 (P &amp;lt; 0.05), but the contents of eicosapentaenoic acid (20:5n-3, EPA) and docosahexaenoic acid (22:6n-3, DHA) were lower than in carp fed D1 and D2 (P &amp;lt; 0.05). The liver transcript abundance of Δ6-Fad and Elovl5 in fish fed D2 and D3 at the end of 6 weeks was generally higher than the abundance in the initial stage and in the fish fed D1 (P &amp;lt; 0.05). The results suggest that the common carp can biosynthesise HUFA, and the type and content of fatty acids in feed affected not only the composition and content of fatty acids in common carp muscles, but also the Δ6-Fad and Elovl5 gene expression involved in the biosynthesis of HUFA. Feeding high levels of n-3 HUFA diet can increase the body content of EPA and DHA in common carp. The results of this research may provide a theoretical basis for choosing an appropriate source of lipid for common carp feeds.

Recent development in acetyl-CoA carboxylase inhibitors and their potential as novel drugs.

Acetyl-CoA carboxylase (ACC), a critical enzyme in the regulation of fatty acid synthesis and metabolism, has emerged as an attractive target for a plethora of emerging diseases, such as diabetes mellitus, nonalcoholic fatty liver disease, cancer, bacterial infections and so on. With decades of efforts in medicinal chemistry, significant progress has been made toward the design and discovery of a considerable number of inhibitors of this enzyme. In this review, we not only clarify the role of ACC in emerging diseases, but also summarize recent developments of potent ACC inhibitors and discuss their molecular mechanisms of action and potentials as novel drugs as well as future perspectives toward the design and discovery of novel ACC inhibitors.