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https://www.readbyqxmd.com/read/28550454/oncogenic-roles-of-the-pi3k-akt-mtor-axis
#1
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
#2
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
https://www.readbyqxmd.com/read/28542467/genetic-variations-in-sterol-regulatory-element-binding-protein-cleavage-activating-protein-scap-are-associated-with-blood-pressure-in-overweight-obese-chinese-children
#3
Yi-De Yang, Jie-Yun Song, Shuo Wang, Fang-Hong Liu, Yi-Ning Zhang, Xiao-Rui Shang, Hai-Jun Wang, Jun Ma
OBJECTIVE: Previous studies demonstrated a role of variations in sterol regulatory element binding protein (SREBP) cleavage-activating protein (SCAP) in obesity and blood lipids. But the associations between SCAP polymorphisms and blood pressure (BP) are not clear. This study aimed to investigate the relationship between genetic variations in SCAP and BP phenotypes in a Chinese pediatric population. METHODS: A case-control study on 702 high blood pressure (HBP) children and 1319 controls was conducted to explore the correlation between single nucleotide polymorphism markers (rs12487736 and rs12490383) of SCAP and BP phenotypes...
2017: PloS One
https://www.readbyqxmd.com/read/28539336/nutritional-regulation-of-renal-lipogenic-factor-expression-in-mice-comparison-to-regulation-in-the-liver-and-skeletal-muscle
#4
Suk-Jeong Kim, Ji-Eun Kim, Yong-Woon Kim, Jong-Yeon Kim, So-Young Park
Regulation of lipogenesis by pathophysiological factors in the liver and skeletal muscle is well understood; however, regulation in the kidney is still unclear. To elucidate nutritional regulation of lipogenic factors in the kidney, we measured the renal expression of lipogenic transcriptional factors and enzymes during fasting and refeeding in chow-fed and high-fat-fed mice. We also examined the regulatory effect of the liver X receptor (LXR) on the expression of lipogenic factors. The renal gene expression of sterol regulatory element-binding protein (SREBP)-1c and fatty acid synthase (FAS) was reduced by fasting for 48 h and restored by refeeding, whereas the mRNA levels of forkhead box O (FOXO)1/3 were increased by fasting and restored by refeeding...
May 24, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28536436/functional-characterization-and-differential-nutritional-regulation-of-putative-elovl5-and-elovl4-elongases-in-large-yellow-croaker-larimichthys-crocea
#5
Songlin Li, Óscar Monroig, Tianjiao Wang, Yuhui Yuan, Juan Carlos Navarro, Francisco Hontoria, Kai Liao, Douglas R Tocher, Kangsen Mai, Wei Xu, Qinghui Ai
In the present study, two elongases, Elovl4 and Elovl5, were functionally characterized and their transcriptional regulation in response to n-3 LC-PUFA administration were investigated in vivo and in vitro. We previously described the molecular characterization of croaker elovl5. Here, we report the full-length cDNA sequence of croaker elovl4, which contained 1794 bp (excluding the polyA tail), including 909 bp of coding region that encoded a polypeptide of 302 amino acids possessing all the characteristic features of Elovl proteins...
May 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28526339/magnesium-isoglycyrrhizinate-blocks-fructose-induced-hepatic-nf-%C3%AE%C2%BAb-nlrp3-inflammasome-activation-and-lipid-metabolism-disorder
#6
Xiao-Juan Zhao, Yan-Zi Yang, Yan-Jing Zheng, Shan-Chun Wang, Hong-Mei Gu, Ying Pan, Shui-Juan Wang, Hong-Jiang Xu, Ling-Dong Kong
Magnesium isoglycyrrhizinate as a hepatoprotective agent possesses immune modulation and anti-inflammation, and treats liver diseases. But its effects on immunological-inflammatory and metabolic profiles for metabolic syndrome with liver injury and underlying potential mechanisms are not fully understood. In this study, magnesium isoglycyrrhizinate alleviated liver inflammation and lipid accumulation in fructose-fed rats with metabolic syndrome. It also suppressed hepatic inflammatory signaling activation by reducing protein levels of phosphorylation of nuclear factor-kappa B p65 (p-NF-κB p65), inhibitor of nuclear factor kappa-B kinase α/β (p-IKKα/β) and inhibitor of NF-κB α (p-IκBα) as well as nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC) and Caspase-1 in rats, being consistent with its reduction of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and IL-6 levels...
May 16, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28521874/sirna-mediated-inhibition-of-srebp-cleavage-activating-protein-reduces-dyslipidemia-in-spontaneously-dysmetabolic-rhesus-monkeys
#7
Beth Ann Murphy, Marija Tadin-Strapps, Kristian Jensen, Robin Mogg, Andy Liaw, Kithsiri Herath, Gowri Bhat, David G McLaren, Stephen F Previs, Shirly Pinto
BACKGROUND: SREBP cleavage-activating protein (SCAP) is a cholesterol binding endoplasmic reticulum (ER) membrane protein that is required to activate SREBP transcription factors. SREBPs regulate genes involved in lipid biosynthesis. They also influence lipid clearance by modulating the expression of LDL receptor (LDLR) and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. Inhibiting SCAP decreases circulating PCSK9, triglycerides (TG), and LDL-cholesterol (LDL-C), both in vitro and in vivo...
June 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28521289/role-of-transgelin-2-in-diabetes-associated-pancreatic-ductal-adenocarcinoma
#8
Yan Sun, Weiwei He, Man Luo, Yuhong Zhou, Guilin Chang, Weiying Ren, Kefen Wu, Xi Li, Jiping Shen, Xiaoping Zhao, Yu Hu
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor prognosis. Diabetes is a significant risk factor for PDAC and >50% of PDAC patients have concomitant diabetes. How diabetes influences the initiation and progression of PDAC remains elusive. Here, we show that transgelin-2 is dominantly expressed in PDAC tissues compared with adjacent normal tissues. The high level of transgelin-2 indicates poor survival of patients with PDAC. Remarkably, transgelin-2 expression is correlated with diabetic status...
April 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28514904/effects-of-viola-mandshurica-on-atherosclerosis-and-hepatic-steatosis-in-apoe-formula-see-text-via-the-ampk-pathway
#9
Sun Haeng Park, Yoon-Young Sung, Kyoung Jin Nho, Dong Sun Kim, Ho Kyoung Kim
Atherosclerosis was previously thought to be a disease that primarily involves lipid accumulation in the arterial wall. In this report, we investigated the effect of Viola mandshurica W. Becker (V. mandshurica) water extract on atherosclerosis in apolipoprotein E deficient (ApoE[Formula: see text]) mice. The administration of V. mandshurica to high-fat diet-fed mice reduced body weight, liver weight, and serum levels of lipids (total cholesterol, low-density lipoprotein-cholesterol, triglycerides), glucose, alanine transaminase, and aspartate transaminase...
May 18, 2017: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/28514835/genistein-has-beneficial-effects-on-hepatic-steatosis-in-high-fat-high-sucrose-diet-treated-rats
#10
Huanhuan Liu, Huijia Zhong, Yimin Yin, Zhuoqin Jiang
Genistein, a kind of phytoestrogen abundant in soybeans, is beneficial for alleviating non-alcoholic fatty liver disease (NAFLD), but the specific mechanism was not clearly understood. This study was designed to determine the effect of genistein on NAFLD and explore the possible mechanism. 36 male Sprague-Dawley rats were divided into 4 groups: the control group, high fat-high sucrose diet (HFS) group, HFS with 4mg/kg body weight genistein, and HFS with 8mg/kg body weight genistein. 12 weeks later, serum and hepatic lipid profiles, liver histopathological examination were characterized...
May 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28508539/the-effect-of-maternal-obesity-on-fatty-acid-transporter-expression-and-lipid-metabolism-in-the-full-term-placenta-of-lean-breed-swine
#11
L Tian, S S Dong, J Hu, J J Yao, P S Yan
This study was conducted to evaluate the influence of back-fat thickness (BF), at mating of sows, on the maternal and newborn circulating lipids, expression of placental fatty acids (FA) transporters and lipid accumulation in placenta. Full-term placentas were obtained by vaginal delivery from BFI (9-14 mm; n = 37), BFII (15-19 mm; n = 43) and BFIII (20-27 mm; n = 38) sows according to BF at mating, and frozen placental sections were analysed for fat accumulation. Blood samples were collected from the sows of day 105 pregnancy and from cord blood at delivery...
May 15, 2017: Journal of Animal Physiology and Animal Nutrition
https://www.readbyqxmd.com/read/28507477/enzymatic-hydrolysate-from-velvet-antler-suppresses-adipogenesis-in-3t3-l1-cells-and-attenuates-obesity-in-high-fat-diet-fed-mice
#12
Yuling Ding, Yanmei Wang, Byong-Tae Jeon, Sang-Ho Moon, Seung-Hong Lee
The purpose of the current study was to investigate the potential anti-obesity activity of an enzymatic hydrolysate of velvet antler in inhibiting adipogenesis in 3T3-L1 cells and in high-fat diet (HFD)-fed obese mice. The enzymatic hydrolysate was prepared using the commercial food grade protease, Protamex. The velvet antler Protamex hydrolysate (VAPH) indicated profound inhibitory effects on adipogenesis dose-dependently by decreasing the accumulation of triglycerides and down-regulating expression levels of adipogenesis-related proteins C/EBPα, SREBP-1, and PPARγ...
2017: EXCLI journal
https://www.readbyqxmd.com/read/28507114/antiviral-activity-of-nordihydroguaiaretic-acid-and-its-derivative-tetra-o-methyl-nordihydroguaiaretic-acid-against-west-nile-virus-and-zika-virus
#13
Teresa Merino-Ramos, Nereida Jiménez de Oya, Juan-Carlos Saiz, Miguel A Martín-Acebes
Flaviviruses are positive strand RNA viruses distributed all over the world that infect millions of people every year, and for which no specific antiviral agents have been approved. These viruses include the mosquito-borne West Nile virus (WNV) responsible for outbreaks of meningitis and encephalitis. Considering that nordihydroguaiaretic acid (NDGA) has been previously shown to inhibit the multiplication of the related dengue virus and hepatitis C virus, we have evaluated the effect of NDGA, and its methylated derivative tetra-O-methyl nordihydroguaiaretic (M4N), on the infection of WNV...
May 15, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28501578/anhydroicaritin-a-srebps-inhibitor-inhibits-rankl-induced-osteoclastic-differentiation-and-improves-diabetic-osteoporosis-in-stz-induced-mice
#14
Zu-Guo Zheng, Xin Zhang, Ya-Ping Zhou, Chong Lu, Pyone Myat Thu, Cheng Qian, Mu Zhang, Ping Li, Hui-Jun Li, Xiaojun Xu
Nowadays, more and more attention has been paid to osteoporosis caused by diabetes mellitus. Elevated levels of pro-inflammatory cytokines in diabetic patients activate the activity of osteoclasts through the RANKL/OPG pathway. The nuclear transcription factor SREBP2, a master regulator of cholesterol metabolism, has been found involved in osteoclastogenesis. In previous study, we have identified anhydroicaritin as a potent inhibitor of transcription factor SREBPs, which improve dyslipidemia and insulin resistance...
May 10, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28496395/a-relative-quantitative-positive-negative-ion-switching-method-for-untargeted-lipidomics-via-high-resolution-lc-ms-ms-from-any-biological-source
#15
Susanne B Breitkopf, Stéphane J H Ricoult, Min Yuan, Ying Xu, David A Peake, Brendan D Manning, John M Asara
INTRODUCTION: Advances in high-resolution mass spectrometry have created renewed interest for studying global lipid biochemistry in disease and biological systems. OBJECTIVES: Here, we present an untargeted 30 min. LC-MS/MS platform that utilizes positive/negative polarity switching to perform unbiased data dependent acquisitions (DDA) via higher energy collisional dissociation (HCD) fragmentation to profile more than 1000-1500 lipid ions mainly from methyl-tert-butyl ether (MTBE) or chloroform:methanol extractions...
March 2017: Metabolomics: Official Journal of the Metabolomic Society
https://www.readbyqxmd.com/read/28492976/squalene-promotes-cholesterol-homeostasis-in-macrophage-and-hepatocyte-cells-via-activation-of-liver-x-receptor-lxr-%C3%AE-and-%C3%AE
#16
Hoang Thi Minh Hien, Nguyen Cam Ha, Le Thi Thom, Dang Diem Hong
OBJECTIVE: To examine the effect of squalene on liver X receptors (LXRs) that regulate target genes associated with reverse cholesterol transport and thus control whole-body cholesterol homeostasis. RESULTS: To examine the effect of squalene on liver X receptors (LXRs) that regulate target genes associated with reverse cholesterol transport and thus control whole-body cholesterol homeostasis. Squalene significantly stimulated the transactivation of liver X receptor modulator LXRα and LXRβ...
May 10, 2017: Biotechnology Letters
https://www.readbyqxmd.com/read/28491104/effect-of-tetramethylpyrazine-on-atherosclerosis-and-scap-srebp-1c-signaling-pathway-in-apoe-mice-fed-with-a-high-fat-diet
#17
Ying Zhang, Pan Ren, Qunfu Kang, Weihong Liu, Sinai Li, Ping Li, Hongxu Liu, Juju Shang, Lei Zhang, Yanbing Gong, Mingxue Zhou
Lipid metabolism dysregulation plays a crucial role in the occurrence of atherosclerosis (As). SCAP/SREBP signaling is the main pathway for regulating lipid metabolism. Tetramethylpyrazine (TMP), a Traditional Chinese Medicine (TCM) for treating angina pectoris, has antiatherosclerotic effects and ameliorates blood lipids disturbance. However, its precise mechanism remains unclear. This study investigated the mechanism of TMP in ameliorating As in mice model. After six weeks of high-fat diet, 30 ApoE(-/-) mice were randomized (n = 10) and treated with Lipitor, TMP, or distilled water for six weeks...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28490610/mechanisms-of-insulin-resistance-in-primary-and-secondary-non-alcoholic-fatty-liver
#18
Tomas Jelenik, Kirti Kaul, Gilles Séquaris, Ulrich Flögel, Esther Phielix, Jörg Kotzka, Birgit Knebel, Pia Fahlbusch, Tina Hörbelt, Stefan Lehr, Anna Lena Reinbeck, Dirk Müller-Wieland, Irene Esposito, Gerald I Shulman, Julia Szendroedi, Michael Roden
Non-alcoholic fatty liver disease (NAFLD) is associated with hepatic insulin resistance and may result primarily from increased hepatic de novo lipogenesis (PRIM) or secondarily from adipose-tissue lipolysis (SEC). We studied mice with hepatocyte- or adipocyte-specific sterol regulatory-element binding protein-1c (SREBP-1c) overexpression as models of PRIM and SEC. PRIM mice featured increased lipogenic gene expression in liver and adipose tissue. Their selective, liver-specific insulin resistance was associated with increased C18:1-diacylglycerol (DAG) content and protein kinase C (PKC)ε translocation...
May 10, 2017: Diabetes
https://www.readbyqxmd.com/read/28490236/cinnamyl-alcohol-the-bioactive-component-of-chestnut-flower-absolute-inhibits-adipocyte-differentiation-in-3t3-l1-cells-by-downregulating-adipogenic-transcription-factors
#19
Dae Il Hwang, Kyung-Jong Won, Do-Yoon Kim, Bokyung Kim, Hwan Myung Lee
The extract of chestnut (Castanea crenata var. dulcis) flower (CCDF) has antioxidant and antimelanogenic properties, but its anti-obesity properties have not been previously examined. In this study, we tested the effect of CCDF absolute on adipocyte differentiation by using 3T3-L1 cells and determining the bioactive component of CCDF absolute in 3T3-L1 cell differentiation. CCDF absolute (0.1-100[Formula: see text][Formula: see text]g/mL) did not change 3T3-L1 cell viability. At 50[Formula: see text][Formula: see text]g/mL and 100[Formula: see text][Formula: see text]g/mL, the absolute significantly reduced the accumulation of lipid droplets in 3T3-L1 cells that were induced by culture in medium containing 3-isobutyl-1-methylxanthine/dexamethasone/insulin (MDI)...
May 11, 2017: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/28488421/retinoic-acid-modulates-lipid-accumulation-glucose-concentration-dependently-through-inverse-regulation-of-srebp-1-expression-in-3t3l1-adipocytes
#20
Mabrouk Attia Abd Eldaim, Shinya Matsuoka, Yuko Okamatsu-Ogura, Akihiro Kamikawa, Mohamed Mohamed Ahmed, Akira Terao, Kei-Ichi Nakajima, Kazuhiro Kimura
It is well known that retinoic acid (RA) suppresses adipogenesis, although there are some contradicting reports. In this study, we examined the effect of extracellular glucose on RA-induced suppression of adipogenesis in 3T3L1 cell culture. When the cells were cultured in normal glucose medium (NG), the addition of RA suppressed lipid accumulation. However, when cultured in high glucose medium (HG), addition of RA to the cells enhanced lipid accumulation. These changes were accompanied by parallel alterations in fatty acid synthase (FAS) and sterol regulatory element-binding protein (SREBP)-1 gene expression...
May 10, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
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