Glucagon regulates hepatic lipid metabolism via cAMP and Insig-2 signaling: implication for the pathogenesis of hypertriglyceridemia and hepatic steatosis

Insulin induced gene-2 (Insig-2) is an ER-resident protein that inhibits the activation of sterol regulatory element-binding proteins (SREBPs). However, cellular factors that regulate Insig-2 expression have not yet been identified. Here we reported that cyclic AMP-responsive element-binding protein H (CREBH) positively regulates mRNA and protein expression of a liver specific isoform of Insig-2, Insig-2a, which in turn hinders SREBP-1c activation and inhibits hepatic de novo lipogenesis. CREBH binds to the evolutionally conserved CRE-BP binding elements located in the enhancer region of Insig-2a and upregulates its mRNA and protein expression. Metabolic hormone glucagon and nutritional fasting activated CREBH, which upregulated expression of Insig-2a in hepatocytes and inhibited SREBP-1c activation. In contrast, genetic depletion of CREBH decreased Insig-2a expression, leading to the activation of SREBP-1c and its downstream lipogenic target enzymes. Compromising CREBH-Insig-2 signaling by siRNA interference against Insig-2 also disrupted the inhibitory effect of this signaling pathway on hepatic de novo triglyceride synthesis. These actions resulted in the accumulation of lipid droplets in hepatocytes and systemic hyperlipidemia. Our study identified CREBH as the first cellular protein that regulates Insig-2a expression. Glucagon activated the CREBH-Insig-2a signaling pathway to inhibit hepatic de novo lipogenesis and prevent the onset of hepatic steatosis and hypertriglyceridemia

RNA-Seq Transcriptome Analysis of Rice Primary Roots Reveals the Role of Flavonoids in Regulating the Rice Primary Root Growth

Flavonoids play important roles in root development and in its tropic responses, whereas the flavonoids-mediated changes of the global transcription levels during root growth remain unclear. Here, the global transcription changes in quercetin-treated rice primary roots were analyzed. Quercetin treatment significantly induced the inhibition of root growth and the reduction of H2O2 and O2− levels. In addition, the RNA-seq analysis revealed that there are 1243 differentially expressed genes (DEGs) identified in quercetin-treated roots, including 1032 up-regulated and 211 down-regulated genes. A gene ontology (GO) enrichment analysis showed that the enriched GO terms are mainly associated with the cell wall organization, response to oxidative stress, and response to hormone stimulus. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway analysis showed that the enriched DEGs are involved in phenylpropanoid biosynthesis, glutathione metabolism, and plant hormone signal transduction. Moreover, the quercetin treatment led to an increase of the antioxidant enzyme activities of catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD) in rice roots. Also, the quercetin treatment altered the DR5:GUS expression pattern in the root tips. All of these data indicated that the flavonoids-mediated transcription changes of genes are related to the genes involved in cell wall remodeling, redox homeostasis, and auxin signaling, leading to a reduced cell division in the meristem zone and cell elongation in the elongation zone of roots

Activation of hepatic CREBH and Insig signaling in the anti-hypertriglyceridemic mechanism of R-α-lipoic acid

The activation of sterol regulatory element binding proteins (SREBPs) is regulated by insulin-induced genes-1 and -2 (Insig-1 and Insig-2) and SCAP. We previously reported that feeding R-α-lipoic acid (LA) to Zucker Diabetic Fatty (ZDF) rats improves severe hypertriglyceridemia. In this study, we investigated the role of cAMP-responsive element-binding protein H (CREBH) in the lipid-lowering mechanism of LA and its involvement in the SREBP-1c and Insig pathway. Incubation of McA cells with LA (0.2 mM) or glucose (6 mM) stimulated activation of CREBH. LA treatment further induced mRNA expression of Insig-1 and Insig-2a, but not Insig-2b, in glucose-treated cells. In vivo, feeding LA to obesity-induced hyperlipidemic ZDF rats activated hepatic CREBH and stimulated transcription and translation of Insig-1 and Insig-2a. Activation of CREBH and Insigs induced by LA suppressed processing of SREBP-1c precursor into nuclear SREBP-1c, which subsequently inhibited expression of genes involved in fatty acid synthesis, including FASN, ACC and SCD-1, and reduced triglyceride contents in both glucose-treated cells and ZDF rat livers. Additionally, LA treatment also decreased abundances of very-low-density lipoprotein (VLDL)-associated apolipoproteins, apoB100 and apoE, in glucose-treated cells and livers of ZDF rats, leading to decreased secretion of VLDL and improvement of hypertriglyceridemia. This study unveils a novel molecular mechanism whereby LA lowers triglyceride via activation of hepatic CREBH and increased expression of Insig-1 and Insig-2a to inhibit de novo lipogenesis and VLDL secretion. These findings provide novel insight into the therapeutic potential of LA as an anti–hypertriglyceridemia dietary molecule

Glucagon regulates hepatic lipid metabolism via cAMP and Insig-2 signaling: implication for the pathogenesis of hypertriglyceridemia and hepatic steatosis

Insulin induced gene-2 (Insig-2) is an ER-resident protein that inhibits the activation of sterol regulatory element-binding proteins (SREBPs). However, cellular factors that regulate Insig-2 expression have not yet been identified. Here we reported that cyclic AMP-responsive element-binding protein H (CREBH) positively regulates mRNA and protein expression of a liver specific isoform of Insig-2, Insig-2a, which in turn hinders SREBP-1c activation and inhibits hepatic de novo lipogenesis. CREBH binds to the evolutionally conserved CRE-BP binding elements located in the enhancer region of Insig-2a and upregulates its mRNA and protein expression. Metabolic hormone glucagon and nutritional fasting activated CREBH, which upregulated expression of Insig-2a in hepatocytes and inhibited SREBP-1c activation. In contrast, genetic depletion of CREBH decreased Insig-2a expression, leading to the activation of SREBP-1c and its downstream lipogenic target enzymes. Compromising CREBH-Insig-2 signaling by siRNA interference against Insig-2 also disrupted the inhibitory effect of this signaling pathway on hepatic de novo triglyceride synthesis. These actions resulted in the accumulation of lipid droplets in hepatocytes and systemic hyperlipidemia. Our study identified CREBH as the first cellular protein that regulates Insig-2a expression. Glucagon activated the CREBH-Insig-2a signaling pathway to inhibit hepatic de novo lipogenesis and prevent the onset of hepatic steatosis and hypertriglyceridemia

Research on obstacle avoidance control method of multi-rotor aircraft in coal mine

Multi-rotor aircraft has a good application prospect in coal mine production inspection because of its advantages of simple structure, hovering and multi-directional flight. However, multi-rotor aircraft moves at a high speed, and the aircraft is easily influenced by various external factors during flying. It is difficult to establish a precise mathematical model. The design of a flight control algorithm is complicated. The existing synchronous positioning and map construction method based on laser radar is difficult to meet the real-time requirement of rapid flying of the multi-rotor aircraft. In view of the above problems, an obstacle avoidance control method of multi-rotor aircraft in coal mine by using remote virtual control technology is studied. The virtual remote control system of the multi-rotor aircraft in coal mine underground roadway is constructed. The virtual roadway model and the global navigation map are established in the virtual remote control system according to the initial information of the coal mine roadway. The known static obstacle information in the moving process of the aircraft is obtained, and the known static environment model is established. The task quantity of environment perception modeling in the moving process of the multi-rotor aircraft is reduced, and the operation efficiency of virtual remote control can be improved. In the inspection process, the multi-rotor aircraft detects dynamic obstacle information in the moving direction through sensing equipment carried by the multi-rotor aircraft. The remote control system reconstructs the dynamic obstacle information in an initial virtual roadway model in real-time according to obstacle data. The virtual environment state is updated in real-time to provide a reliable environment basis for local obstacle avoidance control of the aircraft. The remote control system uses the compound virtual force field (CVFF) obstacle avoidance control algorithm to plan the obstacle avoidance path by reading the positioning data and moving speed information of obstacles and aircraft. If the obstacle in front is detected to pose a great threat to the movement of the aircraft, the remote controller can implement remote intervention on the aircraft according to the planned obstacle avoidance path. The system realizes autonomous obstacle avoidance flight and human remote intervention control. In order to improve the perception efficiency and accuracy of aircraft to dynamic obstacles, a CVFF obstacle avoidance control algorithm is studied based on virtual force field (VFF) algorithm by introducing the influence of relative velocity between aircraft and obstacles and target points. The CVFF obstacle avoidance control algorithm is verified by simulation from two aspects of static and dynamic obstacle avoidance paths. The results show that under static conditions, compared with the VFF algorithm, the CVFF algorithm reduces the number of iterations and also shortens the trajectory length of the aircraft. Under dynamic conditions, the aircraft successfully avoids the two dynamic obstacles set in advance and successfully reaches the set target point. The effectiveness of the obstacle avoidance control method of multi-rotor aircraft using the CVFF algorithm is verified

Transcriptomic Analysis of Long Non-Coding RNAs and Coding Genes Uncovers a Complex Regulatory Network That Is Involved in Maize Seed Development

Long non-coding RNAs (lncRNAs) have been reported to be involved in the development of maize plant. However, few focused on seed development of maize. Here, we identified 753 lncRNA candidates in maize genome from six seed samples. Similar to the mRNAs, lncRNAs showed tissue developmental stage specific and differential expression, indicating their putative role in seed development. Increasing evidence shows that crosstalk among RNAs mediated by shared microRNAs (miRNAs) represents a novel layer of gene regulation, which plays important roles in plant development. Functional roles and regulatory mechanisms of lncRNAs as competing endogenous RNAs (ceRNA) in plants, particularly in maize seed development, are unclear. We combined analyses of consistently altered 17 lncRNAs, 840 mRNAs and known miRNA to genome-wide investigate potential lncRNA-mediated ceRNA based on “ceRNA hypothesis”. The results uncovered seven novel lncRNAs as potential functional ceRNAs. Functional analyses based on their competitive coding-gene partners by Gene Ontology (GO) and KEGG biological pathway demonstrated that combined effects of multiple ceRNAs can have major impacts on general developmental and metabolic processes in maize seed. These findings provided a useful platform for uncovering novel mechanisms of maize seed development and may provide opportunities for the functional characterization of individual lncRNA in future studies

ZmSOC1, a MADS-Box Transcription Factor from Zea mays, Promotes Flowering in Arabidopsis

Zea mays is an economically important crop, but its molecular mechanism of flowering remains largely uncharacterized. The gene, SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1), integrates multiple flowering signals to regulate floral transition in Arabidopsis. In this study, ZmSOC1 was isolated from Zea mays. Sequence alignment and phylogenetic analysis demonstrated that the ZmSOC1 protein contained a highly conserved MADS domain and a typical SOC1 motif. ZmSOC1 protein was localized in the nucleus in protoplasts and showed no transcriptional activation activity in yeast cells. ZmSOC1 was highly expressed in maize reproductive organs, including filaments, ear and endosperm, but expression was very low in embryos; on the other hand, the abiotic stresses could repress ZmSOC1 expression. Overexpression of ZmSOC1 resulted in early flowering in Arabidopsis through increasing the expression of AtLFY and AtAP1. Overall, these results suggest that ZmSOC1 is a flowering promoter in Arabidopsis