ZmBELL10 interacts with other ZmBELLs and recognizes specific motifs for transcriptional activation to modulate internode patterning in maize.

Plant height is an important agronomic trait that affects crop yield. Elucidating the molecular mechanism underlying plant height regulation is also an important question in developmental biology. Here, we report that a BELL transcription factor, ZmBELL10, positively regulates plant height in maize (Zea mays). Loss of ZmBELL10 function resulted in shorter internodes, fewer nodes, and smaller kernels, while ZmBELL10 overexpression increased plant height and hundred-kernel weight. Transcriptome analysis and chromatin immunoprecipitation followed by sequencing showed that ZmBELL10 recognizes specific sequences in the promoter of its target genes and activates cell division- and cell elongation-related gene expression, thereby influencing node number and internode length in maize. ZmBELL10 interacted with several other ZmBELL proteins via a spatial structure in its POX domain to form protein complexes involving ZmBELL10. All interacting proteins recognized the same DNA sequences, and their interaction with ZmBELL10 increased target gene expression. We identified the key residues in the POX domain of ZmBELL10 responsible for its protein-protein interactions, but these residues did not affect its transactivation activity. Collectively, our findings shed light on the functions of ZmBELL10 protein complexes and provide potential targets for improving plant architecture and yield in maize.

A spatiotemporal transcriptomic network dynamically modulates stalk development in maize.

Maize (Zea mays) is an important cereal crop with suitable stalk formation which is beneficial for acquiring an ideal agronomic trait to resist lodging and higher planting density. The elongation pattern of stalks arises from the variable growth of individual internodes driven by cell division and cell expansion comprising the maize stalk. However, the spatiotemporal dynamics and regulatory network of the maize stalk development and differentiation process remain unclear. Here, we report spatiotemporally resolved transcriptomes using all internodes of the whole stalks from developing maize at the elongation and maturation stages. We identified four distinct groups corresponding to four developmental zones and nine specific clusters with diverse spatiotemporal expression patterns among individual internodes of the stalk. Through weighted gene coexpression network analysis, we constructed transcriptional regulatory networks at a fine spatiotemporal resolution and uncovered key modules and candidate genes involved in internode maintenance, elongation, and division that determine stalk length and thickness in maize. Further CRISPR/Cas9-mediated knockout validated the function of a cytochrome P450 gene, ZmD1, in the regulation of stalk length and thickness as predicted by the WGCN. Collectively, these results provide insights into the high genetic complexity of stalk development and the potentially valuable resources with ideal stalk lengths and widths for genetic improvements in maize.

Dietary Supplementation of Vine Tea Ameliorates Glucose and Lipid Metabolic Disorder via Akt Signaling Pathway in Diabetic Rats.

A traditional Chinese tea with many pharmacological effects, vine tea (VT) is considered a potential dietary supplement to improve type 2 diabetes (T2D). To investigate the effect and mechanism of VT on glucose and lipid metabolic disorders in T2D rats, Wistar rats fed a normal diet served as the normal control, while rats fed a high-fat diet combined with low-dose streptozotocin (STZ)-induced T2D were divided into three groups: The model group (MOD); the positive control group (MET, metformin at 200 mg/kg/d); and the VT-treated group (VT500, allowed to freely drink 500 mg/L VT). After four weeks of intervention, biochemical metrics indicated that VT significantly ameliorated hyperglycemia, hyperlipidemia and hyperinsulinemia in T2D rats. Metabolomics research indicated that VT regulated the levels of metabolites closely related to glucose and lipid metabolism and promoted glycogen synthesis. Furthermore, VT had a significant influence on the expression of key genes involved in the Akt signaling pathway, inhibited gluconeogenesis through the Akt/Foxo1/Pck2 signaling pathway, and reduced fatty acid synthesis via the SREBP1c/Fasn signaling pathways. In conclusion, VT has great potential as a dietary supplement to ameliorate glucose and lipid metabolic disorders via the Akt signaling pathway in T2D rats.

Generation and analysis of the Rett syndrome-associated MeCP2- null rat model.

MeCP2 mutations are associated with the Rett syndrome (RTT). Currently, there is an urgent need for new animal models for RTT as the existing MeCP2 knockout mouse models fail to fully mimic the pathogenesis and symptoms of RTT patients. In order to investigate the role of MeCP2 in brain development and RTT pathogenesis, we aimed to set up the MeCP2-null rat model using the CRISPR/Cas9 technology. Firstly we constructed the MeCP2 targeting vector and then microinjected Cas9 mRNA and sgRNA mixtures into fertilized ova of SD rats. The sgRNA was designed to target the exon 2 of MeCP2. Next, knockout rats were confirmed using DNA sequencing and Western blotting. Lastly, phenotypes including growth and behaviors of MeCP2 knockout rats were analyzed. The results indicated that the MeCP2 knockout rats showed body weight loss, anxiety tendency and cognitive deficits. The MeCP2-null rat model established in this study recapitulates the major symptoms of RTT patients and provides an alternative tool for future studies of MeCP2 functions.

[Research strategy of traditional Chinese medicine proteomics].

The application of proteomics in the research of traditional Chinese medicine (TCM) is very extensive, and there have been many successful cases. In this paper, the previous studies on the complex system of TCM by using proteomics technology were reviewed, and the authors proposed to set up a special subject on proteomics in TCM, which is called TCM proteomics. In this paper, the research strategies and the future research directions of TCM proteomics were reviewed and discussed, which may provide some ideas for the researchers of TCM proteomics.

Cajaninstilbene acid prevents corticosterone-induced apoptosis in PC12 cells by inhibiting the mitochondrial apoptotic pathway.

BACKGROUND/AIMS: Cajaninstilbene acid (3-hydroxy-4-prenyl-5-methoxystilben-2 -carboxylic acid, CSA), a natural stilbene isolated from the leaves of Cajanus cajan, has attracted considerable attention for its wide range of pharmacological activities. This study investigated whether CSA protects against corticosterone (CORT)-induced injury in PC12 cells and examined the potential mechanisms underlying this protective effect. METHODS: Cell viability and cytotoxicity were detected using a 3-(4,5-desethyithiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and a lactate dehydrogenase (LDH) assay kit, respectively. PC12 cell apoptosis was measured using Hoechst 33342 staining and a DNA fragmentation assay kit, and intracellular Ca(2+) concentrations were assessed by fluorescent labelling. Next, the mitochondrial permeability transition pores (mPTPs) and mitochondrial membrane potentials (∆Ψm) were detected using a colorimetric mPTP detection kit and a 5,5',6,6'-tetrachloro-1,1',3,3'- tetraethylbenzimidazolyl-carbocyanine iodide (JC-1) kit, respectively. Finally, cytochrome c, caspase-3 and inhibitor of caspase-activated deoxyribonuclease (ICAD) expression levels were monitored by western blot analysis. RESULTS: Treatment with 100 µmol/l CORT induced cytotoxicity in PC12 cells. However, CSA dose-dependently increased cell viability and decreased LDH release as well as CORT-induced apoptosis. Mechanistically, compared with the CORT-treated group, CSA strongly attenuated intracellular Ca(2+) overload and restored mitochondrial functions, including mPTPs and ∆Ψm. Furthermore, the down-regulation of cytochrome c and ICAD protein expression and the blockage of caspase-3 activity were observed upon CSA treatment. CONCLUSIONS: In summary, our data are the first to show that the in vitro antidepressant-like effect of CSA may be attributed to the cytoprotection of neurons and that such neuroprotective mechanisms are correlated with intracellular Ca(2+) homeostasis and mitochondrial apoptotic pathways.

Epigenetic variation in maize agronomical traits for breeding and trait improvement.

Epigenetics-mediated breeding (Epibreeding) involves engineering crop traits and stress responses through the targeted manipulation of key epigenetic features to enhance agricultural productivity. While conventional breeding methods raise concerns about reduced genetic diversity, epibreeding propels crop improvement through epigenetic variations that regulate gene expression, ultimately impacting crop yield. Epigenetic regulation in crops encompasses various modes, including histone modification, DNA modification, RNA modification, non-coding RNA, and chromatin remodeling. This review summarizes the epigenetic mechanisms underlying major agronomic traits in maize and identifies candidate epigenetic landmarks in the maize breeding process. We propose a valuable strategy for improving maize yield through epibreeding, combining CRISPR/Cas-based epigenome editing technology and Synthetic Epigenetics (SynEpi). Finally, we discuss the challenges and opportunities associated with maize trait improvement through epibreeding.

The trxG protein ULT1 regulates Arabidopsis organ size by interacting with TCP14/15 to antagonize the LIM peptidase DA1 for H3K4me3 on target genes.

Plant organ size is an important agronomic trait that makes a significant contribution to plant yield. Despite its central importance, the genetic and molecular mechanisms underlying organ size control remain to be fully clarified. Here, we report that the trithorax group protein ULTRAPETALA1 (ULT1) interacts with the TEOSINTE BRANCHED1/CYCLOIDEA/PCF14/15 (TCP14/15) transcription factors by antagonizing the LIN-11, ISL-1, and MEC-3 (LIM) peptidase DA1, thereby regulating organ size in Arabidopsis. Loss of ULT1 function significantly increases rosette leaf, petal, silique, and seed size, whereas overexpression of ULT1 results in reduced organ size. ULT1 associates with TCP14 and TCP15 to co-regulate cell size by affecting cellular endoreduplication. Transcriptome analysis revealed that ULT1 and TCP14/15 regulate common target genes involved in endoreduplication and leaf development. ULT1 can be recruited by TCP14/15 to promote lysine 4 of histone H3 trimethylation at target genes, activating their expression to determine final cell size. Furthermore, we found that ULT1 influences the interaction of DA1 and TCP14/15 and antagonizes the effect of DA1 on TCP14/15 degradation. Collectively, our findings reveal a novel epigenetic mechanism underlying the regulation of organ size in Arabidopsis.

Integration of high-throughput phenotyping, GWAS, and predictive models reveals the genetic architecture of plant height in maize.

Plant height (PH) is an essential trait in maize (Zea mays) that is tightly associated with planting density, biomass, lodging resistance, and grain yield in the field. Dissecting the dynamics of maize plant architecture will be beneficial for ideotype-based maize breeding and prediction, as the genetic basis controlling PH in maize remains largely unknown. In this study, we developed an automated high-throughput phenotyping platform (HTP) to systematically and noninvasively quantify 77 image-based traits (i-traits) and 20 field traits (f-traits) for 228 maize inbred lines across all developmental stages. Time-resolved i-traits with novel digital phenotypes and complex correlations with agronomic traits were characterized to reveal the dynamics of maize growth. An i-trait-based genome-wide association study identified 4945 trait-associated SNPs, 2603 genetic loci, and 1974 corresponding candidate genes. We found that rapid growth of maize plants occurs mainly at two developmental stages, stage 2 (S2) to S3 and S5 to S6, accounting for the final PH indicators. By integrating the PH-association network with the transcriptome profiles of specific internodes, we revealed 13 hub genes that may play vital roles during rapid growth. The candidate genes and novel i-traits identified at multiple growth stages may be used as potential indicators for final PH in maize. One candidate gene, ZmVATE, was functionally validated and shown to regulate PH-related traits in maize using genetic mutation. Furthermore, machine learning was used to build predictive models for final PH based on i-traits, and their performance was assessed across developmental stages. Moderate, strong, and very strong correlations between predictions and experimental datasets were achieved from the early S4 (tenth-leaf) stage. Colletively, our study provides a valuable tool for dissecting the spatiotemporal formation of specific internodes and the genetic architecture of PH, as well as resources and predictive models that are useful for molecular design breeding and predicting maize varieties with ideal plant architectures.

Genomic, transcriptomic, and epigenomic analysis of a medicinal snake, Bungarus multicinctus, to provides insights into the origin of Elapidae neurotoxins.

The many-banded krait, Bungarus multicinctus, has been recorded as the animal resource of JinQianBaiHuaShe in the Chinese Pharmacopoeia. Characterization of its venoms classified chief phyla of modern animal neurotoxins. However, the evolutionary origin and diversification of its neurotoxins as well as biosynthesis of its active compounds remain largely unknown due to the lack of its high-quality genome. Here, we present the 1.58 Gbp genome of B. multicinctus assembled into 18 chromosomes with contig/scaffold N50 of 7.53 Mbp/149.8 Mbp. Major bungarotoxin-coding genes were clustered within genome by family and found to be associated with ancient local duplications. The truncation of glycosylphosphatidylinositol anchor in the 3'-terminal of a LY6E paralog released modern three-finger toxins (3FTxs) from membrane tethering before the Colubroidea divergence. Subsequent expansion and mutations diversified and recruited these 3FTxs. After the cobra/krait divergence, the modern unit-B of ß-bungarotoxin emerged with an extra cysteine residue. A subsequent point substitution in unit-A enabled the ß-bungarotoxin covalent linkage. The B. multicinctus gene expression, chromatin topological organization, and histone modification characteristics were featured by transcriptome, proteome, chromatin conformation capture sequencing, and ChIP-seq. The results highlighted that venom production was under a sophisticated regulation. Our findings provide new insights into snake neurotoxin research, meanwhile will facilitate antivenom development, toxin-driven drug discovery and the quality control of JinQianBaiHuaShe.

Sanwei sandalwood decoction ameliorates acute ischemiareperfusion injury in rats by modulating myocyte electrophysiological characteristics.

Sanwei sandalwood decoction (SWTX) is a classical Chinese medicine formula and clinically effective treatment for coronary heart disease, including myocardial ischemia/reperfusion (I/R) injury. Because the treatment mechanism of SWTX in I/R injury remains obscure, we intended to analyze the potential cardioprotective effects of SWTX in rats with myocardial I/R injury. Our research revealed that SWTX prolonged ventricular conduction time in a dose-dependent manner. While SWTX significantly delayed left ventricular signal conduction velocity, it had no effect on left atrial conduction velocity. Under sinus conditions, low SWTX concentrations reduced left ventricular conduction dispersion, while high concentrations increased conduction dispersion. SWTX also prolonged the QRS interval, APD30/50/90, and ERP. In whole-cell patch clamp experiments on myocytes, Ito and Ikr were inhibited by SWTX. While SWTX had no effect on INa, the activation curve for Nav1.5 was left-shifted. Finally, SWTX reduced the probability of ventricular fibrillation and suppressed early and late depolarization in an acute I/R injury rat model. These findings shed light on the mechanism by which SWTX alleviates myocardial I/R injury.

RNA 5-Methylcytosine Modification Regulates Vegetative Development Associated with H3K27 Trimethylation in Arabidopsis.

Methylating RNA post-transcriptionally is emerging as a significant mechanism of gene regulation in eukaryotes. The crosstalk between RNA methylation and histone modification is critical for chromatin state and gene expression in mammals. However, it is not well understood mechanistically in plants. Here, the authors report a genome-wide correlation between RNA 5-cytosine methylation (m5 C) and histone 3 lysine27 trimethylation (H3K27me3) in Arabidopsis. The plant-specific Polycomb group (PcG) protein EMBRYONIC FLOWER1 (EMF1) plays dual roles as activators or repressors. Transcriptome-wide RNA m5 C profiling revealed that m5 C peaks are mostly enriched in chromatin regions that lacked H3K27me3 in both wild type and emf1 mutants. EMF1 repressed the expression of m5 C methyltransferase tRNA specific methyltransferase 4B (TRM4B) through H3K4me3, independent of PcG-mediated H3K27me3 mechanism. The 5-Cytosine methylation on targets is increased in emf1 mutants, thereby decreased the mRNA transcripts of photosynthesis and chloroplast genes. In addition, impairing EMF1 activity reduced H3K27me3 levels of PcG targets, such as starch genes, which are de-repressed in emf1 mutants. Both EMF1-mediated promotion and repression of gene activities via m5 C and H3K27me3 are required for normal vegetative growth. Collectively, t study reveals a previously undescribed epigenetic mechanism of RNA m5 C modifications and histone modifications to regulate gene expression in eukaryotes.

NOTCH Signaling Controls Ciliary Body Morphogenesis and Secretion by Directly Regulating Nectin Protein Expression.

Anterior segment dysgenesis is often associated with cornea diseases, cataracts, and glaucoma. In the anterior segment, the ciliary body (CB) containing inner and outer ciliary epithelia (ICE and OCE) secretes aqueous humor that maintains intraocular pressure (IOP). However, CB development and function remain poorly understood. Here, this study shows that NOTCH signaling in the CB maintains the vitreous, IOP, and eye structures by regulating CB morphogenesis, aqueous humor secretion, and vitreous protein expression. Notch2 and Notch3 function via RBPJ in the CB to control ICE-OCE adhesion, CB morphogenesis, aqueous humor secretion, and protein expression, thus maintaining IOP and eye structures. Mechanistically, NOTCH signaling transcriptionally controls Nectin1 expression in the OCE to promote cell adhesion for driving CB morphogenesis and to directly stabilize Cx43 for controlling aqueous humor secretion. Finally, NOTCH signaling directly controls vitreous protein secretion in the ICE. Therefore, this study provides important insight into CB functions and involvement in eye diseases.

Liver Transcriptomic Reveals Novel Pathways of Empagliflozin Associated With Type 2 Diabetic Rats.

The hypoglycaemic target of empagliflozin (EMP), as a novel inhibitor of sodium-glucose cotransporter (SGLT2), is clear. However, recent studies have shown that EMP also has an important role in lipid metabolism and cardiovascular diseases. The liver plays an important role in the development of type 2 diabetes (T2D), although whether EMP affects liver glucose metabolism is currently not reported. This study was designed to evaluate the effect of EMP on hepatic glucose metabolism in T2D and the underlying mechanism. A model of T2D was established by a high-fat and glucose diet (HFD) combined with streptozotocin (30 mg/kg) in male Wistar rats. Serum samples were collected to measure biochemical indicators, and liver samples were extracted for RNA-seq assay. Quantitative real-time PCR (qPCR) was used to further verify the gene expression levels detected by the RNA-seq assay. The EMP group showed significantly decreased blood glucose, triglyceride, cholesterol, non-esterified fatty acid and low-density lipoprotein cholesterol levels, and increased high-density lipoprotein cholesterol levels in serum compared with the type 2 diabetes model (MOD) group. Furthermore, EMP decreased the levels of inflammatory factors IL-1ß, IL-6, and IL-8 in the serum compared to the MOD. Liver transcriptome analysis showed EMP affects a large number of upregulated and downregulated genes. Some of these genes are novel and involve in the metal ion binding pathway and the negative regulation of transcription from the RNA polymerase II promoter pathway, which are also closely related to glucolipid metabolism and insulin signaling. Our study provides new knowledge about the mechanism through which SGLT inhibitor can offer beneficial effects in T2D and especially in the hepatic metabolism. These genes found in this study also laid a solid foundation for further research on the new roles and mechanisms of EMP.

Acteoside From Ligustrum robustum (Roxb.) Blume Ameliorates Lipid Metabolism and Synthesis in a HepG2 Cell Model of Lipid Accumulation.

We aimed to ascertain the mechanism underlying the effects of acteoside (ACT) from Ligustrum robustum (Roxb.) Blume (Oleaceae) on lipid metabolism and synthesis. ACT, a water-soluble phenylpropanoid glycoside, is the most abundant and major active component of L. robustum; the leaves of L. robustum, known as kudingcha (bitter tea), have long been used in China as an herbal tea for weight loss. Recently, based on previous studies, our team reached a preliminary conclusion that phenylpropanoid glycosides from L. robustum most likely contribute substantially to reducing lipid levels, but the mechanism remains unclear. Here, we conducted an in silico screen of currently known phenylethanoid glycosides from L. robustum and attempted to explore the hypolipidemic mechanism of ACT, the representative component of phenylethanoid glycosides in L. robustum, using RNA-seq technology, quantitative real-time PCR (qPCR) and Western blotting. First, the screening results for six compounds were docked with 15 human protein targets, and 3 of 15 protein targets were related to cardiovascular diseases. Based on previous experimental data and docking results, we selected ACT, which exerted positive effects, for further study. We generated a lipid accumulation model using HepG2 cells treated with a high concentration of oleic acid and then extracted RNA from cells treated for 24 h with 50 µmol/L ACT. Subsequently, we performed a transcriptomic analysis of the RNA-seq results, which revealed a large number of differentially expressed genes. Finally, we randomly selected some genes and proteins for further validation using qPCR and Western blotting; the results agreed with the RNA-seq data and confirmed their reliability. In conclusion, our experiments proved that ACT from L. robustum alters lipid metabolism and synthesis by regulating the expression of multiple genes, including Scarb1, Scarb2, Srebf1, Dhcr7, Acat2, Hmgcr, Fdft1, and Lss, which are involved several pathways, such as the glycolytic, AMPK, and fatty acid degradation pathways.

The protective effects of the native flavanone flavanomarein on neuronal cells damaged by 6-OHDA.

BACKGROUND: Flavanomarein is the main component of Coreopsis tinctoria Nutt. (C. tinctoria), which is a globally well-known flower tea that has a distinct flavor and many beneficial health effects, such as antioxidant activities. We aimed to explore the effect of flavanomarein on a 6-hydroxydopamine (6-OHDA)-lesioned cell model of oxidative stress. METHODS: In this study, we used 6-OHDA-lesioned PC12 cells and primary cortical neurons to investigate the protective effects of flavanomarein and its potential mechanism. RESULTS: The results indicated that pretreatment with flavanomarein (25, 50, or 100 µM for 24 h) significantly increased the cell viability, reduced the lactate dehydrogenase (LDH) release and improved the mitochondrial membrane potential (∆Ψm) and mitochondrial impairment. Additionally, flavanomarein markedly reduced the gene expression of tumor necrosis factor (TNF)-α and protein kinase C ζ (PKC-ζ), the nuclear translocation of p65, and the levels of p-AMPK-α and acetyl-p53. Flavanomarein also elevated the gene expression of P85α, PKC-ß1, and Bcl-2, the protein expression of Sirt1 and ICAD, and the phosphorylation level of AKT. CONCLUSIONS: Together, these results suggest that flavanomarein protects PC12 cells and primary cortical neurons from 6-OHDA-induced neurotoxicity by upregulating the PI3K/AKT signaling pathway and attenuating the nuclear factor kappa B (NF-κB) signaling pathway. Therefore, our study provides evidence that may aid in the development of a potential compound against 6-OHDA toxicity.

Eucommia ulmoides Oliv. Leaf Extract Improves Erectile Dysfunction in Streptozotocin-Induced Diabetic Rats by Protecting Endothelial Function and Ameliorating Hypothalamic-Pituitary-Gonadal Axis Function.

Erectile dysfunction (ED) is a major complication of diabetes mellitus. Eucommia ulmoides Oliv. is used as a traditional medicine for male impotence, but no systematic study has examined its effect on diabetes-associated ED. In this study, we investigated the effects of Eucommia ulmoides Oliv. leaf extract (EULE) on restoring erectile function in streptozotocin (STZ)-induced diabetic rats model. After 16 weeks of treatment, EULE administration had significantly increased intracavernosal pressure, nitric oxide (NO) levels, and cyclic guanosine monophosphate (cGMP) concentrations. Serum superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels were markedly higher and serum malondialdehyde (MDA) levels were lower in the EULE-treated groups than in the diabetic model group. EULE restored NO biosynthesis by significantly increasing protein kinase B (Akt) and endothelial NO synthase (eNOS) activation. Furthermore, EULE is likely to benefit the hypothalamic-pituitary-gonadal (HPG) axis, as it increased gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T) concentrations as well as hormone receptors Gnrhr, Fshr, and Lhr expression levels. Hence, EULE attenuates oxidative stress, increases NO production, and activates the Akt-eNOS pathway to restore endothelial function; moreover, EULE enhances the HPG axis to improve erectile function. These results suggest that EULE may represent a new therapeutic avenue for diabetes-associated ED.

Transcriptome analysis reveals the mechanism of the effect of flower tea Coreopsis tinctoria on hepatic insulin resistance.

Non-Camellia tea and herbal medicine help prevent the development of diabetes and other metabolic diseases. Previous studies revealed that Coreopsis tinctoria (CT) flower tea increases insulin sensitivity and, in some high-fat diet (HFD)-fed rats, even prevents hepatic metabolic disorders. However, the molecular mechanisms by which CT improves insulin resistance are not known. In this study, six-week-old rats were fed a normal diet (ND), an HFD or an HFD supplemented with CT for 8 weeks. Serum samples were collected, and the livers were extracted for RNA-seq gene expression analysis. Real-time PCR and western blotting further verified the RNA-seq results. In our results, dietary CT ameliorated HFD-induced hepatosteatosis, glucose intolerance, and insulin resistance. In the HFD group, 1667 differentially expressed genes (DEGs) were identified compared with the ND group. In the CT group, 327 DEGs were identified compared with the HFD group. Some of these DEGs were related to insulin signalling, hepatic lipogenesis and glucose homeostasis. This study suggested that insulin resistance with hyperinsulinaemia, and not insulin insufficiency, is an early problem in HFD-fed rats, and CT downregulates insulin secretion genes (e.g., Rasd1, Stxbp1 and Sfxn1). Hepatic gene and protein expression analyses indicated that the regulatory effects of CT on glucose and lipid homeostasis are likely mediated via the Akt/FoxO1 signalling pathway and are regulated by the transcription factors hairy and enhancer of split 1 (HES1) and small heterodimer partner (SHP). Our study provides transcriptomic evidence of the complex pathogenic mechanism involved in hepatic insulin resistance and proves that supplementation with CT improves insulin resistance at a global scale.

Aerobic exercise improves endothelial function and serum adropin levels in obese adolescents independent of body weight loss.

Adropin is a secreted protein that regulates endothelial function. However, adropin levels in obese adolescent patients are currently uncertain. Therefore, we evaluated the association between plasma adropin levels and vascular endothelial function and investigated the effect of aerobic exercise in obese adolescents. A total of 45 obese adolescents and 20 controls (age 16-19 years) were included in our study. The obese adolescents received 12 weeks of aerobic exercise training. Serum adropin was detected using enzyme-linked immunosorbent assay. Vascular reactive hyperemia indexes (RHIs) were obtained using Endo-PAT2000. Adropin levels and RHI were significantly lower in obese adolescents than in normal-weight adolescents. Adropin levels and RHI increased significantly independently of changes in body weight after an exercise intervention (P < 0.01). Pearson correlation analysis revealed that adropin levels positively correlated with HDL-C levels (r = 0.389, P < 0.01) and RHI (r = 0.32, P < 0.01). Multiple linear stepwise regression analysis showed that the insulin resistance index (t = -3.301, P < 0.01) and HDL-C level (t = 2.620, P = 0.011) were independent risk factors of adropin levels. In addition, Δadropin (t = 3.261, P < 0.01) was an independent influencing factor of ΔRHI. Our findings suggest that adropin plays an important role in vascular endothelial function in obese adolescents.