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Kwang-Youn Kim, Hyun-Jun Jang, Yong Ryul Yang, Kwang-Il Park, JeongKon Seo, Il-Woo Shin, Tae-Il Jeon, Soon-Cheol Ahn, Pann-Ghill Suh, Timothy F Osborne, Young-Kyo Seo
Dysregulated autophagy is associated with steatosis and non-alcoholic fatty liver disease (NAFLD), however the mechanisms connecting them remain poorly understand. Here, we show that co-administration of lovastatin and ezetimibe (L/E) significantly reverses hepatic triglyceride accumulation concomitant with an increase in SREBP-2 driven autophagy in mice fed a high-fat diet (HFD). We further show that the statin mediated increase in SREBP-2 directly activates expression of patatin-like phospholipase domain-containing enzyme 8 (PNPLA8) gene, and PNPLA8 associates with autophagosomes and is associated with a decrease in cellular triglyceride...
October 21, 2016: Scientific Reports
Ru-Yue Xiao, Junjun Hao, Yi-Hong Ding, Yan-Yun Che, Xiao-Ju Zou, Bin Liang
Due to misbalanced energy surplus and expenditure, obesity has become a common chronic disorder that is highly associated with many metabolic diseases. Pu-erh tea, a traditional Chinese beverage, has been believed to have numerous health benefits, such as anti-obesity. However, the underlying mechanisms of its anti-obesity effect are yet to be understood. Here, we take the advantages of transcriptional profile by RNA sequencing (RNA-Seq) to view the global gene expression of Pu-erh tea. The model organism Caenorhabditis elegans was treated with different concentrations of Pu-erh tea water extract (PTE, 0 g/mL, 0...
October 17, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Bonglee Kim, Moon-Jea Woo, Chul-Soo Park, Sang-Hun Lee, Jin-Soo Kim, Boim Kim, Seho An, Sung-Hoon Kim
Hovenia dulcis Thunb. (HDT) was known to have anti-fatigue, anti-diabetes, neuroprotective, and hepatoprotective effects. In the present study, the anti-fatty liver mechanism of HDT was elucidated in oleic acid (OA)-treated Hep G2 cells and acute hyperlipidemia mouse model using Triton WR-1339. Here, HDT activated p-AMP-activated protein kinase (p-AMPK), proliferator activated receptor-α, carnitine palmitoyltransferase and also inhibited the expression of lipogenesis and cholesterol synthesis proteins, such as 3-hydroxy-3-methylglutaryl-CoA reductase, sterol regulatory element binding protein-1c, SREBP-2, and fatty acid synthase in OA-treated Hep G2 cells...
October 20, 2016: Phytotherapy Research: PTR
Da Zhou, Bing-Hang Li, Jing Wang, Yong-Nian Ding, Yan Dong, Yuan-Wen Chen, Jian-Gao Fan
BACKGROUND: Prolyl oligopeptidase (POP) is a serine endopeptidase that is widely distributed in vivo, particularly in the liver. Significant changes in functional mitochondrial proteins involved with mitochondrial oxidoreductases/transporters and nucleic acid binding proteins were observed after POP inhibition in the liver, which suggested a role of POP in regulating liver energy metabolism. Steatosis in nonalcoholic fatty liver disease (NAFLD) is associated with disturbances in lipid and energy metabolism in hepatocytes...
2016: PloS One
Takeshi Funakoshi, Toshihiko Aki, Masateru Tajiri, Kana Unuma, Koichi Uemura
Aberrant cellular accumulation of cholesterol is associated with neuronal lysosomal storage disorders such as Niemann-Pick disease Type C (NPC). We have shown previously that l-norephedrine (l-Nor), a sympathomimetic amine, induces necrotic cell death associated with massive cytoplasmic vacuolation in SH-SY5Y human neuroblastoma cells. To reveal the molecular mechanism underling necrotic neuronal cell death caused by l-Nor, we examined alterations in the gene expression profile of cells during l-Nor exposure...
October 18, 2016: Journal of Biological Chemistry
T Komprda, V Rozíková, N Zamazalová, O Škultéty, M Vícenová, M Trčková, M Faldyna
The objective of the present study was to compare hepatic fatty acid deposition, plasma lipid level and expression of cholesterol homeostasis controlling genes in the liver of rats (Wistar Albino; n = 32) and pigs (Large White × Landrace; n = 32) randomly assigned into two groups of 16 animals each and fed 10 weeks the diet with either 2.5% of fish oil (F; source of eicosapentaenoic and docosahexaenoic acid, EPA+DHA) or 2.5% of palm oil (P; high content of saturated fatty acids; control). F-rats deposited in the liver three times less EPA, but 1...
October 16, 2016: Journal of Animal Physiology and Animal Nutrition
Cornelia Habacher, Yanwu Guo, Richard Venz, Pooja Kumari, Anca Neagu, Dimos Gaidatzis, Eva B Harvald, Nils J Færgeman, Heinz Gut, Rafal Ciosk
Obesity is a global health issue, arousing interest in molecular mechanisms controlling fat. Transcriptional regulation of fat has received much attention, and key transcription factors involved in lipid metabolism, such as SBP-1/SREBP, LPD-2/C/EBP, and MDT-15, are conserved from nematodes to mammals. However, there is a growing awareness that lipid metabolism can also be controlled by post-transcriptional mechanisms. Here, we show that the Caenorhabditis elegans RNase, REGE-1, related to MCPIP1/Zc3h12a/Regnase-1, a key regulator of mammalian innate immunity, promotes accumulation of body fat...
October 7, 2016: Developmental Cell
Javier A Menendez, Luciano Vellon, Ingrid Espinoza, Ruth Lupu
The angiogenic inducer CCN1 (Cysteine-rich 61, CYR61) is differentially activated in metastatic breast carcinomas. However, little is known about the precise mechanisms that underlie the pro-metastatic actions of CCN1. Here, we investigated the impact of CCN1 expression on fatty acid synthase (FASN), a metabolic oncogene thought to provide cancer cells with proliferative and survival advantages. Forced expression of CCN1 in MCF-7 cells robustly up-regulated FASN protein expression and also significantly increased FASN gene promoter activity 2- to 3-fold, whereas deletion of the sterol response element-binding protein (SREBP) binding site in the FASN promoter completely abrogated CCN1-driven transcriptional activation...
2016: Oncoscience
Juwen C DuBois, A George Smulian
The Histoplasma capsulatum sterol regulatory element binding protein (SREBP), Srb1 is a member of the basic helix-loop-helix (bHLH), leucine zipper DNA binding protein family of transcription factors that possess a unique tyrosine (Y) residue instead of an arginine (R) residue in the bHLH region. We have determined that Srb1 message levels increase in a time dependent manner during growth under oxygen deprivation (hypoxia). To further understand the role of Srb1 during infection and hypoxia, we silenced the gene encoding Srb1 using RNA interference (RNAi); characterized the resulting phenotype, determined its response to hypoxia, and its ability to cause disease within an infected host...
2016: PloS One
Kristian K Jensen, Marija Tadin-Strapps, Sheng-Ping Wang, James Hubert, Yanqing Kan, Yong Ma, David G McLaren, Stephen F Previs, Kithsiri B Herath, Ablatt Mahsut, Andy Liaw, Shubing Wang, Steven J Stout, CarolAnn Keohan, Gail Forrest, David Coelho, Satya Yendluri, Stephanie Williams, Martin Koser, Steven Bartz, Karen O Akinsanya, Shirly Pinto
SREBP cleavage-activating protein (SCAP) is a key protein in the regulation of lipid metabolism and a potential target for treatment of dyslipidemia. SCAP is required for activation of the transcription factors SREBP-1 and -2. SREBPs regulate the expression of genes involved in fatty acid and cholesterol biosynthesis, and LDL-C clearance through the regulation of LDLR and PCSK9 expression. To further test the potential of SCAP as a novel target for treatment of dyslipidemia, we used short interfering RNAs (siRNA) to inhibit hepatic SCAP expression and assess the effect on PCSK9, LDLR and lipids in mice and rhesus monkeys...
October 5, 2016: Journal of Lipid Research
Jisheng Bao, Liping Zhu, Qi Zhu, Jianhua Su, Menglan Liu, Wei Huang
Re-programming of lipogenic signaling has been previously demonstrated to result in significant alterations in tumor cell pathology. Sterol regulatory element-binding protein 1 (SREBP-1) is a known transcription factor of lipogenic genes. Despite the fact that its functions in proliferation and apoptosis have been elucidated in recent studies, its role in tumor cell migration and invasion, particularly in breast cancer, remains unclear. In present study, the messenger RNA and protein expression levels of SREBP-1 in cancer tissues were observed to be overexpressed compared with those in matched para-cancerous tissues (P<0...
October 2016: Oncology Letters
Li Liu, Shang Wang, Ling Yao, Jin-Xiu Li, Peng Ma, Li-Rong Jiang, Da-Zhi Ke, Yong-Quan Pan, Jian-Wei Wang
Dietary fructose is considered a risk factor for metabolic disorders, such as fatty liver disease. However, the mechanism underlying the effects of fructose is not well characterized. We investigated the hepatic expression of key regulatory genes related to lipid metabolism following fructose feeding under well-defined conditions. Rats were fed standard chow supplemented with 10% w/v fructose solution for 5 weeks, and killed after chow-fasting and fructose withdrawal (fasting) or chow-fasting and continued fructose (fructose alone) for 14 h...
October 28, 2016: Biochemical and Biophysical Research Communications
Oren Rom, Hila Korach-Rechtman, Tony Hayek, Yael Danin-Poleg, Haim Bar, Yechezkel Kashi, Michael Aviram
The unsaturated aldehyde acrolein is pro-atherogenic, and the polyphenol-rich pomegranate juice (PJ), known for its anti-oxidative/anti-atherogenic properties, inhibits macrophage foam cell formation, the hallmark feature of early atherosclerosis. This study aimed to investigate two unexplored areas of acrolein atherogenicity: macrophage lipid metabolism and the gut microbiota composition. The protective effects of PJ against acrolein atherogenicity were also evaluated. Atherosclerotic apolipoprotein E-deficient (apoE(-/-)) mice that were fed acrolein (3 mg/kg/day) for 1 month showed significant increases in serum and aortic cholesterol, triglycerides, and lipid peroxides...
September 30, 2016: Archives of Toxicology
Luisa Pozzo, Andrea Vornoli, Ilaria Coppola, Clara Maria Della Croce, Lucia Giorgetti, Pier Giovanni Gervasi, Vincenzo Longo
AIMS: The aim of the study was to evaluate lipid, cholesterol and glucose metabolism in a novel rat model of non-alcoholic fatty liver disease (NAFLD). MAIN METHODS: Rats (Wistar) were fed high fat/cholesterol diet (HFD) and a single low dose (35mg/kg) of streptozotocin (STZ). Collagen and glycogen content, oxidative stress and glucokinase activity were measured using biochemical assays. Other metabolic pathway were assessed by qRT-PCR. KEY FINDINGS: HFD/STZ treated rats, compared to control ones, showed an increase in expression of biomarkers of inflammation (TNFα, IL6), fibrosis (TGFβ), mitochondrial stress (UCP2) and oxidative stress (GSH and carbonylated proteins) but not of ER stress (CHOP, XBP1)...
September 28, 2016: Life Sciences
Mark F McCarty
In type 1 diabetics, hepatic exposure to insulin is chronically subnormal even in the context of insulin therapy; as a result, expression of glycolytic enzymes is decreased, and that of gluconeogenic enzymes is enhanced, resulting in a physiologically inappropriate elevation of hepatic glucose output. Subnormal expression of glucokinase (GK) is of particular importance in this regard. Possible strategies for correcting this perturbation of hepatic enzyme expression include administration of small molecule allosteric activators of GK, as well as a procedure known as chronic intermittent intravenous insulin therapy (CIIIT); however, side effects accompany the use of GK activators, and CIIIT is time and labor intensive...
October 2016: Medical Hypotheses
Sayaka Nomura, Kaori Endo-Umeda, Makoto Makishima, Yuichi Hashimoto, Minoru Ishikawa
Liver X receptor (LXR) agonists are candidates for the treatment of atherosclerosis via induction of ABCA1 (ATP-binding cassette A1) gene expression, which contributes to reverse cholesterol transport (RCT) and to cholesterol efflux from the liver and intestine. However, LXR agonists also induce genes involved in lipogenesis, such as SREBP-1c (sterol regulatory binding element protein 1c) and FAS (fatty acid synthase), thereby causing an undesirable increase in plasma and hepatic triglyceride (TG) levels...
September 30, 2016: ChemMedChem
Tingxian Deng, Chunying Pang, Xiaoya Ma, Xingrong Lu, Anqin Duan, Peng Zhu, Xianwei Liang
Insulin-induced genes (INSIGs), including INSIG1 and INSIG2, are important mediators that play a pivotal role in the lipid metabolism and could cause the retention of the SCAP/SREBP complex. Therefore, the objective of this study is to detect the single nucleotide polymorphisms (SNPs) of buffalo INSIG2 gene and evaluate their associations with milk production traits in Chinese buffaloes. A total of four SNPs (g.621272A > G, g.621364A > C, g.632543G > A, and g.632684C > T) were identified using DNA pooled sequencing, and the SNP genotyping for the identified SNPs was performed by using Matrix-assisted laser desorption/ionization time of flight mass spectrometry method from 264 individuals...
September 27, 2016: Molecular and Cellular Probes
Donghee Kim, Song Mi Lee, Hee-Sook Jun
Type 1 diabetes results from autoimmune-mediated pancreatic beta cell destruction and TGF-β is known to play a preventive role in type 1 diabetes in non-obese diabetic (NOD) mice. In this study, we investigated the role of Smad4, a key molecule for Smad-dependent TGF-β signaling, in T cells of NOD mice in the pathogenesis of autoimmune diabetes. We generated T cell-specific Smad4 knockout (Smad4 tKO) NOD mice and assessed the pathological and immunological changes. Smad4 tKO showed earlier onset and increased incidence of diabetes than wild-type (WT) NOD mice...
September 30, 2016: Immunology and Cell Biology
Kalathookunnel Antony Antu, Mariam Philip Riya, Anupama Nair, Arvind Mishra, Arvind K Srivastava, Kozhiparambil Gopalan Raghu
ETHNOPHARMACOLOGICAL RELEVANCE: This plant has been utilized in Indian system of medicine for treatment of diabetes. This is clearly evident from the composition of Ayurvedic preparation for diabetes 'Nisakathakadi Kashayam' where this is one of the main ingredients of this preparation. AIM OF THE STUDY: The study aims in elucidating the molecular mechanisms underlying the insulin sensitizing effects of Symplocos cochinchinensis ethanol extract (SCE) using a high fructose and saturated fat (HFS) fed insulin resistant rat model...
September 26, 2016: Journal of Ethnopharmacology
Alisson L da Rocha, Ana P Pinto, Giovana R Teixeira, Bruno C Pereira, Luciana C Oliveira, Adriana C Silva, Gustavo P Morais, Dennys E Cintra, José R Pauli, Adelino S R da Silva
Recently, we demonstrated that an overtraining (OT) protocol for mice based on downhill running sessions increased the hepatic phosphorylation of 70-kDa ribosomal protein S6 kinase 1 (S6K1; Thr389), a downstream target of the mammalian target of rapamycin complex 1 (mTORC1). In liver, the overactivation of the Akt/mTORC1 pathway induces lipogenesis via regulation of the action of sterol regulatory element binding protein-1 (SREBP-1) at multiple steps. Herein, we verified the effects of three running OT models with same external load (i...
September 29, 2016: Journal of Cellular Physiology
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