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https://www.readbyqxmd.com/read/29345253/3-acetyl-oleanolic-acid-ameliorates-non-alcoholic-fatty-liver-disease-in-high-fat-diet-treated-rats-by-activating-ampk-related-pathways
#1
Qiong Ou-Yang, Chun-Xiao Xuan, Xue Wang, Han-Qiong Luo, Jin-E Liu, Lan-Lan Wang, Ting-Ting Li, Yu-Peng Chen, Jun Liu
3-Acetyl-oleanolic acid (3Ac-OA) is a derivative of oleanolic acid (OA), which has shown therapeutic beneficial effects on diabetes and metabolic syndrome. In this study we investigated whether 3Ac-OA exerted beneficial effect on non-alcoholic fatty liver disease (NAFLD) in rats and its potential underlying mechanisms. Treatment with 3Ac-OA (1-100 μmol/L) dose-dependently decreased the intracellular levels of total cholesterol (TC) and triglyceride (TG) in FFA-treated primary rat hepatocytes and human HepG2 cell lines in vitro...
January 18, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29331507/adropin-an-endocrine-link-between-the-biological-clock-and-cholesterol-homeostasis
#2
Sarbani Ghoshal, Joseph R Stevens, Cyrielle Billon, Clemence Girardet, Sadichha Sitaula, Arthur S Leon, D C Rao, James S Skinner, Tuomo Rankinen, Claude Bouchard, Marinelle V Nuñez, Kimber L Stanhope, Deborah A Howatt, Alan Daugherty, Jinsong Zhang, Matthew Schuelke, Edward P Weiss, Alisha R Coffey, Brian J Bennett, Praveen Sethupathy, Thomas P Burris, Peter J Havel, Andrew A Butler
OBJECTIVE: Identify determinants of plasma adropin concentrations, a secreted peptide translated from the Energy Homeostasis Associated (ENHO) gene linked to metabolic control and vascular function. METHODS: Associations between plasma adropin concentrations, demographics (sex, age, BMI) and circulating biomarkers of lipid and glucose metabolism were assessed in plasma obtained after an overnight fast in humans. The regulation of adropin expression was then assessed in silico, in cultured human cells, and in animal models...
December 30, 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29322544/role-of-bisphenol-a-as-environmental-factor-in-the-promotion-of-non-alcoholic-fatty-liver-disease-in%C3%A2-vitro-and-clinical-study
#3
M Dallio, M Masarone, S Errico, A G Gravina, C Nicolucci, R Di Sarno, L Gionti, C Tuccillo, M Persico, P Stiuso, N Diano, C Loguercio, A Federico
BACKGROUND: Bisphenol A is an endocrine disrupting chemical associated with type 2 diabetes mellitus (T2DM), cardiovascular disease and liver enzyme abnormalities. AIM: To evaluate bisphenol A plasma and urine levels in non-alcoholic fatty liver disease (NAFLD) patients compared to healthy subjects. Furthermore, we evaluated, in human HepG2 cells, the effects of exposure to different concentrations of bisphenol A on both oxidative stress induction and cell proliferation...
January 11, 2018: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29319513/production-characterization-and-valuable-applications-of-exopolysaccharides-from-marine-bacillus-subtilis-sh1
#4
Sahar W M Hassan, Hassan A H Ibrahim
Exopolysaccharides (EPSs) are high molecular weight polymers consisting of different sugar residues they are preferable for replacing synthetic polymers as they are degradable and nontoxic. Many microorganisms possess the ability to synthesize and excrete exopolysaccharides with novel chemical compositions, properties and structures to have potential applications in different fields. The present study attempt to optimize the production of EPS by marine Bacillus subtilis SH1 in addition to characterization and investigation of different valuable applications...
December 4, 2017: Polish Journal of Microbiology
https://www.readbyqxmd.com/read/29319168/hepatic-mir-125b-inhibits-insulin-signaling-pathway-by-targeting-pik3cd
#5
Xiliang Du, Xiaobing Li, Liang Chen, Min Zhan, Lin Lei, Wenwen Gao, Zhen Shi, Yuhao Dong, Zhe Wang, Xinwei Li, Guowen Liu
Insulin resistance is often characterized as the most critical factor contributing to the development of (T2D) type 2 diabetes. MicroRNAs (miRNAs) are endogenous non-coding short single-stranded RNAs that function as negative regulators in many physiological and pathological processes. The objective of this study was to evaluate the roles of miR-125b in the regulation of insulin sensitivity in hepatocytes. We found that hepatic miR-125b levels were significantly increased in the patients with type 2 diabetes, high fat diet (HFD) mice, ob/ob and db/db mice...
January 10, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29295591/leonurus-japonicus-houtt-attenuates-nonalcoholic-fatty-liver-disease-in-free-fatty-acid-induced-hepg2-cells-and-mice-fed-a-high-fat-diet
#6
Mi-Ra Lee, Kwang Il Park, Jin Yeul Ma
We investigated the effects of a Leonurus japonicus ethanol extract (LJE) on nonalcoholic fatty liver disease (NAFLD). An in vitro model of hepatic steatosis was treated with 1 mM free fatty acid (FFA) in HepG2 cells. An in vivo NAFLD model was established using C57BL/6 mice fed a high-fat diet (HFD) and administered LJE (100 or 200 mg/kg) orally for 14 weeks. LJE treatment suppressed lipid accumulation and intracellular triglyceride levels significantly in a concentration-dependent manner in HepG2 cells. Moreover, LJE significantly reduced the expression of sterol regulatory element binding protein 1-c, and its downstream genes, which are associated with lipogenesis, in HepG2 cells...
December 25, 2017: Nutrients
https://www.readbyqxmd.com/read/29258820/p53-modulates-hepatic-insulin-sensitivity-through-nf-%C3%AE%C2%BAb-and-p38-erk-mapk-pathways
#7
Shanshan Geng, Weiwei Zhu, Shijia Wang, Chunfeng Xie, Xiaoting Li, Jieshu Wu, Yuan Li, Yue Chen, Xiaoqian Wang, Yu Meng, Qi Zhang, Jiaqi Chen, Caiyun Zhong
Besides its well-established oncosuppressor activity, the role of p53 in regulating metabolic pathways has been recently identified. Nevertheless, the function of p53 with respect to insulin resistance appears highly controversial. To address this issue, we investigated the expression of p53 in experimental model of insulin resistance. Then we used activator (nutlin-3α) and inhibitor (pifithrin-α, PFT-α) of p53 in HepG2 cell. Here we showed that p53 protein level was decreased in the hepatic tissue of high-fat diet-induced insulin resistance mice, genetically diabetic ob/ob mice and palmitate (PA) treated HepG2 cells...
December 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29220052/hypoglycemic-and-hypolipidemic-effects-of-anthocyanins-extract-from-black-soybean-seed-coat-in-high-fat-diet-and-streptozotocin-induced-diabetic-mice
#8
Zhongqin Chen, Cong Wang, Yuxiang Pan, Xudong Gao, Haixia Chen
Black soybean seed coat extract (BSSCE) is a rich source of anthocyanins with multiple health effects. This study was aimed at investigating the composition and hypoglycemic and hypolipidemic effects of BSSCE in vitro and in a high-fat diet and streptozotocin (STZ)-induced diabetic mice. The anthocyanins of BSSCE were identified as cyanidin-3-O-glucoside, delphinidin-3-O-glucoside, and peonidin-3-O-glucoside by HPLC-MS. Results demonstrated that BSSCE exhibited strong inhibitory activities for α-amylase, potent inhibition activity against lipid accumulation in HepG2 cells and protection effect on H2O2-induced oxidative stress-damaged HepG2 cells...
December 8, 2017: Food & Function
https://www.readbyqxmd.com/read/29207650/upregulation-of-mir-181a-impairs-hepatic-glucose-and-lipid-homeostasis
#9
Xiliang Du, Yuchen Yang, Chuang Xu, Zhicheng Peng, Min Zhang, Lin Lei, Wenwen Gao, Yuhao Dong, Zhen Shi, Xudong Sun, Zhe Wang, Xiaobing Li, Xinwei Li, Guowen Liu
The contributions of altered post-transcriptional gene silencing to the development of metabolic disorders remain poorly understood thus far. The objective of this study was to evaluate the roles of miR-181a in the regulation of hepatic glucose and lipid metabolism. MiR-181a is abundantly expressed in the liver, and we found that blood and hepatic miR-181a levels were significantly increased in patients and dairy cows with non-alcoholic fatty liver disease, as well as in high-fat diet and ob/ob mice. We determined that sirtuin1 is a target of miR-181a...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29207101/diosgenin-prevents-high-fat-diet-induced-rat-non-alcoholic-fatty-liver-disease-through-the-ampk-and-lxr-signaling-pathways
#10
Silu Cheng, Shufang Liang, Qun Liu, Zhengting Deng, Yuanhui Zhang, Juan Du, Ya'ni Zhang, Shu Li, Binbin Cheng, Changquan Ling
Non-alcoholic fatty liver disease (NAFLD) is a major public health concern worldwide. The aim of the present study was to observe the effect of diosgenin on NAFLD and investigate the underlying mechanisms. Diosgenin treatment increased the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in HepG2 cells. Diosgenin significantly inhibited high glucose (HG)-induced triglyceride (TG) accumulation and sterol regulatory element‑binding protein-1c (SREBP-1c) mRNA increase in HepG2 cells, which were partially abolished by the AMPK inhibitor compound C...
November 28, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29184391/novel-production-method-of-innovative-antiangiogenic-and-antitumor-small-peptides-in-escherichia-coli
#11
Sarra Setrerrahmane, Jian Yu, Jingchao Hao, Heng Zheng, Hanmei Xu
Background: Developing innovative drugs with potent efficacy, specificity, and high safety remains an ongoing task in antitumor therapy development. In the last few years, peptide drugs have become attractive agents in cancer therapy. HM-3, mainly with antiangiogenic effect, and AP25, with an additional antiproliferative effect, are two peptides designed in our laboratory targeting αvβ3 and α5β1 integrins, respectively. The low molecular weight of the two peptides renders their recombinant expression very difficult, and the complicated structure of AP25 makes its chemical synthesis restricted, which presents a big challenge for its development...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29167318/trail-reduces-impaired-glucose-tolerance-and-nafld-in-the-high-fat-diet-fed-mouse
#12
Stella Bernardi, Barbara Toffoli, Veronica Tisato, Fleur Bossi, Stefania Biffi, Andrea Lorenzon, Giorgio Zauli, Paola Secchiero, Bruno Fabris
AIMS/HYPOTHESIS: Recent studies suggest that a circulating protein called TRAIL (TNF-related apoptosis-inducing ligand) may have an important role in the treatment of type 2 diabetes. It has been shown that TRAIL deficiency worsens diabetes and that TRAIL delivery, when it is given before disease onset, slows down its development. This study aimed at evaluating whether TRAIL had the potential to treat type 2 diabetes. METHODS: Thirty male C57BL/6J mice were randomized to a standard or a high-fat diet (HFD)...
November 22, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29163785/tm5441-a-plasminogen-activator-inhibitor-1-inhibitor-protects-against-high-fat-diet-induced-non-alcoholic-fatty-liver-disease
#13
Seon Myeong Lee, Debra Dorotea, Inji Jung, Tetsuo Nakabayashi, Toshio Miyata, Hunjoo Ha
Recent evidences showed that elevation of plasminogen activator inhibitor 1 (PAI-1) was responsible in mediating obesity-induced non-alcoholic fatty liver disease (NAFLD) and metabolic disorders. Here, we investigated the effect of TM5441, an oral PAI-1 inhibitor that lacks of bleeding risk, on high-fat diet (HFD)-induced NAFLD. HFD-fed C57BL/6J mice was daily treated with 20 mg/kg TM5441. To examine the preventive effect, 10-week-treatment was started along with initiation of HFD; alternatively, 4-week-treatment was started in mice with glucose intolerance in the interventional strategy...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29144590/metabolic-profiling-of-normal-hepatocyte-and-hepatocellular-carcinoma-cells-via-1-h-nuclear-magnetic-resonance-spectroscopy
#14
Yang Chen, Zhong Chen, Jiang-Hua Feng, Yun-Bin Chen, Nai-Shun Liao, Ying Su, Chang-Yan Zou
Hepatocellular carcinoma (HCC) causes death mainly by disseminated metastasis progression from the organ being confined. Different metastatic stages are closely related to cellular metabolic profiles. Normal hepatocyte and HepG2 cell line from low metastatic HCC were studied by NMR-based metabolomic techniques. Multivariate and univariate statistical analyses were utilized to identify characteristic metabolites from cells and cultured media. Elevated levels of acetate, creatine, isoleucine, leucine, and phenylalanine were observed in HepG2 cells, suggesting more active in gathering nutrient components along with altered amino acid metabolisms and enhanced lipid metabolism...
November 16, 2017: Cell Biology International
https://www.readbyqxmd.com/read/29109794/ginsenoside-rg1-inhibits-glucagon-induced-hepatic-gluconeogenesis-through-akt-foxo1-interaction
#15
Qun Liu, Fei-Ge Zhang, Wen-Song Zhang, An Pan, Yi-Lin Yang, Jin-Feng Liu, Ping Li, Bao-Lin Liu, Lian-Wen Qi
Rationale: Glucagon is involved in hepatic gluconeogenesis, playing a key role in type 2 diabetes. Ginsenosides are reported to have antidiabetic activities. Ginsenoside Rg1 is a major propanaxatriol-type saponin in ginseng. This study aims to investigate the regulatory effects of Rg1 on glucagon-induced hepatic glucose production. Methods: The effects of Rg1 were investigated in high-fat-diet (HFD)-fed mice and glucagon-challenged C57BL/6J mice. Glucose metabolism was evaluated by oral glucose tolerance test and pyruvate tolerance test...
2017: Theranostics
https://www.readbyqxmd.com/read/29064442/enhanced-glucose-uptake-in-human-liver-cells-and-inhibition-of-carbohydrate-hydrolyzing-enzymes-by-nordic-berry-extracts
#16
Giang Thanh Thi Ho, Thi Kim Yen Nguyen, Eili Tranheim Kase, Margey Tadesse, Hilde Barsett, Helle Wangensteen
A Western lifestyle with low physical activity and a diet rich in sugar, fat and processed food contribute to higher incidences of diabetes and obesity. Enhanced glucose uptake in human liver cells was observed after treatment with phenolic extracts from different Nordic berries. All berry extracts showed higher inhibition against α-amylase and α-glucosidase than the anti-diabetic agent acarbose. Total phenolic content and phenolic profiles in addition to antioxidant activities, were also investigated. The berries were extracted with 80% methanol on an accelerated solvent extraction system (ASE) and then purified by C-18 solid phase extraction (SPE)...
October 24, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29052178/hmga1-is-a-novel-transcriptional-regulator-of-the-foxo1-gene
#17
Biagio Arcidiacono, Eusebio Chiefari, Sebastiano Messineo, Francesco L Bilotta, Ida Pastore, Domenica M Corigliano, Daniela P Foti, Antonio Brunetti
PURPOSE: The forkhead transcription factor (FoxO1) is a master transcriptional regulator of fundamental cellular processes ranging from cell proliferation and differentiation to inflammation and metabolism. However, despite its relevance, the mechanism(s) underlying FoxO1 gene regulation are largely unknown. We have previously shown that the chromatin factor high-mobility group A1 (HMGA1) plays a key role in the transcriptional regulation of glucose-responsive genes, including some that are involved in FoxO1-mediated glucose metabolism...
October 19, 2017: Endocrine
https://www.readbyqxmd.com/read/29042441/transcription-factor-19-interacts-with-histone-3-lysine-4-trimethylation-and-controls-gluconeogenesis-via-the-nucleosome-remodeling-deacetylase-complex
#18
Sabyasachi Sen, Sulagna Sanyal, Dushyant Kumar Srivastava, Dipak Dasgupta, Siddhartha Roy, Chandrima Das
Transcription Factor 19 (TCF19) has been reported as type 1 diabetes associated locus involved in maintenance of pancreatic β cells through a fine-tuned regulation of cell proliferation and apoptosis. TCF19 also exhibits genomic association with type 2 diabetes, although the precise molecular mechanism remains unknown. It harbours both a plant homeodomain (PHD) and a forkhead-associated domain (FHA) implicated in epigenetic recognition and gene regulation, a phenomenon that has remained unexplored. Here, we show that TCF19 selectively interacts with histone 3 lysine 4 trimethylation (H3K4Me3) through its PHD finger...
October 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29021286/pomegranate-juice-but-not-an-extract-confers-a-lower-glycemic-response-on-a-high-glycemic-index-food-randomized-crossover-controlled-trials-in-healthy-subjects
#19
Asimina Kerimi, Hilda Nyambe-Silavwe, Julia S Gauer, Francisco A Tomás-Barberán, Gary Williamson
Background: Low-glycemic index diets have demonstrated health benefits associated with a reduced risk of developing type 2 diabetes.Objectives: We tested whether pomegranate polyphenols could lower the glycemic response of a high-glycemic index food when consumed together and the mechanism by which this might occur.Design: We compared the acute effect of a pomegranate juice and a polyphenol-rich extract from pomegranate (supplement) on the bread-derived postprandial blood glucose concentration in 2 randomized, crossover, controlled studies (double-blinded for the supplements), each on 16 healthy volunteers...
October 11, 2017: American Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28988629/design-and-synthesis-of-a-novel-series-of-orally-active-selective-somatostatin-receptor-2-agonists-for-the-treatment-of-type-2-diabetes
#20
Yoshihiro Banno, Shigekazu Sasaki, Makoto Kamata, Jun Kunitomo, Yasufumi Miyamoto, Hidenori Abe, Naohiro Taya, Satoru Oi, Masanori Watanabe, Tomoko Urushibara, Masatoshi Hazama, Shin-Ichi Niwa, Saku Miyamoto, Akira Horinouchi, Ken-Ichi Kuroshima, Nobuyuki Amano, Shin-Ichi Matsumoto, Shinichiro Matsunaga
The discovery of a novel series of β-methyltryptophan (β MeTrp) derivatives as selective and orally active non-peptide somatostatin receptor 2 (SSTR2) agonists for the treatment of Type 2 diabetes is described. In our previous research, Compound A, β-MeTrp derivative with highly potent and selective SSTR2 agonistic activity IC50 (SSTR2/SSTR5)=0.3/>100 (nM), was identified asa drug candidate for treatment of Type 2 diabetes which lowers significantly plasma glucose level in Wistar fatty rats in its oral administrations...
November 1, 2017: Bioorganic & Medicinal Chemistry
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