Expression Of Synthesis-related Genes Research Articles

The starch excess and key genes underlying citrus leaf chlorosis by rootstock-scion incompatibility

Leaf chlorosis caused by rootstock-scion incompatibility in citrus orchard badly affects fruit yield and quality. Starch excess and its key genes underlying citrus leaf chlorosis in incompatible graft remained unknown. Here, using created model incompatible/ compatible rootstock-scion combinations, we investigated starch content and distribution in 116 various chlorotic leaves of incompatible graft, and characterized the relationship between leaf chlorosis and starch accumulation. Further, we identified starch metabolism-related gene families by genome-wide analysis of pomelo genome, and performed comparative transcriptomic analysis on leaves. A total of nine key differentially expressed genes of starch metabolism were validated. Among them, seven starch synthesis-related genes were significantly upregulated, and two starch degradation-related genes, CgBAM4 and CgBAM6, were significantly downregulated. Meanwhile, the relative expression of synthesis-related genes was positively correlated with starch accumulation and leaf chlorosis. Using transient overexpression and VIGS experiments in pomelo, we confirmed the function of CgGBSS2, which was the only amylose synthesis-related key gene with the most significantly upregulated expression level. We proposed a working model to illustrate the regulatory network of starch excess accumulation involving in citrus leaf chlorosis of incompatible graft in the end. This study provides insights into the molecular mechanism underlying leaf chlorosis process in rootstock-scion incompatibility.

Supplementation of Chlorogenic Acid Alleviates the Effects of H2O2-Induced Oxidative Stress on Laying Performance, Egg Quality, Antioxidant Capacity, Hepatic Inflammation, Mitochondrial Dysfunction, and Lipid Accumulation in Laying Hens

This research examined the impact of chlorogenic acid (CGA) on laying performance, antioxidant capacity, egg quality, hepatic inflammation, mitochondrial function, and lipid metabolism in hens subjected to hydrogen peroxide (H2O2)-induced oxidative stress (OS). Three hundred sixty healthy 43-wk-old Hy-Line brown hens were randomly assigned to six treatments: a basal diet + 0 (control and H2O2), 600 (600 mg/kg CGA and 600 mg/kg CGA + H2O2), and 800 (800 mg/kg CGA and 800 mg/kg CGA + H2O2) mg/kg CGA for 84 d. On the 64th and 78th days of the trial, hens in groups H2O2, 600 mg/kg CGA + H2O2, and 800 mg/kg CGA + H2O2 were injected intraperitoneally with 10% H2O2. The results demonstrated that 600 and 800 mg/kg CGA significantly improved the egg production rate (EPR) and egg quality and reduced lipid peroxidation compared to the control group. The 800 mg/kg CGA showed greater improvements in the EPR and average egg weight (AEW) compared to the 600 mg/kg dose. Conversely, H2O2 exposure significantly decreased the EPR, AEW, and egg quality and increased feed conversion rate and average daily feed intake. H2O2 exposure significantly decreased serum T-AOC and increased serum MDA levels while reducing hepatic T-SOD, GSH-Px, and CAT activities. Meanwhile, H2O2 exposure significantly elevated liver reactive oxygen species levels, pathological damage, and NF-κB, TNFα, and IL-1β gene expression. Additionally, H2O2 treatment disrupted hepatocyte mitochondrial structure and significantly increased the expression of VDAC1 protein, and IP3R, GRP75, MCU, Fis1, and MFF genes, while downregulating the expression of MFN2 protein and PGC1α gene. Oil Red O staining demonstrated that H2O2 induced significant lipid accumulation in hepatocytes. Concurrently, H2O2 significantly increased serum triglycerides, total cholesterol, and liver triglycerides levels while decreasing serum hepatic lipase activity. This was primarily attributed to the significant upregulation of liver SREBP1, FASN, and ACC genes and the downregulation of the liver CPT1 gene induced by H2O2. Furthermore, CGA pretreatment effectively prevented the degeneration in laying performance and egg quality, as well as OS, liver inflammation, pathological damage, and mitochondrial dysfunction induced by H2O2. CGA inhibited H2O2-induced hepatic lipid accumulation by upregulating fatty acid oxidation-related gene expression and downregulating fatty acid synthesis-related gene expression. These findings indicate that the dietary addition of 800 mg/kg of CGA is the optimum supplementation dose. CGA can enhance laying performance and egg quality while alleviating OS, hepatic inflammation, mitochondrial dysfunction, and lipid accumulation in H2O2-challenged laying hens.

Bound phenolics extracts of jujube peel relieve cadmium-induced toxicity by reducing lipid accumulation of Caenorhabditis elegans.

To investigate the effect of bound phenolics extracts (BPEs) of jujube peel on relieving cadmium (Cd)-induced toxicity and its mechanism, the behavioral deficits, lipid accumulation, and fatty acid synthesis-related gene expression in Caenorhabditis elegans in Cd exposure group and BPEs improvement groups were determined and compared. The results showed that BPEs significantly improved Cd-induced behavioral deficits in C. elegans, and no significant differences could be found in low-dose (12.5µg/mL) and high-dose (100µg/mL) BPEs improvement groups. The treatment of BPEs effectively improved intestinal injury and lipofuscin and lipid accumulation. Especially, oil red O staining intensity in C. elegans treated with BPEs at 50µg/mL was reduced by 12.60%. BPEs significantly controlled the increase in content of C16:0, C16:1, C18:0, C18:1, and C18:2 induced by Cd by regulating the lipid accumulation in Escherichia coli OP50. Cd exposure induced lipid accumulation in C. elegans by upregulating oleic acid synthesis-related gene expression in E. coli OP50. Furthermore, BPEs treatment significantly downregulated the fatty acid synthesis-related gene expression in C. elegans and E. coli OP50. This research could reveal the mechanism of BPEs of jujube peel in relieving Cd-induced toxicity and provide a theoretical basis for the development of functional foods rich in polyphenols. PRACTICAL APPLICATION: Jujube peel, a by-product of jujube processing, is usually discarded due to its coarse texture. However, jujube peel has been proven to possess abundant polyphenols, polysaccharides, and cyclic adenosine phosphate. In addition, in our previous research, bound phenolics extracts (BPEs) of jujube peel were found to perform better in lowering lipid accumulation than that of free phenolics extracts. This study further investigate the effect of BPEs of jujube peel on relieving Cd-induced toxicity and its mechanism on the base of our previous research. It could realize the comprehensive utilization of by-products of jujube processing.

Nlrp6 overexpression inhibits lipid synthesis to suppress proliferation of hepatocellular carcinoma cells by regulating the AMPK-Srebp1c axis

To investigate the mechanism of Nlrp6 for regulating hepatocellular carcinoma (HCC) progression in light of lipid synthesis regulation. Nlrp6 expression level in HCC tissues of different pathological grades was investigated using RNA-seq data from The Cancer Genome Atlas (TCGA) database, and its correlation with the patients' survival was analyzed with Kaplan-Meier survival analysis. HepG2 cells with adenovirus-mediated Nlrp6 overexpression or knockdown were treated with palmitic acid (PA), and the changes in lipid deposition and cell proliferation were evaluated using Oil Red O staining, CCK-8 assay, EdU staining, and colony formation assay. RT-qPCR and Western blotting were used to detect the changes in expression of lipid synthesis-related genes and the proteins in the AMPK-Srebp1c axis. In a mouse model of hepatic steatosis established in liver-specific Nlrp6 knockout mice by high-fat diet feeding for 24 weeks, liver fibrosis was examined with histological staining, and the changes in expressions of HCC markers and the AMPK-Srebp1c signaling pathway were detected. Nlrp6 expression was significantly reduced in HCC tissues with negative correlations with the pathological grades and the patients' survival (P < 0.0001). In HepG2 cells, Nlrp6 overexpression significantly inhibited lipid deposition and cell proliferation, whereas Nlrp6 knockdown produced the opposite effects. Nlrp6 overexpression strongly suppressed the expression of lipid synthesis-related genes, promoted AMPK phosphorylation, and inhibited Srebp1c expression. The mice with liver-specific Nlrp6 knockout and high-fat feeding showed increased hepatic steatosis, collagen deposition, and AFP expression with reduced AMPK phosphorylation and increased Srebp1c expression. Nlrp6 overexpression inhibits lipid synthesis in HCC cells by regulating the AMPK-Srebp1c axis, which might be a key pathway for suppressing HCC cell proliferation.

Circadian Clock Disruption and Growth of Kidney Cysts in Autosomal Dominant Polycystic Kidney Disease.

Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in the PKD1 and PKD2 genes, and often progresses to kidney failure. ADPKD progression is not uniform among patients, suggesting that factors secondary to the PKD1/2 gene mutation could regulate the rate of disease progression. Here we tested the effect of circadian clock disruption on ADPKD progression. Circadian rhythms are regulated by cell-autonomous circadian clocks composed of clock proteins. BMAL1 is a core constituent of the circadian clock. To disrupt the circadian clock, we deleted Bmal1 gene in the renal collecting ducts of the Pkd1RC/RC (RC/RC) mouse model of ADPKD (RC/RC;Bmal1f/f;Pkhd1cre, called DKO mice), and in Pkd1 knockout mouse inner medullary collecting duct cells (Pkd1Bmal1KO mIMCD3 cells). Only male mice were used. Human nephrectomy ADPKD kidneys showed altered clock gene expression when compared to normal control human kidneys. When compared to RC/RC kidneys, DKO kidneys showed significantly altered clock gene expression, increased cyst growth, cell proliferation, apoptosis and fibrosis. DKO kidneys also showed increased lipogenesis and cholesterol synthesis-related gene expression, and increased tissue triglyceride levels compared to RC/RC kidneys. Similarly, in vitro, Pkd1Bmal1KO cells showed altered clock genes, increased lipogenesis and cholesterol synthesis-related genes, and reduced fatty-acid oxidation-related gene expression compared to Pkd1KO cells. The Pkd1Bmal1KO cells showed increased cell proliferation compared to Pkd1KO cells, which was rescued by pharmacological inhibition of lipogenesis. Renal collecting duct specific Bmal1 gene deletion disrupted the circadian clock and triggered accelerated ADPKD progression by altering lipid metabolism-related gene expression.

Continuous Theta Burst Stimulation Inhibits Oxidative Stress-Induced Inflammation and Autophagy in Hippocampal Neurons by Activating Glutathione Synthesis Pathway, Improving Cognitive Impairment in Sleep-Deprived Mice.

Sleep deprivation (SD) has been reported to have a negative impact on cognitive function. Continuous theta burst stimulation (cTBS) shows certain effects in improving sleep and neurological diseases, and its molecular or cellular role in SD-induced cognition impairment still need further exploration. In this study, C57BL/6 mice were subjected to 48h of SD and cTBS treatment, and cTBS treatment significantly improved SD-triggered impairment of spatial learning and memory abilities in mice. Additionally, cTBS reduced malondialdehyde levels, increased superoxide dismutase activities, and inhibited the production of inflammatory cytokines, alleviating oxidative stress and inflammation levels in hippocampal tissues of SD model mice. cTBS decreased LC3II/LC3I ratio, Beclin1 protein levels, and LC3B puncta intensity, and elevated p62 protein levels to suppress excessive autophagy in hippocampal tissues of SD-stimulated mice. Then, we proved that inhibiting oxidative stress alleviated inflammation, autophagy, and death of hippocampal neuron cells through an in vitro cellular model for oxidative stress, and cTBS treatment promoted the production of glutathione (GSH), the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and the mRNA expression of GSH synthesis-related genes to enhance antioxidant capacity in hippocampal tissues of SD mice. An Nrf2 inhibitor ML385 or a GSH synthesis inhibitor BSO reversed the alleviating effects of cTBS treatment on oxidative stress-associated damage of hippocampal tissues and cognitive impairment in SD model mice. Altogether, our study demonstrated that cTBS mitigates oxidative stress-associated inflammation and autophagy through activating the Nrf2-mediated GSH synthesis pathway, improving cognitive impairment in SD mice.

Chlorophyll and Carotenoid Metabolism Varies with Growth Temperatures among Tea Genotypes with Different Leaf Colors in Camellia sinensis

The phenotype of albino tea plants (ATPs) is significantly influenced by temperature regimes and light conditions, which alter certain components of the tea leaves leading to corresponding phenotypic changes. However, the regulatory mechanism of temperature-dependent changes in photosynthetic pigment contents and the resultant leaf colors remain unclear. Here, we examined the chloroplast microstructure, shoot phenotype, photosynthetic pigment content, and the expression of pigment synthesis-related genes in three tea genotypes with different leaf colors under different temperature conditions. The electron microscopy results revealed that all varieties experienced the most severe chloroplast damage at 15 °C, particularly in albino cultivar Baiye 1 (BY), where chloroplast basal lamellae were loosely arranged, and some chloroplasts were even empty. In contrast, the chloroplast basal lamellae at 35 °C and 25 °C were neatly arranged and well-developed, outperforming those observed at 20 °C and 15 °C. Chlorophyll and carotenoid measurements revealed a significant reduction in chlorophyll content under low temperature treatment, peaking at ambient temperature followed by high temperatures. Interestingly, BY showed remarkable tolerance to high temperatures, maintaining relatively high chlorophyll content, indicating its sensitivity primarily to low temperatures. Furthermore, the trends in gene expression related to chlorophyll and carotenoid metabolism were largely consistent with the pigment content. Correlation analysis identified key genes responsible for temperature-induced changes in these pigments, suggesting that changes in their expression likely contribute to temperature-dependent leaf color variations.

High-sucrose diet induces abnormalities in lipid metabolism through gut microbiome dysbiosis linked to five metronidazole-suppressed bacteria

Public attention to the correlation between excessive sucrose consumption and metabolic syndrome has facilitated research on its underlying mechanisms. Recent studies have newly identified the intestine, rather than the liver, as the predominant site of dietary fructose metabolism, which corrects the previous concepts and links the promotion of fatty liver and hyperlipidemia to gut microbiota dysbiosis, although the specific mode of action remains unclear. Here, we used microbiota suppression to identify the causative bacteria. Male Wistar rats were fed a starch or high-sucrose diet and orally administered two independent antibiotic treatments for four weeks. Metronidazole, neomycin, ampicillin, vancomycin, and their mixture were used to explore highly sucrose-responsive bacteria. Metronidazole and the mixture decreased or showed a tendency to decrease high-sucrose diet-induced increases in liver weight, plasma triglyceride levels, and fatty acid synthesis-related gene expression (ATP citrate lyase, fatty acid synthase, and malic enzyme). To further investigate the ability of metronidazole to ameliorate high-sucrose diet-induced abnormalities in lipid metabolism, three nitroimidazole antibiotics (metronidazole, tinidazole, and ornidazole) were used. Only metronidazole reduced the liver weight and decreased plasma triglyceride levels on a high-sucrose diet. Among the high-sucrose diet induction effects, five bacteria suppressed by metronidazole were screened, belonging to the family Rikenellaceae, genera Bacteroides, Blautia, and Dorea, and species Eubacterium dolichum. Overall, suppression of the gut microbiota by metronidazole-specific action, rather than the nitroreductase activity of tinidazole and ornidazole, was responsible for the amelioration of high-sucrose diet-induced fatty liver and hypertriglyceridemia. Five causative bacteria were identified in this study.

Investigation of the physiological effects of uridine on Nile Tilapia (Oreochromis niloticus)

Uridine, an essential nucleoside involved in various physiological and biochemical processes, has been shown to influence hepatic fat accumulation. However, its broader physiological roles in aquaculture species like Nile tilapia remain underexplored. This study aimed to systematically assess the effects of uridine on Nile tilapia physiology. Nile tilapia (3.58 ± 0.02 g) were fed with different levels (0, 1, and 4 g/kg) of uridine for 10 weeks. The supplementation with 4 g/kg uridine significantly increased the carcass ratio and total protein of whole fish by 4.18 % and 4.08 %, respectively, and reduced the viscerosomatic index and total lipid of whole fish by 12.76 % and 20.48 %, respectively. Supplementation with 4 g/kg uridine increased the expression of protein synthesis genes. The supplementation of uridine suppressed the expression of fatty acid synthesis genes and promoted the expression of lipolysis-related genes by the activation of AMP-activated protein kinase (AMPK). This activation led to a significant decrease in both liver and serum triglyceride levels. The administration of 4 g/kg uridine significantly reduced hepatic cholesterol levels by inhibiting the expression of cholesterol synthesis-related genes. Additionally, 4 g/kg uridine notably augmented the liver's antioxidant capacity, thereby promoting the hepatic health. Furthermore, addition of uridine elevated the intestinal villi height, improved intestinal barrier integrity, and reduced intestinal inflammation response. Therefore, this study suggested that dietary supplementation of uridine can promote protein deposition and improve hepatic and intestinal health in Nile tilapia.

Circadian clock disruption and growth of kidney cysts in autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in the PKD1 and PKD2 genes, and often progresses to kidney failure. ADPKD progression is not uniform among patients, suggesting that factors secondary to the PKD1/2 gene mutation could regulate the rate of disease progression. Here we tested the effect of circadian clock disruption on ADPKD progression. Circadian rhythms are regulated by cell-autonomous circadian clocks composed of clock proteins. BMAL1 is a core constituent of the circadian clock. To disrupt the circadian clock, we deleted Bmal1 gene in the renal collecting ducts of the Pkd1 RC/RC (RC/RC) mouse model of ADPKD (RC/RC; Bmal1 f/f ; Pkhd1 cre , called DKO mice), and in Pkd1 knockout mouse inner medullary collecting duct cells ( Pkd1Bmal1 KO mIMCD3 cells). Only male mice were used. Human nephrectomy ADPKD kidneys and Pkd1 KO mIMCD3 cells showed reduced Bmal1 gene expression compared to normal controls. When compared to RC/RC kidneys, DKO kidneys showed significantly altered clock gene expression, increased cyst growth, cell proliferation, apoptosis and fibrosis. DKO kidneys also showed increased lipogenesis and cholesterol synthesis-related gene expression, and increased tissue triglyceride levels compared to RC/RC kidneys. Similarly, in vitro, Pkd1Bmal1 KO cells showed altered clock genes, increased lipogenesis and cholesterol synthesis-related genes, and reduced fatty-acid oxidation-related gene expression compared to Pkd1KO cells. The Pkd1Bmal1 KO cells showed increased cell proliferation compared to Pkd1KO cells, which was rescued by pharmacological inhibition of lipogenesis. Renal collecting duct specific Bmal1 gene deletion disrupts the circadian clock and triggers accelerated ADPKD progression by altering lipid metabolism-related gene expression. Lack of BMAL1, a circadian clock protein in renal collecting ducts disrupted the clock and increased cyst growth and fibrosis in an ADPKD mouse model.BMAL1 gene deletion increased cell proliferation by increasing lipogenesis in kidney cells.Thus, circadian clock disruption could be a risk factor for accelerated disease progression in patients with ADPKD.

RNA-seq reveals the gene expression in patterns in Populus × euramericana 'Neva' plantation under different precision water and fertilizer-intensive management.

Populus spp. is a crucial fast-growing and productive tree species extensively cultivated in the mid-latitude plains of the world. However, the impact of intensive cultivation management on gene expression in plantation remains largely unexplored. Precision water and fertilizer-intensive management substantially increased key enzyme activities of nitrogen transport, assimilation, and photosynthesis (1.12-2.63 times than CK) in Populus × euramericana 'Neva' plantation. Meanwhile, this management approach had a significant regulatory effect on the gene expression of poplar plantations. 1554 differential expression genes (DEGs)were identified in drip irrigation (ND) compared with conventional irrigation. Relative to ND, 2761-4116 DEGs, predominantly up-regulated, were identified under three drip fertilization combinations, among which 202 DEGs were mainly regulated by fertilization. Moreover, drip irrigation reduced the expression of cell wall synthesis-related genes to reduce unnecessary water transport. Precision drip and fertilizer-intensive management promotes the synergistic regulation of carbon and nitrogen metabolism and up-regulates the expression of major genes in nitrogen transport and assimilation processes (5 DEGs), photosynthesis (15 DEGs), and plant hormone signal transduction (11 DEGs). The incorporation of trace elements further enhanced the up-regulation of secondary metabolic process genes. In addition, the co-expression network identified nine hub genes regulated by precision water and fertilizer-intensive management, suggesting a pivotal role in regulating the growth of poplar. Precision water and fertilizer-intensive management demonstrated the ability to regulate the expression of key genes and transcription factor genes involved in carbon and nitrogen metabolism pathways, plant hormone signal transduction, and enhance the activity of key enzymes involved in related processes. This regulation facilitated nitrogen absorption and utilization, and photosynthetic abilities such as light capture, light transport, and electron transport, which faintly synergistically regulate the growth of poplar plantations. These results provide a reference for proposing highly efficient precision intensive management to optimize the expression of target genes.

Testosterone-promoting effects of Trichosanthes kirilowii-derived peptides on TM3 cells

Bioactive peptides have been shown to have a variety of functions, but very few studies have tapped into their promotional effects and mechanisms on testosterone synthesis. The aim of this study was to investigate the effect of Trichosanthes kirilowii-derived peptide on testosterone synthesis in TM3 cells and its mechanism of action. In this study, we found that the peptide purification fraction TSH1-3 and the peptide VTPVGSPR from Trichosanthes kirilowii seed hydrolysate (TSH) significantly promoted the synthesis of testosterone, dihydrotestosterone, free testosterone, and androstenedione in TM3. Furthermore, TSH1-3 regulates the expression of testosterone synthesis-related genes and proteins StAR, TSPO, CYP11A1, and 3β-HSD in a dose-dependent manner. In addition, given the strong link between mitochondrial biogenesis and testosterone synthesis, we further found that both TSH1-3 and VTPVGSPR promoted mtDNA production and up-regulated the expression of genes important for mitochondrial biogenesis, PGC-1α, TFAM, TFB1M, TFB2M, NRF1 and NRF2. In short, this study demonstrates that TSH can be used as a potential dietary supplement to promote sex hormone production and regulate physical health.

Lotus seed protein ameliorates hepatic lipid metabolic disorders in high-fat diet-fed mice via activating the PPARα signaling pathway

Obesity, one of the prevalent chronic diseases globally, is a serious threat to human health. Dietary natural compounds intervention is an effective means to alleviate obesity. The objective of this study was to investigate the potential protective role of lotus seed protein (LSP) against obesity. The results of amino acid composition analysis indicated that LSP possessed a well-balanced distribution of amino acids and was rich in branched-chain amino acids (BCAAs). Meanwhile, LSP exhibited better ABTS radical scavenging, DPPH radical scavenging, hydroxyl radical scavenging, and Fe2+ chelating ability in vitro. In vivo, LSP intervention remarkably alleviated body weight gain, organ index gain, dyslipidemia, and hepatic lipid deposition in high-fat diet (HFD)-fed mice. Meanwhile, LSP enhanced hepatic antioxidant enzyme activities (superoxide dismutase (SOD) and catalase (CAT)) and decreased malondialdehyde (MDA) levels, subsequently alleviated liver injury. In addition, LSP intervention significantly improved insulin sensitivity and glucose tolerance in obese mice, thereby alleviating hyperglycemia and insulin resistance. At the molecular level, LSP intervention up-regulated the mRNA and protein expression of fatty acid oxidation-related genes (FATP1, CPT-1a, ACOX1) and down-regulated the mRNA and protein expression of lipid synthesis-related genes (SREBP-1c, ACC, SCD-1, FASN) by activating the PPARα signaling pathway, thereby promoting hepatic fatty acid oxidation and reducing lipogenesis. These results demonstrate that LSP has the potential as a dietary supplementation to prevent and ameliorate obesity.

PF-05231023 reduces lipid deposition in apolipoprotein E-deficient mice by inhibiting the expression of lipid synthesis genes.

Fibroblast growth factor 21 (FGF21) is a peptide hormone that is primarily expressed and secreted by the liver. The hormone is crucial for regulation of glucose homeostasis, lipid metabolism, and energy balance. Compared with natural FGF21, FGF21 analogs have become drug candidates for the treatment of cardiovascular and metabolic diseases owing to their long half-life and greater stability in vitro. Apolipoprotein E (Apoe)-knockout (Apoe -/-) mice exhibit progressive disruptions in lipid metabolism in vivo and develop further atherosclerosis pathological features owing to Apoe deletion. Therefore, this study used an Apoe -/- mouse model to investigate the effects of a long-acting FGF21 analog (PF-05231023) on lipid metabolism and related parameters. Eighteen Apoe -/- female mice were fed a Western diet equivalent for 12 weeks, and then randomly assigned to intraperitoneally receive either physiological saline (the control group) or 10 mg/kg PF-05231023 (the treatment group) three times a week for seven consecutive weeks. Body composition, glucose tolerance, blood and liver cholesterol, triglyceride levels, liver vacuolization levels, peri-ovarian white adipocyte hypertrophy, aortic atherosclerotic plaque formation, and the expression of genes related to lipid metabolism in adipose tissue were subsequently assessed before and after treatment. The aortic atherosclerotic plaque area was reduced in mice in the PF-05231023 treatment group compared with that in the saline group. Although the effect of PF-05231023 on the plasma biochemical indexes of mice was small, it significantly reduced lipid levels and lipid droplet accumulation in the liver, and reduced adipocyte hypertrophy in white adipose tissue. Transcriptome analysis of adipose tissue showed that PF-05231023 treatment downregulated the expression of lipid synthesis-related genes and inhibited the sterol regulatory element binding transcription factor 1 gene, thereby improving lipid deposition. PF-05231023 effectively improved the lipid metabolism of Apoe -/- mice, demonstrating an anti-atherosclerotic effect and providing a scientific basis and experimental foundation for the clinical treatment of cardiovascular diseases by using long-acting FGF21 analogs.

Free fatty acids induce bile acids overproduction and oxidative damage of bovine hepatocytes via inhibiting FXR/SHP signaling

Hepatic oxidative injury induced by free fatty acids (FFA) and metabolic disorders of bile acids (BA) increase the risk of metabolic diseases in dairy cows during perinatal period. However, the effects of FFA on BA metabolism remained poorly understood. In present study, high concentrations of FFA caused cell impairment, oxidative stress and BA overproduction. FFA treatment increased the expression of BA synthesis-related genes [cholesterol 7a-hydroxylase (CYP7A1), hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 7, sterol 12α-hydroxylase, sterol 27-hydroxylase and oxysterol 7α-hydroxylase], whereas reduced BA exportation gene (ATP binding cassette subfamily C member 1) and inhibited farnesoid X receptor/small heterodimer partner (FXR/SHP) pathway in bovine hepatocytes. Knockdown of nuclear receptor subfamily 1 group H member 4 (NR1H4) worsened FFA-caused oxidative damage and BA production, whereas overexpression NR1H4 ameliorated FFA-induced BA production and cell oxidative damage. Besides, reducing BA synthesis through knockdown of CYP7A1 can alleviate oxidative stress and hepatocytes impairment caused by FFA. In summary, these data demonstrated that regulation of FXR/SHP-mediated BA metabolism may be a promising target in improving hepatic oxidative injury of dairy cows during high levels of FFA challenges.

Suitable dietary phospholipids improve lipid deposition, but excessive dietary phospholipids disorder lipid metabolism in juvenile leopard coral grouper (Plectropomus leopardus)

Limited investigation has been available on the effects of dietary phospholipids in leopard coral grouper (Plectropomus leopardus), hindering its potential for aquaculture. This study was intended to investigate the impact of various levels (05 %) of dietary soy lecithin (SL) on juvenile P. leopardus over a 9-week feeding trial. Results indicated that dietary inclusion of 23 % SL enhanced the lipid content in liver, muscle, and whole-body. The fatty acid composition of muscle strongly reflected the dietary fatty acid profile. Furthermore, dietary inclusion of 3 % SL enhanced the activities of hepatic lipid synthesis enzymes [fatty acid synthase (FAS), glucose-6-phosphate dehydrogenase (G6PD)] and lipolytic enzymes [hormone-sensitive lipase (HSL), carnitine palmitoyltransferase-1 (CPT-1)]. Additionally, the inclusion of 23 % SL upregulated the relative expression of lipid synthesis-related genes [fas, sterol regulatory element binding transcription factor 1 (srebp1)] and lipid catabolism-related genes [hsl, cpt-1, and lipoprotein lipase (lpl)] in muscle. However, increasing dietary SL levels up to 45 % led to a reduction in muscle and whole-body lipid content, and an enhance in hepatic lipid content and hepatocyte vacuolization. Moreover, dietary inclusion of 5 % SL downregulated the relative expressions of hepatic lipid synthesis-related genes (g6pd and srebp1) and lipid catabolism-related genes (lpl and hsl). Overall, including 23 % SL in the diet improved lipid metabolism and thereby enhanced lipid deposition in juvenile P. leopardus, but excessive SL (45 %) disrupted lipid metabolism.

CELLULOSE SYNTHASE-LIKE C proteins modulate cell wall establishment during ethylene-mediated root growth inhibition in rice.

The cell wall shapes plant cell morphogenesis and affects the plasticity of organ growth. However, the way in which cell wall establishment is regulated by ethylene remains largely elusive. Here, by analyzing cell wall patterns, cell wall composition and gene expression in rice (Oryza sativa, L.) roots, we found that ethylene induces cell wall thickening and the expression of cell wall synthesis-related genes, including CELLULOSE SYNTHASE-LIKE C1, 2, 7, 9, 10 (OsCSLC1, 2, 7, 9, 10) and CELLULOSE SYNTHASE A3, 4, 7, 9 (OsCESA3, 4, 7, 9). Overexpression and mutant analyses revealed that OsCSLC2 and its homologs function in ethylene-mediated induction of xyloglucan biosynthesis mainly in the cell wall of root epidermal cells. Moreover, OsCESA-catalyzed cellulose deposition in the cell wall was enhanced by ethylene. OsCSLC-mediated xyloglucan biosynthesis likely plays an important role in restricting cell wall extension and cell elongation during the ethylene response in rice roots. Genetically, OsCSLC2 acts downstream of ETHYLENE-INSENSITIVE3-LIKE1 (OsEIL1)-mediated ethylene signaling, and OsCSLC1, 2, 7, 9 are directly activated by OsEIL1. Furthermore, the auxin signaling pathway is synergistically involved in these regulatory processes. These findings link plant hormone signaling with cell wall establishment, broadening our understanding of root growth plasticity in rice and other crops.

A Characterization and Functional Analysis of Peroxisome Proliferator-Activated Receptor Gamma Splicing Variants in the Buffalo Mammary Gland.

Peroxisome proliferator-activated receptor γ (PPARG) has various splicing variants and plays essential roles in the regulation of adipocyte differentiation and lipogenesis. However, little is known about the expression pattern and effect of the PPARG on milk fat synthesis in the buffalo mammary gland. In this study, we found that only PPARG-X17 and PPARG-X21 of the splicing variant were expressed in the buffalo mammary gland. Amino acid sequence characterization showed that the proteins encoded by PPARG-X17 and PPARG-X21 are endonuclear non-secreted hydrophilic proteins. Protein domain prediction found that only the PPARG-X21-encoded protein had PPAR ligand-binding domains (NR_LBD_PPAR), which may lead to functional differences between the two splices. RNA interference (RNAi) and the overexpression of PPARG-X17 and PPARG-X21 in buffalo mammary epithelial cells (BMECs) were performed. Results showed that the expression of fatty acid synthesis-related genes (ACACA, CD36, ACSL1, GPAT, AGPAT6, DGAT1) was significantly modified (p < 0.05) by the RNAi and overexpression of PPARG-X17 and PPARG-X21. All kinds of FAs detected in this study were significantly decreased (p < 0.05) after RNAi of PPARG-X17 or PPARG-X21. Overexpression of PPARG-X17 or PPARG-X21 significantly decreased (p < 0.05) the SFA content, while significantly increased (p < 0.05) the UFA, especially the MUFA in the BMECs. In conclusion, there are two PPARG splicing variants expressed in the BMECs that can regulate FA synthesis by altering the expression of diverse fatty acid synthesis-related genes. This study revealed the expression characteristics and functions of the PPARG gene in buffalo mammary glands and provided a reference for further understanding of fat synthesis in buffalo milk.

Anethum graveolens L. restores expression of free fatty acid synthesis-related genes in high fat induced-HepG2 cells

IntroductionThe ethanolic extract of Anethum graveolens (dill) and its major constituents, chlorogenic acid (CGA) and ellagic acid (EA), were investigated for hepatoprotective effects in a HepG2 cell fatty liver model. MethodsHepG2 cells were induced with a combination of oleic (1mM OA) and palmitic (1mM PA) acids and treated with either 10 µM fenofibrate, 1-10 µg/mL CGA or EA, 60-360 µg/mL A. graveolens extract, or left untreated (n=4-5 per group). After 48 hours, cell medium and cells were collected for alanine transaminase (ALT), aspartate transaminase (AST), reactive oxygen species (ROS), and fatty acid accumulation assays. The mRNA and protein expression levels of free fatty acid (FFA) synthetic pathway-related genes were determined using reverse transcription/real-time polymerase chain reaction and Western blotting analysis, respectively. ResultsHepG2 cells treated with OA and PA showed increased ALT, AST, and ROS levels, fatty acid accumulation, and modified mRNA and protein expression of PPAR, SREBP1, ACC, ACOX, FAS, SCD1, and HMGCR fatty acid synthesis-related genes. The CGA, EA, and A. graveolens extract showed hepatoprotective activities in OA and PA-induced HepG2 cells by preventing fatty acid accumulation and restoring mRNA and protein expression levels of the fatty acid synthesis-related genes to control levels, with comparable efficacy to the standard anti-lipidemic drug, fenofibrate. Furthermore, CGA, EA, and A. graveolens extract did not increase ALT and ROS levels in HepG2 cells, in contrast to fenofibrate. ConclusionA. graveolens extract, CGA, and EA are good candidates for development as preventive health supplements for fatty liver disease therapy.

Integrating GC-MS and comparative transcriptome analysis reveals that TsERF66 promotes the biosynthesis of caryophyllene in Toona sinensis tender leaves.

The strong aromatic characteristics of the tender leaves of Toona sinensis determine their quality and economic value. Here, GC-MS analysis revealed that caryophyllene is a key volatile compound in the tender leaves of two different T. sinensis varieties, however, the transcriptional mechanisms controlling its gene expression are unknown. Comparative transcriptome analysis revealed significant enrichment of terpenoid synthesis pathway genes, suggesting that the regulation of terpenoid synthesis-related gene expression is an important factor leading to differences in aroma between the two varieties. Further analysis of expression levels and genetic evolution revealed that TsTPS18 is a caryophyllene synthase, which was confirmed by transient overexpression in T. sinensis and Nicotiana benthamiana leaves. Furthermore, we screened an AP2/ERF transcriptional factor ERF-IX member, TsERF66, for the potential regulation of caryophyllene synthesis. The TsERF66 had a similar expression trend to that of TsTPS18 and was highly expressed in high-aroma varieties and tender leaves. Exogenous spraying of MeJA also induced the expression of TsERF66 and TsTPS18 and promoted the biosynthesis of caryophyllene. Transient overexpression of TsERF66 in T. sinensis significantly promoted TsTPS18 expression and caryophyllene biosynthesis. Our results showed that TsERF66 promoted the expression of TsTPS18 and the biosynthesis of caryophyllene in T. sinensis leaves, providing a strategy for improving the aroma of tender leaves.