Project description:Cysteine dioxygenase type 1 (Cdo1) is a key enzyme for cysteine catabolism that is enriched in liver, whose role in NAFLD remains poorly understood. Here, we show that exercise induces the expression of hepatic Cdo1 via the cAMP/PKA/CREB signaling pathway. Hepatocyte-specific knockout of Cdo1 (Cdo1LKO) impairs the effect of exercise against NAFLD, whereas hepatocyte-specific overexpression of Cdo1 (Cdo1LTG) and exercise synergistically ameliorates NAFLD in male mice. Mechanistically, Cdo1 facilitates the binding between AMPK and kinase active Camkk2, which activates AMPK signaling. This promotes fatty acid oxidation and mitochondrial biogenesis in hepatocytes to attenuate hepatosteatosis. Therefore, by promoting hepatic Camkk2-AMPK signaling pathway, Cdo1 acts as an important downstream effector of exercise to combat against NAFLD
Project description:Citrus greening or huanglongbing (HLB) disease is caused by Candidatus liberibacter asiaticus (CLas) and associated with an increase in pre-harvest fruit drop, for which the molecular mechanisms remain unknown. In order to understand the molecular basis of the HLB-associated fruit abscission, by means of RNA-Sequencing analysis (RNA-Seq), transcriptomes in citrus calyx abscission zones were analyzed and compared among fruit dropped (D) or retained (R) from healthy (h) or HLB-diseased (d) trees upon shaking the trees. Cluster analysis based on the transcript reads indicates that dropped fruit from HLB-diseased trees (Dd) have largest distances from all other groups. Differentially expressed genes (DEGs) were identified between Dd and Rd, Dh and Rh, Rd and Rh, Dd and Dh. Wilcoxon test of the whole dataset of DEGs revealed that consistently up-regulated genes in Dd versus Rd and Dd versus Dh are in the functional categories of “secondary metabolism, lipid metabolism and hormone-ethylene and –jasmonate”; while those down-regulated genes didn’t show clear pattern of regulation. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses indicated that the significant biological processes or pathways involved in HLB-related fruit abscission were those related to defense response, secondary metabolism and hormone signaling. Among them, “response to chitin” was the most significant (p= 9.95E-13) biological process, and “jasmonic acid biosynthesis” was the most significant (p= 4.6E-5) pathway. Genes related to synthesis and signaling of ethylene (ET) and jasmonate (JA) were consistently up-regulated, while abscisic acid, auxin, brassinosteroid, cytokinin, and gibberellin were generally down-regulated in Dd; but not in Dh. Consistent with the transcriptomic data, fruit ethylene production was detected in two third of the Dd fruit, but none of Rd, Dh or Rh fruit. And, in agreement with the hormone expression profiles, substantial numbers of downstream JA/ET-responsive defense related genes were up-regulated in Dd, but not in Dh. Thirty representative DEGs covering categories of hormone, secondary metabolism, and JA/ET responsive defense responses were verified by qRT-PCR. The results indicate that HLB-associated pre-harvest fruit abscission is mediated by JA/ET signaling, which has been known to be triggered by infection of necrotrophic pathogens.
Project description:Non-alcoholic fatty liver disease (NAFLD) is a chronic disease caused by hepatic steatosis. Adenosine deaminases acting on RNA (ADARs) catalyze adenosine to inosine RNA editing. However, the functional role of ADAR2 in NAFLD is unclear. ADAR2+/+/GluR-BR/R mice (wild type, WT) and ADAR2−/−/GluR-BR/R mice (ADAR2 KO) mice were fed with standard chow or high-fat diet (HFD) for 12 weeks. ADAR2 KO mice exhibited protection against HFD–induced glucose intolerance, insulin resistance, and dyslipidemia. Moreover, ADAR2 KO mice displayed reduced liver lipid droplets in concert with decreased hepatic TG content, improved hepatic insulin signaling, better pyruvate tolerance, and increased glycogen synthesis. Mechanistically, ADAR2 KO effectively mitigated excessive lipid production via AMPK/Sirt1 pathway. ADAR2 KO inhibited hepatic gluconeogenesis via the AMPK/CREB pathway and promoted glycogen synthesis by activating the AMPK/GSK3β pathway. These results provided novel evidence that ADAR2 KO protected against NAFLD progression through activation of AMPK signaling pathways.
Project description:To excavate the underlying molecular regulation network that during citrus fruit development and ripening, we used RNA-seq to generate high-resolution profiles of global gene expression in four different fruit tissues at six development stages. Using weighted gene coexpression network analysis, we identified modules of coexpressed genes and hub genes of tissue-specific networks. In general, this study was aimed to uncover the new molecular insights into citrus fruit development and ripening, and to reveal the specific nonclimacteric characteristics of citrus fruit.
Project description:Background: Magnesium (Mg)-deficiency occurs most frequently in strongly acidic, sandy soils. Citrus are grown mainly on acidic and strong acidic soils. Mg-deficiency causes poor fruit quality and low fruit yield in some Citrus orchards. For the first time, we investigated Mg-deficiency-responsive miRNAs in ‘Xuegan’ (Citrus sinensis) roots using Illumina sequencing in order to obtain some miRNAs presumably responsible for Citrus Mg-deficiency tolerance. Results: We obtained 101 (69) miRNAs with increased (decreased) expression from Mg-starved roots. Our results suggested that the adaptation of Citrus roots to Mg-deficiency was related to the several aspects: (a) inhibiting root respiration and related gene expression via inducing miR158 and miR2919; (b) enhancing antioxidant system by down-regulating related miRNAs (miR780, miR6190, miR1044, miR5261 and miR1151) and the adaptation to low-phosphorus (miR6190); (c) activating transport-related genes by altering the expression of miR6190, miR6485, miR1044, miR5029 and miR3437; (d) elevating protein ubiquitination due to decreased expression levels of miR1044, miR5261, miR1151 and miR5029; (e) maintaining root growth by regulating miR5261, miR6485 and miR158 expression; and (f) triggering DNA repair (transcription regulation) by regulating miR5176 and miR6485 (miR6028, miR6190, miR6485, miR5621, miR160 and miR7708) expression. Mg-deficiency-responsive miRNAs involved in root signal transduction also had functions in Citrus Mg-deficiency tolerance. Conclusions: We obtained several novel Mg-deficiency-responsive miRNAs (i.e., miR5261, miR158, miR6190, miR6485, miR1151 and miR1044) possibly contributing to Mg-deficiency tolerance. These results revealed some novel clues on the miRNA-mediated adaptation to nutrient deficiencies in higher plants.
Project description:Fruit ripening in Citrus is not well understood at the molecular level. Knowledge of the regulatory mechanism of citrus fruit ripening at the post-transcriptional level in particular is lacking. Here, we comparatively analyzed the miRNAs and their targeted genes in a spontaneous late-ripening mutant, ?Fengwan? sweet orange (MT) (Citrus sinensis L. Osbeck), and its wild-type counterpart ('Fengjie 72-1', WT). Using high-throughput sequencing of small RNAs and RNA degradome tags, we identified 107 known and 21 novel miRNAs, as well as 225 target genes. A total of 24 miRNAs (16 known miRNAs and 8 novel miRNAs) were shown to be differentially expressed between MT and WT. The expression pattern of several key miRNAs and their target genes during citrus fruit development and ripening stages was examined. Csi-miR156k, csi-miR159 and csi-miR166d suppressed specific transcription factors (GAMYBs, SPLs and ATHBs) that are supposed to be important regulators involved in citrus fruit development and ripening. In the present study, miRNA-mediated silencing of target genes was found under complicated and sensitive regulation in citrus fruit. The identification of miRNAs and their target genes provide new clues for future investigation of mechanisms that regulate citrus fruit ripening.
Project description:Citrate is demonstrated to be an indispensable secondary metabolite in citrus fruit. Citrus citrate content is affected by accumulation, degradation, usage, transport and storage. The detail mechanisms of citrate accumulation are complicated in citrus fruit and there are other regulating pathways that have yet to be discovered. In this study, we utilized genomic expression investigation to gain a deep insight into the citrate-accumulation-related biological processes in sweet orange.
Project description:To identify genes associated with citrus peel development and manifestation of peel disorders, we analyzed flavedo, albedo and juice sac tissues from five types of citrus fruit including, mandarin orange, navel orange, valencia orange, grapefruit and lemon. Fruits of five different citrus cultivars. Mature, healthy fruits of five different citrus cultivars (M-bM-^@M-^\ValenciaM-bM-^@M-^] and M-bM-^@M-^\NavelM-bM-^@M-^] orange [Citrus sinensis], mandarin [Citrus reticulata], lemon [Citrus M-CM-^W limon], grapefruit [Citrus M-CM-^W paradisi]) were purchased from a food market located in Davis, CA, USA. For all five types of fruit, three tissues (flavedo, albedo, and juice sacs) were compared separately. Each of the three tissues from each of the five types of fruit were sampled in three biological replicates, for a total of 45 samples. Samples were prepared from a 1 cm-thick equatorial disc and four sections (N, S, E, and W) were cut. Each section of flavedo, albedo, and juice sac tissue was dissected. gene expression variation underlying quality trait, different genotypes