IN VIVO
·
2024
·Vol. 38
·期 3
·1133-1142
·
IF 1.8
LONGJIE XU,LILI HOU,CHUN CAO,XIAOHUA LI
Background/Aim: Cancer-induced bone pain (CIBP) is one of the most common symptoms of bone metastasis of tumor cells. The hypothalamus may play a pivotal role in the regulation of CIBP. However, little is known about the exact mechanisms. Materials and Methods: First, we established a CIBP model to explore the relationship among hypothalamic ghrelin, NPY and CIBP. Then, we exogenously administered NPY and NPY receptor antagonists to investigate whether hypothalamic NPY exerted an antinociceptive effect through binding to NPY receptors. Finally, we exogenously administered ghrelin to investigate whether ghrelin alleviated CIBP by inducing the production of hypothalamic NPY through the AMPK-mTOR pathway. Body weight, food intake and behavioral indicators of CIBP were measured every 3 days. Hypothalamic ghrelin, NPY and the AMPK-mTOR pathway were also measured. Results: The expression of hypothalamic ghrelin and NPY was simultaneously decreased in cancer-bearing rats, which was accompanied by CIBP. Intracerebroventricular (i.c.v.) administration of NPY significantly alleviated CIBP in the short term. The antinociceptive effect of NPY was reversed with the i.c.v. administration of the Y1R and Y2R antagonists. The administration of ghrelin activated the AMPK-mTOR pathway and induced hypothalamic NPY production to alleviate CIBP. This effect of ghrelin on NPY and antinociception was reversed with the administration of a GHS-R1α antagonist. Conclusion: Ghrelin could induce the production of hypothalamic NPY through the AMPK-mTOR pathway to alleviate CIBP, which can provide a novel therapeutic mechanism for CIBP.
研究领域:
神经科学
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疼痛研究
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肿瘤学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
Fishes
·
2023
·Vol. 8
·期 3
·170
·
IF 2.3
Lei Zhang,Peng Shi,Lin Zhang,Yajun Wang,Jilin Xu,Xiaojun Yan,Kai Liao
Ghrelin, glucagon-like peptide-1 (GLP-1), and peptide YY (PYY) are potent hormones mediating food intake according to the nutritional status in fish. However, limited information is available on these genes and their expression in response to nutrition in silver pomfret (Pampus argenteus). A comparison analysis revealed thatghrelinand GLP-1 were relatively conserved in marine fish. PYYa and PYYb shared a low identity and were clustered to different PYY branches.Ghrelin,pyya, andpyybmRNAs were highly expressed in the brain, whileglp-1was highly expressed in the gills and liver. TheghrelinmRNA expression was relatively high an hour post-feeding and decreased after 3 to 72 h of fasting. Theglp-1mRNA expression was increased after 6 to 24 h of fasting. ThepyyamRNA expression was increased after 72 h of fasting, while thepyybexpression remained stable during fasting. The diet with 14% lipid promoted the expressions ofglp-1,pyya, andpyyb, but inhibited theghrelinexpression. Theghrelinexpression in the intestine was increased after palmitic acid, oleic acid (OA), linoleic acid (LA), α-linolenic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) incubation. OA decreased the expression ofglp-1and increased the expression ofpyya. The expression ofpyybwas downregulated by LA, DHA, and EPA. These results suggest the importance ofghrelin,glp-1, andpyyin coordinating food intake in response to fasting, dietary lipid concentration, and fatty acids in silver pomfret.Keywords:ghrelin;glp-1;pyy;fasting;lipid content;fatty acids;silver pomfretKey Contribution:This study provides insight into howghrelin,glp-1, andpyyrespond to fasting, dietary lipid concentration, and fatty acids in silver pomfret.
研究领域:
海洋生物学
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分子生物学
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营养学
✓ 已验证
产品关联
DOI
高影响因子
FASEB JOURNAL
·
2024
·Vol. 38
·期 11
·e23681
·
IF 4.4
Shi-shi Liao,Le-le Zhang,Yi-guo Zhang,Jie Luo,Tulanisa Kadier,Ke Ding,Rong Chen,Qing-tao Meng
Ischemia–reperfusion (IR) injury is primarily characterized by the restoration of blood flow perfusion and oxygen supply to ischemic tissue and organs, but it paradoxically leads to tissue injury aggravation. IR injury is a challenging pathophysiological process that is difficult to avoid clinically and frequently occurs during organ transplantation, surgery, shock resuscitation, and other processes. The major causes of IR injury include increased levels of free radicals, calcium overload, oxidative stress, and excessive inflammatory response. Ghrelin is a newly discovered brain-intestinal peptide with anti-inflammatory and antiapoptotic effects that improve blood supply. The role and mechanism of ghrelin in intestinal ischemia–reperfusion (IIR) injury remain unclear. We hypothesized that ghrelin could attenuate IIR-induced oxidative stress and apoptosis. To investigate this, we established IIR by using a non-invasive arterial clip to clamp the root of the superior mesenteric artery (SMA) in mice. Ghrelin was injected intraperitoneally at a dose of 50 μg/kg 20 min before IIR surgery, and [D-Lys3]-GHRP-6 was injected intraperitoneally at a dose of 12 nmol/kg 20 min before ghrelin injection. We mimicked the IIR process with hypoxia-reoxygenation (HR) in Caco-2 cells, which are similar to intestinal epithelial cells in structure and biochemistry. Our results showed that ghrelin inhibited IIR/HR-induced oxidative stress and apoptosis by activating GHSR-1α. Moreover, it was found that ghrelin activated the GHSR-1α/Sirt1/FOXO1 signaling pathway. We further inhibited Sirt1 and found that Sirt1 was critical for ghrelin-mediated mitigation of IIR/HR injury. Overall, our data suggest that pretreatment with ghrelin reduces oxidative stress and apoptosis to attenuate IIR/HR injury by binding with GHSR-1α to further activate Sirt1.
研究领域:
药理学
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病理生理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Toxins
·
2021
·Vol. 13
·期 12
·874
·
IF 4.546
Quancheng Liu,Fuchang Li,Libo Huang,Wenjie Chen,Zhongyuan Li,Chunyang Wang
Fumonisin B1(FB1) is the most common food-borne mycotoxin produced by theFusariumspecies, posing a potential threat to human and animal health. Pigs are more sensitive to FB1ingested from feed compared to other farmed livestock. Enzymatic degradation is an ideal detoxification method that has attracted much attention. This study aimed to explore the functional characteristics of the carboxylesterase FumDSB in growing pigs from the perspective of brain–gut regulation. A total of 24 growing pigs were divided into three groups. The control group was fed a basal diet, the FB1group was supplemented with FB1at 5 mg/kg feed, and the FumDSB group received added FumDSB based on the diet of the FB1group. After 35 days of animal trials, samples from the hypothalamus and jejunum were analyzed through HE staining, qRT-PCR and immunohistochemistry. The results demonstrated that the ingestion of FB1can reduce the feed intake and weight gain of growing pigs, indicating that several appetite-related brain-gut peptides (including NPY, PYY, ghrelin and obestatin, etc.) play important roles in the anorexia response induced by FB1. After adding FumDSB as detoxifying enzymes, however, the anorexia effects of FB1were alleviated, and the expression and distribution of the corresponding brain-gut peptides exhibited a certain degree of regulation. In conclusion, the addition of FumDSB can reduce the anorexia effects of FB1by regulating several brain-gut peptides in both the hypothalamus and the jejunum of growing pigs.Keywords:fumonisin B1;carboxylesterase FumDSB;hypothalamus;jejunum;brain-gut peptide;ghrelin;obestatin;growing pigsKey Contribution:In this study, the effects of carboxylesterase FumDSB on appetite-related brain-gut peptides in both the hypothalamus and the jejunum of growing pigs were evaluated; next, the mechanism and safety of FumDSB was explored from the perspective of brain–gut regulation, which provided a research basis for the application of FumDSB in actual production.
研究领域:
兽医学
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毒理学
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分子生物学
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动物营养
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
·
2024
·
IF 7.6
Lihua Feng,Yuanyuan Lang,Leke Sun,Weihong Shi,Xiangxiang Chen,Yanan Xia,Hengyi Xu,Yang Liu
Titanium dioxide nanoparticles (TiO 2 NPs) are widely used in children’s daily necessities and foods, and their health hazards to children have attracted particular attention. Childhood is a critical time for accelerated bone growth and development. Current studies revealed that TiO 2 NPs exposure causes bone damage in juvenile rats; however, the underlying mechanism is unknown. Ghrelin is a polypeptide hormone that is considered to be a candidate factor for regulating bone growth and development. In this research, 3-week-old juvenile male rats were administered 0, 100 or 200 mg/kg TiO 2 NPs and 50 μg/kg ghrelin for 4 weeks to explore the underlying mechanism of TiO 2 NPs-induced bone damage, and the protective effect of ghrelin. Our results revealed that TiO 2 NPs resulted in decreased synthesis of bone growth-related hormones, disturbed bone metabolism, and destruction of bone structure. Further mechanism studies showed that TiO 2 NPs inhibited Wnt/β-catenin pathway, reduced collagen synthesis, inhibited chondrocyte proliferation and differentiation, promoted chondrocyte apoptosis, and inhibited endochondral osteogenesis, ultimately leading to long bone longitudinal growth retardation and osteoporosis. Ghrelin alleviated the negative effects of TiO 2 NPs-induced bone growth in juvenile rats by upregulating the Wnt/β-catenin signaling pathway. This study provided a reference for the clinical treatment of growth retardation and idiopathic short stature in juvenile children caused by environmental pollutants.
研究领域:
毒理学
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内分泌学
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儿科
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骨骼生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
·
2021
·
IF 4.698
Xixi Song,Minghui Wang,Hongchao Jiao,Jingpeng Zhao,Xiaojuan Wang,Hai Lin
Ghrelin, classically known as a central appetite-stimulating hormone, has recently been recognized to play an important role in peripheral tissue energy metabolism. In chicken, contrary to mammal, ghrelin acts as an anorexia signal, increased by fasting and further elevated after refed. In the present study, the effect of ghrelin on glucose/lipid utilization by peripheral tissues was investigated. Injection of exogenous acyl ghrelin reduced plasma triglyceride and glucose levels of chickens at both fasting and fed status. In the in vitro cultured chicken primary hepatocytes, adipocytes, and myoblasts, ghrelin suppressed glucose uptake , stimulated fatty acids uptake and oxidation , and decreased TG content. In hepatocyte, ghrelin increased the activities of LPL and HL, and upregulated the expression levels of gene ACC , CPT1 , and PPARα . Ghrelin treatment markedly increased the protein level of p-ACC, PPARγ, PGC1α, and CPT1 in hepatocytes, adipocytes and myoblasts. Inhibition of AMPK activity by Compound C had no influence on glucose uptake by hepatocyte, adipocyte, and myoblast, but further amplified the stimulated fatty acid uptake of adipocyte by ghrelin. The present result demonstrates that ghrelin facilitates the uptake and oxidation of fatty acid and cut down the utilization of glucose by the liver, muscle, and adipose tissues. The result suggests that ghrelin functions as a signal of fatty acid oxidation. The study provides a vital framework for understanding the intrinsic role of ghrelin as a crucial factor in the concerted regulation of metabolic substrate of hepatocytes, adipocytes, and myoblasts.
研究领域:
内分泌学
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代谢
·
动物生理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
GENERAL AND COMPARATIVE ENDOCRINOLOGY
·
2018
·
IF 2.564
Xixi Song,Hongchao Jiao,Jingpeng Zhao,Xiaojuan Wang,Hai Lin
Ghrelin is one of the most important appetite regulating peptides, involved in the regulation of energy homeostasis. The role of ghrelin on the appetite and fat metabolism in chickens is different from that of ghrelin in mammals. Glucocorticoids and insulin are important hormones and work differently in energy regulation of body. In this study, the effects of dexamethasone (DEX, 2.0 mg/kg BW), subcutaneous insulin injection (40 µg/kg BW), and glucose load on ghrelin secretion and expression were determined in broilers. DEX treatment increased circulating ghrelin concentration in broiler fed with either a low-energy diet (11.05 MJ/kg of metabolizable energy) or a high-energy diet (14.44 MJ/kg of metabolizable energy). The expression levels of ghrelin were increased while both ghrelin and its receptor GHS-R1a expression levels were stimulated by DEX. A single subcutaneous insulin injection (40 µg/kg BW) or oral glucose infusion (2 g/kg BW) rise circulating ghrelin level. Ghrelin expression in the proventriculus was increased by insulin treatment but unchanged by glucose load. DEX had no detectable influence on ghrelin and GHS-R1a expression in the hypohtalamus, whereas insulin suppressed their expression. In conclusion, both insulin and glucocorticoid stimulate ghrelin secretion in chickens, in contrast to mammals. Glucocorticoids evoke peripheral ghrelin/GHS-R1a system while insulin increases peripheral ghrelin expression and suppress the activation of central ghrelin/GHS-R1a system. The result suggests that ghrelin involved in the modulating network of energy homeostasis in concert with glucocorticoids and insulin.
研究领域:
动物科学
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内分泌学
·
营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2023
·Vol. 28
·期 3
·1-14
·
IF 3.4
Gui-Bo Liu,Yong-Xia Cheng,Hua-Min Li,Yong Liu,Li-Xin Sun,Qi Wu,Shang-Fu Guo,Ting-Ting Li,Chuan-Ling Dong,Ge Sun
Adipose tissue‑derived mesenchymal stem cells (ADMSCs) differentiate into cardiomyocytes and may be an ideal cell source for myocardial regenerative medicine. Ghrelin is a gastric‑secreted peptide hormone involved in the multilineage differentiation of MSCs. To the best of our knowledge, however, the role and potential downstream regulatory mechanism of ghrelin in cardiomyocyte differentiation of ADMSCs is still unknown. The mRNA and protein levels were measured by reverse transcription‑quantitative PCR and western blotting. Immunofluorescence staining was used to show the expression and cellular localization of cardiomyocyte markers and β‑catenin. RNA sequencing was used to explore the differentially expressed genes (DEGs) that regulated by ghrelin. The present study found that ghrelin promoted cardiomyocyte differentiation of ADMSCs in a concentration‑dependent manner, as shown by increased levels of cardiomyocyte markers GATA binding protein 4, α‑myosin heavy chain (α‑MHC), ISL LIM homeobox 1, NK2 homeobox 5 and troponin T2, cardiac type. Ghrelin increased β‑catenin accumulation in nucleus and decreased the protein expression of secreted frizzled‑related protein 4 (SFRP4), an inhibitor of Wnt signaling. RNA sequencing was used to determine the DEGs regulated by ghrelin. Functional enrichment showed that DEGs were more enriched in cardiomyocyte differentiation‑associated terms and Wnt pathways. Dead‑box helicase 17 (DDX17), an upregulated DEG, showed enhanced mRNA and protein expression levels following ghrelin addition. Overexpression of DDX17 promoted protein expression of cardiac‑specific markers and β‑catenin and enhanced the fluorescence intensity of α‑MHC and β‑catenin. DDX17 upregulation inhibited protein expression of SFRP4. Rescue assay confirmed that the addition of SFRP4 partially reversed ghrelin‑enhanced protein levels of cardiac‑specific markers and the fluorescence intensity of α‑MHC. In conclusion, ghrelin promoted cardiomyocyte differentiation of ADMSCs by DDX17‑mediated regulation of the SFRP4/Wnt/β‑catenin axis.
研究领域:
干细胞生物学
·
心血管研究
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分子生物学
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Drug Design Development and Therapy
·
2020
·
IF 3.216
Xuan Zou,Yang Wang,Yuheng Wang,Junting Yang,Huishu Guo,Zhengxu Cai
Introduction Paeoniflorin is a main active component in traditional Chinese medicine. Paeoniae alba radix is widely used as a spasmolytic and pain-relieving agent for abdominal spasmodic pain. Functional dyspepsia (FD) is characterized by pain or burning in the epigastrium, fullness, bloating and nausea. However, limited information is available about the effect of paeoniflorin on FD. Materials and Methods In this study, iodoacetamide or clonidine-induced FD rat models were established to investigate the impacts of paeoniflorin on FD induced by different pathophysiologic disturbances. Results We found the therapeutic effect of paeoniflorin through assessing the gastric emptying, gastric accommodation and visceral hypersensitivity. This function of paeoniflorin was related to the release of acetylcholine (ACh), which was accompanied by reduced acetylcholinesterase (AchE) activity in stomach and hypothalamus. Paeoniflorin administration inhibited the cyclo-oxygenase-2 (COX-2) expression and increased the level of ghrelin in the stomach. Besides, the levels of occludin and ZO-1 were elevated in the duodenum from paeoniflorin-treated rats, suggesting the impaired duodenal barrier was ameliorated. Discussion These results indicate that paeoniflorin possesses the ability to alleviate functional dyspepsia.
研究领域:
药理学
·
胃肠病学
·
传统中药
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产品关联
DOI
PubMed
高影响因子
Food & Function
·
2023
·Vol. 14
·期 14
·6513-6525
·
IF 6.1
Tianxu Liu,Mengting Zhang,Ismail Muhammad Asif,Yonglin Wu,Bin Li,Ling Wang
Gastrointestinal dysmotility is a common cause of functional dyspepsia. As two kinds of polysaccharides derived from brown algae, fucoidan and laminarin possess many physiological properties; however, their relative abilities in regulating gastrointestinal motility have not been illustrated yet. In this study, we aimed to investigate the regulatory effect of fucoidan and laminarin on functional dyspepsia mice induced by loperamide. Mice with gastrointestinal dysmotility were treated with fucoidan (100 and 200 mg per kg bw) and laminarin (50 and 100 mg per kg bw). As a result, fucoidan and laminarin reversed the dysfunction mainly through regulating gastrointestinal hormones (motilin and ghrelin), the cholinergic pathway, the total bile acid level, c-kit protein expression, and gastric smooth muscle contraction-related gene expression (ANO1 and RYR3). Moreover, fucoidan and laminarin intervention modulated the gut microbiota profile including the altered richness of Muribaculaceae, Lachnospiraceae, and Streptococcus. The results indicated that fucoidan and laminarin may restore the rhythm of the migrating motor complex and regulate gut microecology. In conclusion, we provided evidence to support that fucoidan and laminarin might have potential abilities to regulate gastrointestinal motility.
研究领域:
药理学
·
胃肠病学
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微生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Bingqian Yang,Kaikai Li,Meng Niu,Jianying Wei,Siming Zhao,Caihua Jia,Yan Xu
Wheat bran is an abundant yet underutilized agricultural byproduct. Herein, the insoluble dietary fiber from wheat bran (WBIDF) was ultra-milled to investigate its impact on physicochemical properties and gastrointestinal emptying. SEM and CLSM showed that the laminar structure of WBIDF was disrupted as the particle size was significantly reduced. In the similar characteristic peaks appearing at 3410, 2925, 1635, 1041, and 895 cm −1 in the FT-IR spectra and at 2940, 1593, 1080, and 526 cm −1 in the Raman spectra, the peak intensity was increased as the particle size decreased. It may be that the hydrogen bonding between cellulose, hemicellulose, or other macromolecules was enhanced. X-ray diffraction showed cellulose type I results for all five samples. Correspondingly, the water-holding, swelling, and oil-holding capacities increased by 75.33 %, 52.62 %, and 75.00 %, respectively, in WBIDF-CW 1.8 compared with WBIDF-CWy. Additionally, smaller particle sizes had lower viscosity, thereby enhancing intestinal propulsion and gastric emptying rates. Enhanced contact of the cecal tissue growth factor with the intestinal mucosa delayed ghrelin secretion and stimulated the secretion of motilin, gastrin, and cholecystokinin. In conclusion, the particle sizes of WBIDF were reduced through ultramicro-grinding, leading to altered structure, enhanced hydration and oil-holding capacities, decreased viscosity, and improved gastrointestinal emptying capacity.
研究领域:
食品科学
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营养学
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胃肠病学
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显微镜学
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光谱学
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动物生理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF THROMBOSIS AND THROMBOLYSIS
·
2024
·
IF 2.3
He Chengjian,Song Xiaojing,Zhu Zigui,Xiao Yan,Chen Jiacheng,Yao Hongyi,Xie Rongjun
Ghrelin exerts widespread effects in several diseases, but its role and mechanism in Acute Traumatic Coagulopathy (ATC) are largely unknown. The effect of ghrelin on cell proliferation was examined using three assays: 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), Lactate Dehydrogenase (LDH), and flow cytometry. The barrier function of the endothelial cells was evaluated using the Trans-Endothelial Electrical Resistance (TEER) and the endothelial permeability assay. An ATC mouse model was established to evaluate the in vivo effects of ghrelin. The Ras homolog family member A (RhoA) overexpression plasmid or adenovirus was used to examine the molecular mechanism of ghrelin. Ghrelin enhanced Human Umbilical Vein Endothelial Cells (HUVEC) proliferation and endothelial cell barrier function and inhibited HUVEC permeability damage in vitro. Additionally, ghrelin decreased the activated Partial Thromboplastin Time (aPTT) and Prothrombin Time (PT) in mice blood samples in the ATC mouse model. Ghrelin also improved the pathological alterations in postcava. Mechanistically, ghrelin acts through the RhoA/ Rho-associated Coiled-coil Containing Kinases (ROCK)/ Myosin Light Chain 2 (MLC2) pathway. Furthermore, the protective effects of ghrelin, both in vitro and in vivo, were reversed by RhoA overexpression. Our findings demonstrate that ghrelin may reduce vascular endothelial cell damage and endothelial barrier dysfunction by blocking the RhoA pathway, suggesting that ghrelin may serve as a potential therapeutic target for ATC treatment. Graphical Abstract We explored the effects of ghrelin on coagulopathy and vascular endothelial injury in vivo by establishing an ATC mouse model, and investigated the effects of ghrelin on LPS-induced HUVECs cell damage in vitro. The RhoA overexpression plasmid or adenovirus was used to examine the molecular mechanism. Abbreviations : ATC =acute traumatic coagulopathy; HUVECs =Human Umbilical Vein Endothelial Cells; LPS =lipopolysaccharide; RhoA =The Ras homolog family member A; aPTT =activated partial thromboplastin time; PT =prothrombin time; TEER =trans-endothelial electrical resistance
研究领域:
血液学
·
血管生物学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）