scholarly journals Finger Citron Extract Ameliorates Glycolipid Metabolism and Inflammation by Regulating GLP-1 Secretion via TGR5 Receptors in Obese Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Yujiao Yang ◽  
Aofei Tian ◽  
Zhen Wu ◽  
Yao Wei ◽  
Xuguang Hu ◽  
...  
Keyword(s):  
Endocrine Cells ◽  
Liver Lipid ◽  
Chinese Herbs ◽  
Rat Colon ◽  
Enzyme Linked Immunosorbent Assay ◽  
Colon Tissue ◽  
Glycolipid Metabolism ◽  
Obese Rats ◽  
Intestinal Endocrine Cells

Finger citron (FC) is one of many traditional Chinese herbs that have been used to treat obesity. The aim of this study was to elucidate the pharmacological effects and mechanisms of FC on obese rats. Rats were fed with a high-fat diet as a model of obesity and treated with FC at three different dosages for 6 weeks. Pathology in liver tissue was observed. Glucose levels, lipids levels, and inflammatory indicators in serum were evaluated by enzyme‐linked immunosorbent assay. Furthermore, the expression of G protein-coupled receptor 5 (TGR5) pathway genes in rat colon tissue was detected by reverse transcription-polymerase chain reaction analysis (RT-PCR). Our result revealed that FC alleviates obesity by reducing body weight (BW) and waist circumference, managing inflammation and improving glycolipid metabolism, liver function, and liver lipid peroxidation in vivo. In addition, the mechanism of FC on obesity is possibly the stimulation of glucagon-like peptide-1 (GLP-1) secretion by activating the TGR5 pathway in intestinal endocrine cells. Our studies highlight the obesity reduction effects of FC and one of the mechanisms may be the activation of the TGR5 pathway in intestinal endocrine cells.

scholarly journals Endocrine taste cells

2014 ◽  
Vol 111 (S1) ◽  
pp. S23-S29 ◽  
Author(s):  
Zaza Kokrashvili ◽  
Karen K. Yee ◽  
Erwin Ilegems ◽  
Ken Iwatsuki ◽  
Yan Li ◽  
...  
Keyword(s):  
Endocrine Cells ◽  
Gut Hormones ◽  
Taste Receptors ◽  
Wild Type ◽  
Oral Stimulation ◽  
Cephalic Phase ◽  
Taste Cells ◽  
Glucagon Like Peptide 1 ◽  
Intestinal Endocrine Cells

In taste cells, taste receptors, their coupled G proteins and downstream signalling elements mediate the detection and transduction of sweet, bitter and umami compounds. In some intestinal endocrine cells, taste receptors and gustducin contribute to the release of glucagon-like peptide 1 (GLP-1) and other gut hormones in response to glucose and non-energetic sweeteners. Conversely, taste cells have been found to express multiple hormones typically found in intestinal endocrine cells, e.g. GLP-1, glucagon, somatostatin and ghrelin. In the present study, by immunohistochemistry, multiple subsets of taste cells were found to express GLP-1. The release of GLP-1 from ‘endocrine taste cells’ into the bloodstream was examined. In wild-type mice, even after oesophagectomy and vagotomy, oral stimulation with glucose induced an elevation of GLP-1 levels in the bloodstream within 10 min. Stimulation of taste cell explants from wild-type mice with glucose led to the release of GLP-1 into the medium. Knocking out of the Tas1r3 gene did not eliminate glucose-stimulated GLP-1 release from taste cells in vivo. The present results indicate that a portion of the cephalic-phase rise in circulating GLP-1 levels is mediated by the direct release of GLP-1 from taste cells into the bloodstream.

scholarly journals HNF1α Controls Liver Lipid Metabolism and Insulin Resistance via Negatively Regulating the SOCS-3-STAT3 Signaling Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Jiaorong Tan ◽  
Jiahong Xu ◽  
Guohua Wei ◽  
Lijuan Zhang ◽  
Long’e Sun ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Liver Lipid ◽  
Fatty Degeneration ◽  
Glycolipid Metabolism ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway

This study is aimed at evaluating the effects, functions, and mechanism of HNF1α on hepatic glycolipid metabolism. In this study, free fatty acid- (FFA-) induced steatosis of hepatocyte liver cell LO2 was used as an in vitro model. The methods of Oil Red O staining, RT-qPCR, western blot, and immunofluorescence staining were used to detect LO2-regulated HNF1α expression and its effects on FFA-induced LO2 cell steatosis, the insulin signaling and SOCS-3-STAT3 signaling pathways, the expression of lipid metabolism-related regulators, and phosphorylation. With increased FFA induction time, the expression of HNF1α in the LO2 fatty degeneration hepatic cells gradually decreased. Downregulation of HNF1α expression aggravated FFA-induced steatosis of LO2 hepatocytes. HNF1α promotes activation of the insulin pathway and oxidative breakdown of fat and inhibits lipid anabolism. Inhibitors of STAT3 can reverse the regulation of decreased HNF1α expression on the insulin signaling pathway and fat metabolism. We also confirmed this pathway using HNF1α-/- mice combining treatment with STAT3 inhibitor NSC 74859 in vivo. HNF1α regulates hepatic lipid metabolism by promoting the expression of SOCS-3 and negatively regulating the STAT3 signaling pathway.

scholarly journals The Novel Hepatokine Ectodysplasin A Is Increased in Obesity and Reduced after Liraglutide Management

2021 ◽  
Author(s):  
Zhensheng Cai ◽  
Xia Deng ◽  
Panpan Zhang ◽  
Zhicong Zhao ◽  
Chang Guo ◽  
...  
Keyword(s):  
Weight Loss ◽  
Metabolic Diseases ◽  
Liver Lipid ◽  
Physiological Role ◽  
Normal Weight ◽  
Enzyme Linked Immunosorbent Assay ◽  
Liver Lipid Metabolism ◽  
Mrna And Protein Expression

Abstract Background Ectodysplasin A (EDA), a new hepatokine, has been recently characterized to play a role in liver lipid metabolism and insulin resistance, but its physiological role remains scarcely acquainted in obesity. This study was the first time to determine the level of serum EDA in obesity, and to assess change in the levels of EDA after weight loss in obese mice.Methods We analyzed the serum concentrations of EDA by enzyme-linked immunosorbent assay (ELISA) in 60 subjects including 30 normal weight and 30 obesity. Male C57BL/6J mice were fed with high-fat diet and injected by liraglutide to reduce weight. AML12 cells were induced by palmitic acid and treated with liraglutide. Quantitative real-time PCR and Western blot analysis were conducted to evaluate the expression of EDA. Results Serum EDA levels were significantly higher in obesity than in normal weight subjects. It was positively correlated with body mass index (BMI). More importantly, the mRNA and protein expression of EDA reduced after liraglutide management in vivo and in vitro.Conclusions The level of EDA increased significantly in obesity and decreased significantly after weight loss. It is suggested that EDA may be a novel hepatokine associated with obesity-related metabolic diseases.

scholarly journals RYGB increases postprandial gastric nesfatin-1 and rapid relieves NAFLD via gastric nerve detachment

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0243640
Author(s):  
Geng Wang ◽  
Qingbo Wang ◽  
Jie Bai ◽  
Gang Li ◽  
Kaixiong Tao ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Portal Vein ◽  
Liver Lipid ◽  
Negative Control ◽  
Enzyme Linked Immunosorbent Assay ◽  
Induction Effect ◽  
Nonalcoholic Fatty Liver ◽  
Post Surgery

Background Roux-en-Y gastric bypass (RYGB) could reduce nonalcoholic fatty liver disease (NAFLD) ahead of the weight-loss effects. But the detailed mechanisms remain unclear. Material and methods A high-fat diet (HFD) was fed to induce obesity. RYGB was then performed. Gastric nesfatin-1 was measured by enzyme-linked immunosorbent assay (ELISA) in portal vein and polymerase chain reaction (PCR) in gastric tissues. Modified surgeries including vagus-preserved bypass and vagectomy were performed and postprandial gastric nesfatin-1 were analyzed. The effects of nesfatin-1 on hepatocytes were studied by PCR and immunohistochemistry. Both intraperitoneal and intracerebroventricular injection (ICV) were performed to analyze the in vivo effects on liver lipid metabolism. Results Increased postprandial portal vein nesfatin-1 was observed in RYGB but not in control groups. This increase is mainly due to induction of gastric nesfatin-1. A modified RYGB in which the gastric vagus is preserved is conducted and, in this case, this nesfatin-1 induction effect is diminished. Mere vagectomy could also induce a similar nesfatin-1 increase pattern. The infusion of nesfatin-1 in the brain could inhibit the expression of gastric nesfatin-1, and the effects are diminished after gastric vagectomy. In vivo and in vitro nesfatin-1 stimulation in the liver resulted in improvements in lipid metabolism. Conclusions Severing the gastric vagus during RYGB could cut off the negative control from the central nervous system (CNS) and result in increased postprandial gastric nesfatin-1 post surgery, which in turn, improves NAFLD.

scholarly journals Lingonberry Fruit Ethanol Extract Ameliorates DSS-Induced Ulcerative Colitis In Vivo and In Vitro

2021 ◽  
Vol 11 (17) ◽  
pp. 7955
Author(s):  
Yong-Deok Jeon ◽  
Ji-Hyun Lee ◽  
Sa-Haeng Kang ◽  
Hyun Myung ◽  
Jong-Sik Jin
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Cytokines ◽  
Ethanol Extract ◽  
Treated Group ◽  
Mouse Serum ◽  
Enzyme Linked Immunosorbent Assay ◽  
Colon Tissue ◽  
Pg E2

Ulcerative colitis (UC) is an inflammatory chronic intestinal disease with pathological characteristics, including imbalanced immune function and the overexpression of inflammatory cytokines and mediators. Inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-1, and IL-6) were oversecreted in UC condition. Cyclooxygenase (COX)-2 and prostaglandin (PG)E2 were also overexpressed in colon tissue. Lingonberry (LB) (Vaccinium vitis-idaea L.) possesses pharmacological activities, including anti-oxidant, anti-cancer, and anti-obesity effects. To explore LB’s effects on UC, BALB/c mice were administered with 3% (w/v) dextran sulphate sodium (DSS) and LB extract (70% ethanol) orally for nine days. The severity of UC was measured by the change in body weight and colon length. To evaluate LB’s regulatory effect on inflammatory cytokines, the enzyme-linked immunosorbent assay (ELISA) kit was used to measure the inflammatory cytokines in mouse serum. Mouse peritoneal microphages were used to detect LB’s anti-inflammatory effect. The results showed that LB treatment ameliorated less weight loss and longer colon length compared to the DSS-treated group. LB treatment also ameliorated the secretion of inflammatory cytokines. These results indicated that LB has potential as an herbal medicine to treat UC.

scholarly journals The impact of FGF19/FGFR4 signaling inhibition in antitumor activity of multi-kinase inhibitors in hepatocellular carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hiroaki Kanzaki ◽  
Tetsuhiro Chiba ◽  
Junjie Ao ◽  
Keisuke Koroki ◽  
Kengo Kanayama ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Mechanisms ◽  
Kinase Inhibitors ◽  
Progression Free Survival ◽  
Erk Signaling ◽  
Enzyme Linked Immunosorbent Assay ◽  
Antitumor Effects ◽  
The Impact

AbstractFGF19/FGFR4 autocrine signaling is one of the main targets for multi-kinase inhibitors (MKIs). However, the molecular mechanisms underlying FGF19/FGFR4 signaling in the antitumor effects to MKIs in hepatocellular carcinoma (HCC) remain unclear. In this study, the impact of FGFR4/ERK signaling inhibition on HCC following MKI treatment was analyzed in vitro and in vivo assays. Serum FGF19 in HCC patients treated using MKIs, such as sorafenib (n = 173) and lenvatinib (n = 40), was measured by enzyme-linked immunosorbent assay. Lenvatinib strongly inhibited the phosphorylation of FRS2 and ERK, the downstream signaling molecules of FGFR4, compared with sorafenib and regorafenib. Additional use of a selective FGFR4 inhibitor with sorafenib further suppressed FGFR4/ERK signaling and synergistically inhibited HCC cell growth in culture and xenograft subcutaneous tumors. Although serum FGF19high (n = 68) patients treated using sorafenib exhibited a significantly shorter progression-free survival and overall survival than FGF19low (n = 105) patients, there were no significant differences between FGF19high (n = 21) and FGF19low (n = 19) patients treated using lenvatinib. In conclusion, robust inhibition of FGF19/FGFR4 is of importance for the exertion of antitumor effects of MKIs. Serum FGF19 levels may function as a predictive marker for drug response and survival in HCC patients treated using sorafenib.

scholarly journals Pirfenidone attenuates synovial fibrosis and postpones the progression of osteoarthritis by anti-fibrotic and anti-inflammatory properties in vivo and in vitro

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Qilu Wei ◽  
Ning Kong ◽  
Xiaohui Liu ◽  
Run Tian ◽  
Ming Jiao ◽  
...  
Keyword(s):  
Protein Expression ◽  
Cell Counting ◽  
Enzyme Linked Immunosorbent Assay ◽  
Fast Green ◽  
Expression Levels ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Safranin O ◽  
Tgf Β1

Abstract Background Osteoarthritis (OA) is a disease of the entire joint involving synovial fibrosis and inflammation. Pathological changes to the synovium can accelerate the progression of OA. Pirfenidone (PFD) is a potent anti-fibrotic drug with additional anti-inflammatory properties. However, the influence of PFD on OA is unknown. Methods Proliferation of human fibroblast-like synoviocytes (FLSs) after treatment with TGF-β1 or PFD was evaluated using a Cell Counting Kit-8 assay and their migration using a Transwell assay. The expression of fibrosis-related genes (COL1A1, TIMP-1, and ACTA-2) and those related to inflammation (IL-6 and TNF-α) was quantified by real-time quantitative PCR. The protein expression levels of COL1A1, α-SMA (coded by ACTA-2), IL-6 and TNF-α were measured by enzyme-linked immunosorbent assay. A rabbit model of OA was established and then PFD was administered by gavage. The expression of genes related to fibrosis (COL1A1, TIMP-1, and ADAM-12) and inflammation (IL-6 and TNF-α) was measured using RNA extracted from the synovium. Synovial tissue was examined histologically after staining with H&E, Masson’s trichrome, and immunofluorescence. Synovitis scores, the volume fraction of collagen, and mean fluorescence intensity were calculated. Degeneration of articular cartilage was analyzed using a Safranin O-fast green stain and OARSI grading. Results The proliferation of FLSs was greatest when induced with 2.5 ng/ml TGF-β1 although it did not promote their migration. Therefore, 2.5 ng/ml TGF-β1 was used to stimulate the FLSs and evaluate the effects of PFD, which inhibited the migration of FLSs at concentrations as low as 1.0 mg/ml. PFD decreased the expression of COL1A1 while TGF-β1 increased both mRNA and protein expression levels of IL-6 but had no effect on α-SMA or TNF-α expression. PFD decreased mRNA expression levels of COL1A1, IL-6, and TNF-α in vivo. H&E staining and synovitis scores indicated that PFD reduced synovial inflammation, while Masson’s trichrome and immunofluorescence staining suggested that PFD decreased synovial fibrosis. Safranin O-Fast Green staining and the OARSI scores demonstrated that PFD delayed the progression of OA. Conclusions PFD attenuated synovial fibrosis and inflammation, and postponed the progression of osteoarthritis in a modified Hulth model of OA in rabbits, which was related to its anti-fibrotic and anti-inflammatory properties.

scholarly journals A Novel Mouse Monoclonal Antibody C42 against C-Terminal Peptide of Alpha-1-Antitrypsin

2021 ◽  
Vol 22 (4) ◽  
pp. 2141
Author(s):  
Srinu Tumpara ◽  
Elena Korenbaum ◽  
Mark Kühnel ◽  
Danny Jonigk ◽  
Beata Olejnicka ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Flow Cytometry ◽  
Western Blotting ◽  
Complex Mixture ◽  
Immunoglobulin M ◽  
Confocal Laser ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dot Blot

The C-terminal-fragments of alpha1-antitrypsin (AAT) have been identified and their diverse biological roles have been reported in vitro and in vivo. These findings prompted us to develop a monoclonal antibody that specifically recognizes C-36 peptide (corresponding to residues 359–394) resulting from the protease-associated cleavage of AAT. The C-36-targeting mouse monoclonal Immunoglobulin M (IgM) antibody (containing κ light chains, clone C42) was generated and enzyme-linked immunosorbent assay (ELISA)-tested by Davids Biotechnologie GmbH, Germany. Here, we addressed the effectiveness of the novel C42 antibody in different immunoassay formats, such as dot- and Western blotting, confocal laser microscopy, and flow cytometry. According to the dot-blot results, our novel C42 antibody detects the C-36 peptide at a range of 0.1–0.05 µg and shows no cross-reactivity with native, polymerized, or oxidized forms of full-length AAT, the AAT-elastase complex mixture, as well as with shorter C-terminal fragments of AAT. However, the C42 antibody does not detect denatured peptide in SDS-PAGE/Western blotting assays. On the other hand, our C42 antibody, unconjugated as well as conjugated to DyLight488 fluorophore, when applied for immunofluorescence microscopy and flow cytometry assays, specifically detected the C-36 peptide in human blood cells. Altogether, we demonstrate that our novel C42 antibody successfully recognizes the C-36 peptide of AAT in a number of immunoassays and has potential to become an important tool in AAT-related studies.

scholarly journals Baicalin Represses Type Three Secretion System of Pseudomonas aeruginosa through PQS System

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1497
Author(s):  
Pansong Zhang ◽  
Qiao Guo ◽  
Zhihua Wei ◽  
Qin Yang ◽  
Zisheng Guo ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Virulence Factors ◽  
Mammalian Cells ◽  
Secretion System ◽  
Chinese Herbs ◽  
Infection Model ◽  
Lung Pathology ◽  
Promising Alternative ◽  
The Impact

Therapeutics that target the virulence of pathogens rather than their viability offer a promising alternative for treating infectious diseases and circumventing antibiotic resistance. In this study, we searched for anti-virulence compounds against Pseudomonas aeruginosa from Chinese herbs and investigated baicalin from Scutellariae radix as such an active anti-virulence compound. The effect of baicalin on a range of important virulence factors in P. aeruginosa was assessed using luxCDABE-based reporters and by phenotypical assays. The molecular mechanism of the virulence inhibition by baicalin was investigated using genetic approaches. The impact of baicalin on P. aeruginosa pathogenicity was evaluated by both in vitro assays and in vivo animal models. The results show that baicalin diminished a plenty of important virulence factors in P. aeruginosa, including the Type III secretion system (T3SS). Baicalin treatment reduced the cellular toxicity of P. aeruginosa on the mammalian cells and attenuated in vivo pathogenicity in a Drosophila melanogaster infection model. In a rat pulmonary infection model, baicalin significantly reduced the severity of lung pathology and accelerated lung bacterial clearance. The PqsR of the Pseudomonas quinolone signal (PQS) system was found to be required for baicalin’s impact on T3SS. These findings indicate that baicalin is a promising therapeutic candidate for treating P. aeruginosa infections.

Expression of TAS2R14 in the intestinal endocrine cells of non-human primates

2021 ◽  
Author(s):  
Misa Hayashi ◽  
Akihiko Inaba ◽  
Miho Hakukawa ◽  
Ken Iwatsuki ◽  
Hiroo Imai ◽  
...  
Keyword(s):  
Endocrine Cells ◽  
Intestinal Endocrine Cells
Sign in / Sign up

Export Citation Format

Share Document