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https://www.readbyqxmd.com/read/28645614/site-1-protease-a-novel-metabolic-target-for-glioblastoma
#1
Beth T Caruana, Aleksandra Skoric, Andrew J Brown, Louise H Lutze-Mann
Sterol regulatory element binding proteins (SREBPs) are transcriptional regulators of lipids which promote glioblastoma growth. Here, we investigate the effect of inhibiting expression of SREBP target genes in human glioblastoma cells. This was achieved by using PF-429242 to inhibit site-1 protease (S1P), an enzyme required for SREBP activation. Treatment with PF-429242 decreased glioblastoma cell viability, induced apoptosis and downregulated steroid, isoprenoid and unsaturated fatty acid biosynthetic pathways...
June 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28643888/combination-of-citrus-polymethoxyflavones-green-tea-polyphenols-and-lychee-extracts-suppresses-obesity-and-hepatic-steatosis-in-high-fat-diet-induced-obese-mice
#2
Min-Hsiung Pan, Guliang Yang, Shiming Li, Ming-Yi Li, Mei-Ling Tsai, Jia-Ching Wu, Vladimir Badmaev, Chi-Tang Ho, Ching-Shu Lai
SCOPE: SlimTrym(®) is a formulated product composed of citrus polymethoxyflavones (PMFs), green tea extract and lychee extract. We investigated the effect of dietary SlimTrym(®) on diet-induced obesity and associated non-alcoholic fatty liver disease (NAFLD) in mice. METHODS AND RESULTS: Male C57BL/6 mice were fed a normal diet (ND), high fat diet (HFD) or HFD containing 0.1% or 0.5% SlimTrym(®) for sixteen weeks. Dietary SlimTrym(®) significantly reduced weight gain and relative perigonadal, retroperitoneal, mesenteric fat weight as well as the size of adipocyte in HFD-fed mice...
June 23, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28639266/bakuchiol-contributes-to-the-hepatotoxicity-of-psoralea-corylifolia-in-rats
#3
Zhi-Jian Li, Abudumijiti Abulizi, Guo-Lin Zhao, Tao Wang, Fan Zhou, Zhen-Zhou Jiang, Silafu Aibai, Lu-Yong Zhang
Psoralea corylifolia L. (Fructus Psoraleae) is widely used in Asia, but there are concerns about hepatotoxicity caused by constituents such as psoralens and bakukiol. Bakuchiol (BAK) has antiinflammatory, antipyretic, antibacterial antiviral, anticancer, and estrogenic activity but appears to be hepatotoxic in in vitro tests. This study investigated the hepatotoxicity in vivo in rats. Using intragastrically administered bakuchiol at doses of 52.5 and 262.5 mg/kg for 6 weeks. Bodyweight, relative liver weight, biochemical indicators, histopathology, mRNA expression of CYP7A1, HMG-CoA reductase, BSEP, PPARα, SREBP-2, and MRP3 were measured...
June 22, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28635324/gliptins-suppress-inflammatory-macrophage-activation-to-mitigate-inflammation-fibrosis-oxidative-stress-and-vascular-dysfunction-in-models-of-non-alcoholic-steatohepatitis-and-liver-fibrosis
#4
Xiaoyu Wang, Michael Hausding, Shih-Yen Weng, Yong Ook Kim, Sebastian Steven, Thomas Klein, Andreas Daiber, Detlef Schuppan
AIMS: Non-alcoholic steatohepatitis (NASH) is characterized by steatosis, panlobular inflammation, liver fibrosis and increased cardiovascular mortality. Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) are indirect glucagon like peptide 1 (GLP-1) agonists with antidiabetic and anti-inflammatory activity, used for the treatment of type 2 diabetes. Their potential and underlying mechanisms to treat metabolic liver inflammation and fibrosis as well as the associated vascular dysfunction remain to be explored...
June 21, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28630260/cholesterol-auxotrophy-and-intolerance-to-ezetimibe-in-mice-with-srebp-2-deficiency-in-the-intestine
#5
Shunxing Rong, Jeffrey McDonald, Luke Engelking
Sterol regulatory element-binding protein-2 (SREBP-2) activates transcription of all genes needed for cholesterol biosynthesis. To study SREBP-2 function in intestine, we generated a mouse model (Vil-BP2(-/-) ) in which Cre recombinase ablates SREBP-2 in intestinal epithelia. Intestines of Vil-BP2(-/-) mice had reduced expression of genes required for sterol synthesis, in vivo sterol synthesis rates, and epithelial cholesterol contents. On a cholesterol-free diet, they displayed chronic enteropathy with histological abnormalities of both villi and crypts, growth restriction, and reduced survival that was prevented by supplementation of cholesterol in the diet...
June 19, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28628909/nonalcoholic-fatty-liver-disease-impairs-the-cytochrome-p-450-dependent-metabolism-of-%C3%AE-tocopherol-vitamin-e
#6
Desirée Bartolini, Pierangelo Torquato, Carolina Barola, Angelo Russo, Chiara Rychlicki, Danilo Giusepponi, Guido Bellezza, Angelo Sidoni, Roberta Galarini, Gianluca Svegliati-Baroni, Francesco Galli
This study aims to investigate in in vivo and in vitro models of nonalcoholic fatty liver disease (NAFLD) the enzymatic metabolism of α-tocopherol (vitamin E) and its relationship to vitamin E-responsive genes with key role in the lipid metabolism and detoxification of the liver. The experimental models included mice fed a high-fat diet combined or not with fructose (HFD+F) and HepG2 human hepatocarcinoma cells treated with the lipogenic agents palmitate, oleate or fructose. CYP4F2 protein, a cytochrome P-450 isoform with proposed α-tocopherol ω-hydroxylase activity, decreased in HFD and even more in HFD+F mice liver; this finding was associated with increased hepatic levels of α-tocopherol and decreased formation of the corresponding long-chain metabolites α-13-hydroxy and α-13-carboxy chromanols...
June 7, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28617309/lipid-storage-and-autophagy-in-melanoma-cancer-cells
#7
Claudia Giampietri, Simonetta Petrungaro, Martina Cordella, Claudio Tabolacci, Luana Tomaipitinca, Antonio Facchiano, Adriana Eramo, Antonio Filippini, Francesco Facchiano, Elio Ziparo
Cancer stem cells (CSC) represent a key cellular subpopulation controlling biological features such as cancer progression in all cancer types. By using melanospheres established from human melanoma patients, we compared less differentiated melanosphere-derived CSC to differentiating melanosphere-derived cells. Increased lipid uptake was found in melanosphere-derived CSC vs. differentiating melanosphere-derived cells, paralleled by strong expression of lipogenic factors Sterol Regulatory Element-Binding Protein-1 (SREBP-1) and Peroxisome Proliferator-Activated Receptor-γ (PPAR-γ)...
June 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28612527/-the-effect-of-p-jak1-p-stat3-signaling-way-in-intervening-nafld-by-blueberry-probiotic-serum
#8
Juan-Juan Zhu, Ming-Liang Cheng, Ming-Yu Zhou, Xue-Ke Zhao
OBJECTIVES: To explore the mechanism of interlukin-22 (IL-22)-mediated phosphor-Janus kinase-1(p-JAK1)/phosphor-signal transducer and activator of transcription 3 (p-STAT3) signaling way in the experiment of improving non-alcholic fatty liver disease (NAFLD) by blueberry probiotic serum. METHODS: The rat serums with low-, medium-, and high-dose of 10% blueberry probiotics, as well as saline were prepared. NAFLD model was built by inducing normal liver cell line L-02 with free fatty acid (FFA)...
March 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28607088/skin-specific-regulation-of-srebp-processing-and-lipid-biosynthesis-by-glycerol-kinase-5
#9
Duanwu Zhang, Wataru Tomisato, Lijing Su, Lei Sun, Jin Huk Choi, Zhao Zhang, Kuan-Wen Wang, Xiaoming Zhan, Mihwa Choi, Xiaohong Li, Miao Tang, Jose M Castro-Perez, Sara Hildebrand, Anne R Murray, Eva Marie Y Moresco, Bruce Beutler
The recessive N-ethyl-N-nitrosourea-induced phenotype toku is characterized by delayed hair growth, progressive hair loss, and excessive accumulation of dermal cholesterol, triglycerides, and ceramides. The toku phenotype was attributed to a null allele of Gk5, encoding glycerol kinase 5 (GK5), a skin-specific kinase expressed predominantly in sebaceous glands. GK5 formed a complex with the sterol regulatory element-binding proteins (SREBPs) through their C-terminal regulatory domains, inhibiting SREBP processing and activation...
June 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28591582/hepatocyte-abca1-deletion-impairs-liver-insulin-signaling-and-lipogenesis
#10
Chia-Chi C Key, Mingxia Liu, C Lisa Kurtz, Soonkyu Chung, Elena Boudyguina, Timothy A Dinh, Alexander Bashore, Peter E Phelan, Barry I Freedman, Timothy F Osborne, Xuewei Zhu, Lijun Ma, Praveen Sethupathy, Sudha B Biddinger, John S Parks
Plasma membrane (PM) free cholesterol (FC) is emerging as an important modulator of signal transduction. Here, we show that hepatocyte-specific knockout (HSKO) of the cellular FC exporter, ATP-binding cassette transporter A1 (ABCA1), leads to decreased PM FC content and defective trafficking of lysosomal FC to the PM. Compared with controls, chow-fed HSKO mice had reduced hepatic (1) insulin-stimulated Akt phosphorylation, (2) activation of the lipogenic transcription factor Sterol Regulatory Element Binding Protein (SREBP)-1c, and (3) lipogenic gene expression...
June 6, 2017: Cell Reports
https://www.readbyqxmd.com/read/28587208/xyloketal-b-attenuates-fatty-acid-induced-lipid-accumulation-via-the-srebp-1c-pathway-in-nafld-models
#11
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/28585425/cide-gene-expression-in-adipose-tissue-liver-and-skeletal-muscle-from-obese-and-lean-pigs
#12
Yue-Qin Qiu, Xue-Fen Yang, Xian-Yong Ma, Yun-Xia Xiong, Zhi-Mei Tian, Qiu-Li Fan, Li Wang, Zong-Yong Jiang
The expression of the cell death-inducing DNA fragmentation factor α-like effector (CIDE) family including Cidea, Cideb, and Cidec was significantly increased in mouse and human models of obesity. However, there was less information on these genes' expression in pigs. Here, we hypothesized that different fat accumulation between lean (Duroc×Landrace×Yorkshire gilts, DLY) and obese (Lantang) pigs was attributed to porcine CIDE-modulating lipid metabolism. Our data showed that Cidea and Cidec were expressed at a high level in adipose tissue, and at a relatively high level in skeletal muscle, whereas Cideb was mainly expressed in the liver in both breeds of pig...
June 2017: Journal of Zhejiang University. Science. B
https://www.readbyqxmd.com/read/28584269/time-dependent-changes-and-potential-mechanisms-of-glucose-lipid-metabolic-disorders-associated-with-chronic-clozapine-or-olanzapine-treatment-in-rats
#13
Xuemei Liu, Zhixiang Wu, Jiamei Lian, Chang-Hua Hu, Xu-Feng Huang, Chao Deng
Chronic treatment with second-generation antipsychotic drugs (SGAs) has been associated with an increased risk of metabolic syndrome. To evaluate the longitudinal changes in glucose-lipid homeostasis after SGA use, we studied the time-dependent effects of olanzapine (OLZ) (3 mg/kg, b.i.d.) or clozapine (CLZ) (20 mg/kg, b.i.d.) treatment on metabolic profiles for 9 weeks in rats. Although only OLZ significantly increased body weight in rats, both OLZ and CLZ elevated blood lipid levels. Chronic OLZ treatment induced significant weight gain leading to a higher fasting insulin level and impaired glucose tolerance, whereas CLZ lowered fasting insulin levels and impaired glucose tolerance independent of weight gain...
June 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28579594/exploration-of-underlying-mechanism-of-anti-adipogenic-activity-of-sulfuretin
#14
Ramakanta Lamichhane, Se-Gun Kim, Sona Kang, Kyung-Hee Lee, Prakash Raj Pandeya, Hyun-Ju Jung
Sulfuretin is a natural flavonoid found in the plant Rhus verniciflua Stokes. The plant has been traditionally used as medicinal agent for antiviral, cathartic, diaphoretic, anti-rheumatic and sedative activities in East Asia. In this study we isolated and identified sulfuretin from R. verniciflua and investigated its anti-adipogenic activity against 3T3-L1 preadipocytes cells. We evaluated the effects of sulfuretin on the adipogenic transcription factors like PPARγ, C/EBPα, FAS, Fabp4, adiponectin and Zfp521 by gene expression (real-time QPCR) and Western blot analysis...
June 3, 2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28577437/rutin-exhibits-hepatoprotective-effects-in-a-mouse-model-of-non-alcoholic-fatty-liver-disease-by-reducing-hepatic-lipid-levels-and-mitigating-lipid-induced-oxidative-injuries
#15
Qingsheng Liu, Ran Pan, Lei Ding, Fuli Zhang, Linfeng Hu, Bin Ding, Linwensi Zhu, Yongliang Xia, Xiaobing Dou
Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive accumulation of hepatic lipids and oxidative injury of hepatocytes. Rutin is a natural flavonoid with significant roles in combating cellular oxidative stress and regulating lipid metabolism. The current study aims to investigate the molecular mechanisms underlying rutin's hypolipidemic and hepatoprotective effects in nonalcoholic fatty liver disease. Rutin treatment was applied to male C57BL/6 mice maintained on a high-fat diet and HepG2 cells challenged with oleic acid...
May 31, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28557705/moringa-olifeira-lam-stimulates-activation-of-the-insulin-dependent-akt-pathway-antidiabetic-effect-in-a-diet-induced-obesity-dio-mouse-model
#16
E S Attakpa, M M Sangaré, G J Béhanzin, J-M Ategbo, B Seri, N A Khan
We investigated the antidiabetic effect of Moringa olifeira Lam. in a diet-induced obesity (DIO) mouse model. Six mice were randomly selected as normal controls. Moringa olifeira Lam. leaf extract at a dose of 200, 400 or 600 mg/kg body weight, glibenclamide (Glib) at the dose of 10 mg/kg (positive control) and distilled water at 10 ml/kg (control group) were administered orally by gastric intubation, and each group consisted of six mice. Insulinsensitive tissues (liver, skeletal muscle) were collected to investigate antidiabetic effects and examine the plant's molecular mechanisms...
2017: Folia Biologica (Praha)
https://www.readbyqxmd.com/read/28557334/pleiotrophin-a-target-of-mir-384-promotes-proliferation-metastasis-and-lipogenesis-in-hbv-related-hepatocellular-carcinoma
#17
Pei-Song Bai, Nan Xia, Hong Sun, Ying Kong
Hepatitis B virus (HBV) infection plays a crucial role and is a major cause of hepatocellular carcinoma (HCC) in China. microRNAs (miRNAs) have emerged as key players in hepatic steatosis and carcinogenesis. We found that down-regulation of miR-384 expression was a common event in HCC, especially HBV-related HCC. However, the possible function of miR-384 in HBV-related HCC remains unclear. The oncogene pleiotrophin (PTN) was a target of miR-384. HBx inhibited miR-384, increasing PTN expression. The PTN receptor N-syndecan was highly expressed in HCC...
May 30, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28554582/geranylgeraniol-prevents-the-simvastatin-induced-pcsk9-expression-role-of-the-small-g-protein-rac1
#18
Nicola Ferri, Silvia Marchianò, Maria Giovanna Lupo, Annalisa Trenti, Giuseppe Biondo, Paola Castaldello, Alberto Corsini
Statins are known to increase the plasma levels of proprotein convertase subtilisin kexin type 9 (PCSK9) through the activation of the sterol responsive element binding protein (SREBP) pathway due to the inhibition of cholesterol biosynthesis. In the present study, we explore a possible role of the prenylated proteins on the statin-mediated PCSK9 induction in Caco-2 cells. Simvastatin (40μM) induced both PCSK9 mRNA (10.7±3.2 fold) and protein (2.2±0.3 fold), after 24h incubation. The induction of PCSK9 mRNA was partially, but significantly, prevented by the co-incubation with mevalonate (MVA), farnesol (FOH) and geranylgeraniol (GGOH), while a complete prevention was observed on secreted PCSK9, evaluated by ELISA assay...
May 26, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28550454/oncogenic-roles-of-the-pi3k-akt-mtor-axis
#19
Masahiro Aoki, Teruaki Fujishita
The PI3K/AKT/mTOR pathway is frequently activated in various human cancers and has been considered a promising therapeutic target. Many of the positive regulators of the PI3K/AKT/mTOR axis, including the catalytic (p110α) and regulatory (p85α), of class IA PI3K, AKT, RHEB, mTOR, and eIF4E, possess oncogenic potentials, as demonstrated by transformation assays in vitro and by genetically engineered mouse models in vivo. Genetic evidences also indicate their roles in malignancies induced by activation of the upstream oncoproteins including receptor tyrosine kinases and RAS and those induced by the loss of the negative regulators of the PI3K/AKT/mTOR pathway such as PTEN, TSC1/2, LKB1, and PIPP...
May 28, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28549068/oligodendroglial-myelination-requires-astrocyte-derived-lipids
#20
Nutabi Camargo, Andrea Goudriaan, Anne-Lieke F van Deijk, Willem M Otte, Jos F Brouwers, Hans Lodder, David H Gutmann, Klaus-Armin Nave, Rick M Dijkhuizen, Huibert D Mansvelder, Roman Chrast, August B Smit, Mark H G Verheijen
In the vertebrate nervous system, myelination of axons for rapid impulse propagation requires the synthesis of large amounts of lipids and proteins by oligodendrocytes and Schwann cells. Myelin membranes are thought to be cell-autonomously assembled by these axon-associated glial cells. Here, we report the surprising finding that in normal brain development, a substantial fraction of the lipids incorporated into central nervous system (CNS) myelin are contributed by astrocytes. The oligodendrocyte-specific inactivation of sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP), an essential coactivator of the transcription factor SREBP and thus of lipid biosynthesis, resulted in significantly retarded CNS myelination; however, myelin appeared normal at 3 months of age...
May 2017: PLoS Biology
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