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https://www.readbyqxmd.com/read/28646531/morin-a-novel-lxr%C3%AE-%C3%AE-dual-antagonist-has-potent-therapeutic-efficacy-for-nonalcoholic-fatty-liver-diseases
#1
Ming Gu, Yu Zhang, Chuhe Liu, Dongshan Wang, Li Feng, Shengjie Fan, Baican Yang, Qingchun Tong, Guang Ji, Cheng Huang
BACKGROUND AND PURPOSE: Morin is a natural occurring flavonoid in many dietary plants and has a wide range of beneficial effects on metabolism; however, the mechanism underlying its action remains elusive. EXPERIMENTAL APPROACH: Reporter assay and the Time-Resolved Fluorescence Resonance Energy Transfer assay were used to identify morin as a dual antagonist of LXRα and LXRβ. High fat-diet mixed with morin (100 mg/100 g diet) was administrated to high-fat diet-induced obese or LXRβ(-/-) mice combining with Western blot and RT-PCR analysis to evaluate the pharmacological effect and mechanism of morin treatment...
June 23, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28587208/xyloketal-b-attenuates-fatty-acid-induced-lipid-accumulation-via-the-srebp-1c-pathway-in-nafld-models
#2
Youying Zhang, Tian Meng, Ling Zuo, Yu Bei, Qihao Zhang, Zhijian Su, Yadong Huang, Jiyan Pang, Qi Xiang, Hongtu Yang
The goal of this study was to examine the effects of xyloketal B on nonalcoholic fatty liver disease (NAFLD) and to explore the molecular mechanisms underlying its effects in both in vivo and in vitro models. We discovered an association between xyloketal B and the sterol regulatory element-binding protein-1c (SREBP-1c) signaling pathway, which is related to lipid metabolism. Mice were dosed with xyloketal B (5, 10 and 20 mg/kg/d) and atorvastatin (15 mg/kg/d) via intraperitoneal injection once daily for 40 days after being fed a high fat diet plus 10% high fructose liquid (HFD+HFL) for 8 weeks...
June 3, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28578672/sake-lees-extract-improves-hepatic-lipid-accumulation-in-high-fat-diet-fed-mice
#3
Hisako Kubo, Masato Hoshi, Takuya Matsumoto, Motoko Irie, Shin Oura, Hiroko Tsutsumi, Yoji Hata, Yasuko Yamamoto, Kuniaki Saito
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is increasing worldwide as one of the leading causes of chronic liver disease. Sake lees (SL) are secondary products of sake manufacturing and are considered to have beneficial effects on human health. To investigate these effects, we used high fat diet (HFD)-fed mice treated with or without the SL extract. METHOD: Mice were the HFD ad libitum for 8 weeks and were administered 500 μL of distilled water with or without the SL extract (350 mg/mL) by a feeding needle daily for the last 4 weeks...
June 3, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28566408/5-ala-ameliorates-hepatic-steatosis-through-ampk-signaling-pathway
#4
Haoyong Yu, Mingliang Zhang, Yunqin Ma, Junxi Lu, Pan Pan, Haibing Chen, Weiping Jia
5-Aminolevulinic acid (5-ALA), the first compound in the porphyrin synthesis pathway, has been reported to ameliorate the diabetic state in Otsuka Long-Evans Tokushima Fatty rats by reducing fat pad weight in the retroperitoneal region. Dietary supplementation with 5-ALA has additionally demonstrated the capacity to lower blood glucose and HbA1c levels among subjects with diabetes. The etiology of Nonalcoholic Fatty Liver Disease (NAFLD) is complex and its typical characteristics include obesity and insulin resistance...
May 31, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28534956/effects-of-octreotide-on-hepatic-glycogenesis-in-rats-with-high-fat-diet%C3%A2-induced-obesity
#5
Xiao-Xia Wang, Ting Ye, Mao Li, Xian Li, Ou Qiang, Cheng-Wei Tang, Rui Liu
Reduced hepatic glycogenesis is one of the most important causes of metabolic abnormalities in non‑alcoholic fatty liver disease. Octreotide, a somatostatin analogue, has been demonstrated to promote weight loss and improve metabolic disorders in mice with high fat diet (HFD)‑induced obesity. However, whether octreotide affects hepatic glycogenesis is unknown. The aim of the present study was to verify the effects of octreotide on hepatic glycogenesis in rats with HFD‑induced obesity. Male Sprague‑Dawley rats were fed a standard diet or a HFD for 24 weeks...
July 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28534819/ginsenoside-rb2-alleviates-hepatic-lipid-accumulation-by-restoring-autophagy-via-induction-of-sirt1-and-activation-of-ampk
#6
Qi Huang, Ting Wang, Liu Yang, He-Yao Wang
Although Panax ginseng is a famous traditional Chinese medicine and has been widely used to treat a variety of metabolic diseases including hyperglycemia, hyperlipidemia, and hepatosteatosis, the effective mediators and molecular mechanisms remain largely unknown. In this study we found that ginsenoside Rb2, one of the major ginsenosides in Panax ginseng, was able to prevent hepatic lipid accumulation through autophagy induction both in vivo and in vitro. Treatment of male db/db mice with Rb2 significantly improved glucose tolerance, decreased hepatic lipid accumulation, and restored hepatic autophagy...
May 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28496041/a-rapid-mitochondrial-toxicity-assay-utilizing-rapidly-changing-cell-energy-metabolism
#7
Yosuke Sanuki, Tetsuro Araki, Osamu Nakazono, Kazuyuki Tsurui
Drug-induced liver injury is a major cause of safety-related drug-marketing withdrawals. Several drugs have been reported to disrupt mitochondrial function, resulting in hepatotoxicity. The development of a simple and effective in vitro assay to identify the potential for mitochondrial toxicity is thus desired to minimize the risk of causing hepatotoxicity and subsequent drug withdrawal. An in vitro test method called the "glucose-galactose" assay is often used in drug development but requires prior-culture of cells over several passages for mitochondrial adaptation, thereby restricting use of the assay...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28474165/evaluation-of-99m-tc-3prgd2-integrin-receptor-imaging-in-hepatocellular-carcinoma-tumour-bearing-mice-comparison-with-18-f-fdg-metabolic-imaging
#8
Jieling Zheng, Weibing Miao, Chao Huang, Haoxue Lin
OBJECTIVE: Our study was designed to explore the utility of (99m)Tc-HYNIC-PEG4-E[PEG4-c(RGDfK)]2 ((99m)Tc-3PRGD2) for the detection of hepatocellular carcinoma (HCC) and specifically to compare the diagnostic performance of (99m)Tc-3PRGD2 integrin receptor imaging and 2-18-fluoro-2-deoxy-D-glucose ((18)F-FDG) metabolic imaging in a nude mouse model. METHODS: (99m)Tc-3PRGD2 was synthesized using a HYNIC-3PRGD2 lyophilized kit with (99m)TcO4 labelling. The nude mouse animal model was established by subcutaneously injecting 5 × 10(7)/ml HepG2 cells into the shoulder flank of each mouse...
May 4, 2017: Annals of Nuclear Medicine
https://www.readbyqxmd.com/read/28472477/fibronectin-type-iii-domain-containing-protein-5-rs3480-a-g-polymorphism-irisin-and-liver-fibrosis-in-patients-with-nonalcoholic-fatty-liver-disease
#9
Salvatore Petta, Luca Valenti, Gianluca Svegliati-Baroni, Massimiliano Ruscica, Rosaria Maria Pipitone, Paola Dongiovanni, Chiara Rychlicki, Nicola Ferri, Calogero Cammà, Anna Ludovica Fracanzani, Irene Pierantonelli, Vito Di Marco, Marica Meroni, Debora Giordano, Stefania Grimaudo, Marco Maggioni, Daniela Cabibi, Silvia Fargion, Antonio Craxì
Context: Contrasting data have been reported on the role of irisin, a novel myokine encoded by the FNDC5 gene, in NAFLD pathogenesis. We tested in patients with suspected NASH the association of FNDC5 variants, hepatic expression and circulating irisin with liver damage(F2-F4 fibrosis as main outcome). We also investigated whether irisin modulates hepatocellular fat accumulation and stellate cell activation in experimental models. Methods: We considered 593 consecutive patients, who underwent liver biopsy for suspected NASH and 192 patients with normal liver enzymes and without steatosis...
May 3, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28463418/use-of-primary-rat-hepatocytes-for-prediction-of-drug-induced-mitochondrial-dysfunction
#10
Cong Liu, Shuichi Sekine, Binbin Song, Kousei Ito
Mitochondrial dysfunction plays a central role in drug-induced liver injury. To evaluate drug-induced mitochondrial impairment, several isolated mitochondria- or cell line-based assays have been reported. Among them, culturing HepG2 cells in galactose provides a remarkable method to assess mitochondrial toxicity by activating mitochondrial aerobic respiration. We applied this assay to primary rat hepatocytes by culturing cells in galactose and hyperoxia to enhance the evaluation of metabolism-related drug-induced mitochondrial toxicity...
May 2, 2017: Current Protocols in Toxicology
https://www.readbyqxmd.com/read/28452943/pectic-bee-pollen-polysaccharide-from-rosa-rugosa-alleviates-diet-induced-hepatic-steatosis-and-insulin-resistance-via-induction-of-ampk-mtor-mediated-autophagy
#11
Xinzhi Li, Haiquan Gong, Siwen Yang, Lulu Yang, Yuying Fan, Yifa Zhou
Despite it is used as a nutraceutical against diabetes and obesity, the mechanism of action of bee pollen is still unclear. Pectic bee pollen polysaccharide (RBPP-P) was isolated from Rosa rugosa, and its structure was characterized by (13)C-NMR and Fourier transform-infrared spectroscopy (FT-IR). Using high glucose and fatty acids-treated HepG2 cells and high fat diet (HFD)-induced obesity mice, we detected its effect on insulin function and lipid metabolism based on autophagy. RBPP-P contained arabinogalactan, rhamnogalacturonan I, and homogalacturonan domains...
April 28, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28439947/sirt1-hsf1-hsps-pathway-is-essential-for-exenatide-alleviated-lipid-induced-hepatic-endoplasmic-reticulum-stress
#12
Xiaobin Zheng, Fen Xu, Hua Liang, Huanyi Cao, Mengyin Cai, Wen Xu, Jianping Weng
Recent studies have indicated lipid-induced endoplasmic reticulum (ER) stress to be a major contributor to the progression of hepatic steatosis. Exenatide (Exendin-4), a glucagon-like peptide-1 receptor agonist, is known to improve hepatic steatosis with accumulating evidence. In this study, we investigated whether exenatide could alleviate lipid-induced hepatic ER stress through mammal sirtuin1 (SIRT1) and illustrated the detailed mechanisms. Male C57BL/6J mice challenged with a high-fat diet (HFD) were then treated with exenatide or normal saline by intraperitoneal injection for 4 weeks...
April 25, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28436464/glucose-dependent-regulation-of-pregnane-x-receptor-is-modulated-by-amp-activated-protein-kinase
#13
Peter O Oladimeji, Wenwei Lin, C Trent Brewer, Taosheng Chen
Pregnane X receptor (PXR) is a xenobiotic receptor that regulates the detoxification and clearance of drugs and foreign compounds from the liver. There has been mounting evidence of crosstalk between the drug metabolism pathway and the energy metabolism pathway, but little is known about this cross-regulation. To further delineate the energy metabolism and drug metabolism crosstalk in this study, we exposed HepG2 cells to varying glucose concentrations. We observed that PXR activity was induced under high-glucose conditions...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28428480/exposure-to-high-glucose-concentration-decreases-cell-surface-abca1-and-hdl-biogenesis-in-hepatocytes
#14
Maki Tsujita, Mohammad Anwar Hossain, Rui Lu, Tomoe Tsuboi, Kuniko Okumura-Noji, Shinji Yokoyama
AIM: To study atherosclerosis risk in diabetes, we investigated ATP-binding cassette transporter A1 (ABCA1) expression and high-density lipoprotein (HDL) biogenesis in the liver and hepatocytes under hyperglycemic conditions. METHODS AND RESULTS: In streptozotocin-induced diabetic mice, plasma HDL decreased while ABCA1 protein increased without changing its mRNA in the liver, only in the animals that responded to the treatment to show hypoinsulinemia and fasting hyperglycemia but not in the poor responders not showing those...
April 19, 2017: Journal of Atherosclerosis and Thrombosis
https://www.readbyqxmd.com/read/28402540/the-hepatic-protection-effects-of-hepassocin-in-hyperglycemic-crisis
#15
Horng-Yih Ou, Hung-Tsung Wu, Ching-Han Lin, Ye-Fong Du, Che-Yuan Hu, Hao-Chang Hung, Pansee Wu, Hung-Yuan Li, Shu-Huei Wang, Chih-Jen Chang
CONTEXT: High glucose generates reactive oxygen species (ROS) and contributes to glucotoxicity in hepatocytes, and hyperglycemia causes structural and functional damage to the liver. However, only a mild hepatic dysfunction was observed in subjects with hyperglycemic crisis, implying a factor exists to exert a hepatic protective effect. Hepassocin is a hepatokine that modulates the proliferation and metabolism of hepatocytes, and also exerts protective activity in liver injury. However, its role in hyperglycemic crisis-induced hepatic dysfunction remains unknown...
April 11, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28393248/epigallocatechin-3-gallate-ameliorates-insulin-resistance-in-hepatocytes
#16
Shan-Bo Ma, Rui Zhang, Shan Miao, Bin Gao, Yang Lu, Sen Hui, Long Li, Xiao-Peng Shi, Ai-Dong Wen
Hyperglycemia is a typical pathogenic factor in a series of complications among patients with type II diabetes. Epigallocatechin-3-gallate (EGCG) is the major polyphenol extracted from green tea and is reported to be an antioxidant. The aim of the present study was to examine the effect of EGCG on insulin resistance in human HepG2 cells pretreated with high concentrations of glucose. The protein kinase B (AKT)/glycogen synthase kinase (GSK) pathways were analyzed using western blot analysis in HepG2 cells and primary mouse hepatocytes treated with high glucose and/or EGCG...
June 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28379184/the-effect-of-phloroglucinol-a-component-of-ecklonia-cava-extract-on-hepatic-glucose-production
#17
Ji-Young Yoon, Hojung Choi, Hee-Sook Jun
Phloroglucinol is a phenolic compound that is one of the major compounds in Ecklonia cava (brown alga). It has many pharmacological activities, but its anti-diabetic effect is not yet fully explored. In this study, we investigated the effect of phloroglucinol on the control of blood glucose levels and the regulation of hepatic glucose production. Phloroglucinol significantly improved glucose tolerance in male C57BL/6J mice fed a high fat diet (HFD) and inhibited glucose production in mouse primary hepatocytes...
April 5, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28377317/dehydroascorbate-derivatized-chitosan-particles-for-targeting-antimalarial-agents-to-infected-erythrocytes
#18
Hasham Shafi, D V Siva Reddy, Tabassum Khan, Rajeev Ranjan, Ashish Srivastava, Suniti Vaishya, Tanuj Sharma, Mohammad Imran Siddiqui, Saman Habib, Amit Misra
The mammalian glucose transporter GLUT-1 and Plasmodium falciparum hexose transporter PfHT1 are overexpressed on human RBC infected with the parasite (iRBC), presumably for enhanced glucose uptake. Dehydroascorbic acid (DHA) competes out glucose in GLUT-1 binding. We prepared particles containing chloroquine phosphate using novel derivatives of chitosan (CSN). CSN was either pre-derivatized with DHA (PRE) or particles made of CSN were derivatized by surface-grafting DHA (POST). The optimized formulations were analyzed for size (170-200nm) drug content (about 40%) entrapment efficiency (50-57%), in vitro drug release (80% in 72h, Higuchi's model), hemolysis on exposure to whole blood or RBC at 5% hematocrit, cytotoxicity towards cultured HEK 293T (kidney) and HepG2 (hepatic) cells, targeting iRBC and in vitro efficacy against P...
April 2, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28372462/polysaccharides-extraction-from-opuntia-stricta-and-their-protective-effect-against-hepg2-cell-death-and-hypolipidaemic-effects-on-hyperlipidaemia-rats-induced-by-high-fat-diet
#19
Bahira Harrabi, Khaled Athmouni, Latifa Hamdaoui, Lobna Ben Mahmoud, Ahmed Hakim, Abdelfattah El Feki, Khaled Zeghal, Hanéne Ghozzi
The aim of this study was to analyse cytoprotective effect of polysaccharides compound from Opuntia stricta (O. stricta) cladode (POS) in vitro including its radical scavenging activities and protective effects against hypercholesterolaemia. Our results showed that glucose was the dominant monosaccharides (30.35%). Arabinose, pyranose, fructose, galactose, glucose, sorbitol, S-inositol, M-inositol, trehalose and saccharose found in this species. O. stricta polysaccharides did not cause any cytotoxic effect on HepG2 cells within the range of concentrations tested (0-400 μgml(-1))...
April 3, 2017: Archives of Physiology and Biochemistry
https://www.readbyqxmd.com/read/28221022/quantitative-13-c-traces-of-glucose-fate-in-hepatitis-b-virus-infected-hepatocytes
#20
Qianfen Wan, Yulan Wang, Huiru Tang
Quantitative characterization of (13)C-labeled metabolites is an important part of the stable isotope tracing method widely used in metabolic flux analysis. Given the long relaxation time and low sensitivity of (13)C nuclei, direct measurement of (13)C-labeled metabolites using one-dimensional (13)C NMR often fails to meet the demand of metabolomics studies, especially with large numbers of samples and metabolites having low abundance. Although HSQC-based 2D NMR methods have improved sensitivity with inversion detection, they are time-consuming and thus unsuitable for high-throughput absolute quantification of (13)C-labeled metabolites...
March 6, 2017: Analytical Chemistry
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