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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
Jamie N Connarn, Ruijuan Luo, Jim Windak, Xinyuan Zhang, Andrew Babiskin, Marisa Kelly, Gloria Harrington, Vicki L Ellingrod, Masoud Kamali, Melvin McInnis, Duxin Sun
Bupropion and its three active metabolites exhibit clinical efficacy in the treatment of major depression, seasonal depression, and smoking cessation. The pharmacokinetics of bupropion in humans is highly variable. It is unknown if there are any non-reported metabolites formed in humans in addition to the three known active metabolites. In this paper, we report newly identified and non-reported metabolites of bupropion in human plasma samples. Human subjects were dosed with a single oral dose of 75 mg of an immediate release bupropion HCl tablet...
October 10, 2016: Biopharmaceutics & Drug Disposition
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
Mohammed Kaplan, Cecilia Pinto, Klaartje Houben, Marc Baldus
Increasing evidence suggests that most proteins occur and function in complexes rather than as isolated entities when embedded in cellular membranes. Nuclear magnetic resonance (NMR) provides increasing possibilities to study structure, dynamics and assembly of such systems. In our review, we discuss recent methodological progress to study membrane-protein complexes (MPCs) by NMR, starting with expression, isotope-labeling and reconstitution protocols. We review approaches to deal with spectral complexity and limited spectral spectroscopic sensitivity that are usually encountered in NMR-based studies of MPCs...
January 2016: Quarterly Reviews of Biophysics
Hai Wang, Miaoyun Zhao, Neetu Sud, Patricia Christian, Jing Shen, Yongyan Song, Anjeza Pashaj, Kezhong Zhang, Timothy Carr, Qiaozhu Su
Insulin induced gene-2 (Insig-2) is an ER-resident protein that inhibits the activation of sterol regulatory element-binding proteins (SREBPs). However, cellular factors that regulate Insig-2 expression have not yet been identified. Here we reported that cyclic AMP-responsive element-binding protein H (CREBH) positively regulates mRNA and protein expression of a liver specific isoform of Insig-2, Insig-2a, which in turn hinders SREBP-1c activation and inhibits hepatic de novo lipogenesis. CREBH binds to the evolutionally conserved CRE-BP binding elements located in the enhancer region of Insig-2a and upregulates its mRNA and protein expression...
2016: Scientific Reports
Kathrin Gieseler, Hiroshi Qadota, Guy M Benian
In C. elegans, mutants that are defective in muscle function and/or structure are easy to detect and analyze since: 1) body wall muscle is essential for locomotion, and 2) muscle structure can be assessed by multiple methods including polarized light, electron microscopy (EM), Green Fluorescent Protein (GFP) tagged proteins, and immunofluorescence microscopy. The overall structure of the sarcomere, the fundamental unit of contraction, is conserved from C. elegans to man, and the molecules involved in sarcomere assembly, maintenance, and regulation of muscle contraction are also largely conserved...
August 23, 2016: WormBook: the Online Review of C. Elegans Biology
Miquel Moreno, Ricard Gelabert, José M Lluch
Recently synthesized BF2 -coordinated azo derivatives have been proposed as photoswitches that operate in the optical window (λ=600-1200 nm) for use in bioimaging applications. Herein, we have theoretically analyzed these compounds and modified some substituents to analyze which properties of the molecule govern its photochemistry. Our results compare rather well with the available experimental data, so our methodology, based on density functional theory (DFT) calculations for the ground electronic state and time-dependent-DFT for the first excited electronic state, is validated...
September 19, 2016: Chemphyschem: a European Journal of Chemical Physics and Physical Chemistry
Janey Sewell, Andrew Speakman, Andrew N Phillips, Valentina Cambiano, Fiona C Lampe, Richard Gilson, David Asboe, Nneka Nwokolo, Amanda Clarke, Ali Ogilvy, Simon Collins, Alison J Rodger
BACKGROUND: The annual number of new human immunodeficiency virus (HIV) infections among men who have sex with men (MSM) has risen in the United Kingdom and, of those who are HIV positive, the proportion undiagnosed is high. OBJECTIVE: The prospective AURAH2 study aims to assess factors associated with HIV acquisition among MSM in the United Kingdom and to investigate changes over time within individuals in sexual behavior and HIV-testing practices. METHODS: AURAH2 is a prospective study among MSM without diagnosed HIV, aiming to recruit up to 1000 sexually active MSM attending sexual health clinics in London and Brighton in the United Kingdom...
2016: JMIR Research Protocols
Janet B Meehl, Brian A Bayless, Thomas H Giddings, Chad G Pearson, Mark Winey
Basal bodies comprise nine symmetric triplet microtubules that anchor forces produced by the asymmetric beat pattern of motile cilia. The ciliopathy protein Poc1 stabilizes basal bodies through an unknown mechanism. In poc1∆ cells, electron tomography reveals subtle defects in the organization of intertriplet linkers (A-C linkers) that connect adjacent triplet microtubules. Complete triplet microtubules are lost preferentially near the posterior face of the basal body. Basal bodies that are missing triplets likely remain competent to assemble new basal bodies with nine triplet microtubules, suggesting that the mother basal body microtubule structure does not template the daughter...
August 1, 2016: Molecular Biology of the Cell
Sheida Torabi, Nancy M DiMarco
Assessing the effects of grapes and grape powder extracted polyphenols on lipogenesis and glucose uptake in adipocytes may clarify the risk/benefit of recommending them to individuals with obesity and insulin resistance. We investigated the effect of grape powder extracted polyphenols (GPEP) on intracellular fat accumulation and glucose uptake during differentiation of 3T3-F442A preadipocytes. Total polyphenols were extracted and measured based on gallic acid equivalents (GAE). There were 2167 mg of GAE polyphenols in 100 g of grape powder...
October 2016: Experimental Biology and Medicine
Yaoyao Jia, Chunyan Wu, Jiyoung Kim, Bobae Kim, Sung-Joon Lee
We have previously reported that astaxanthin (AX), a dietary carotenoid, directly interacts with peroxisome proliferator-activated receptors PPARα and PPARγ, activating PPARα while inhibiting PPARγ, and thus reduces lipid accumulation in hepatocytes in vitro. To investigate the effects of AX in vivo, high-fat diet (HFD)-fed C57BL/6J mice were orally administered AX (6 or 30mg/kg body weight) or vehicle for 8weeks. AX significantly reduced the levels of triglyceride both in plasma and in liver compared with the control HFD mice...
February 2016: Journal of Nutritional Biochemistry
Songtao Li, Yujie He, Song Lin, Liuyi Hao, Yaxin Ye, Lin Lv, Zongxiang Sun, Huiru Fan, Zhiping Shi, Jie Li, Rennan Feng, Lixin Na, Yanwen Wang, Ying Li, Changhao Sun
SCOPE: Individuals deficient in vitamin D are more likely to have higher circulating cholesterol levels and cardiovascular diseases. However, the underlying mechanisms are still unclear. METHODS AND RESULTS: A cross-sectional survey, animal study, and in vitro experiments were conducted to investigate the effect and mechanisms of vitamin D deficiency on endogenous cholesterol metabolism. We demonstrated that vitamin D deficiency was positively associated with an increase of total serum cholesterol and low-density lipoprotein cholesterol levels in northern Chinese individuals...
April 2016: Molecular Nutrition & Food Research
Yu-Feng Song, Zhi Luo, Li-Han Zhang, Christer Hogstrand, Ya-Xiong Pan
The present study was conducted to investigate the effect of Cu exposure on ER stress and Ca(2+) homeostasis, and explore the underlying mechanism of the ER stress and disturbed Ca(2+) homeostasis in the regulation of hepatic lipid metabolism in yellow catfish Pelteobagrus fulvidraco. To this end, three experiments were conducted. In experiment 1, P. fulvidraco were exposed to three waterborne Cu concentrations for 56 days. Waterborne Cu exposure evoked ER stress and SREBP-1c activation and resulted in dysregulation of hepatic lipid metabolism in liver of P...
February 2016: Chemosphere
Chunming Cheng, Peng Ru, Feng Geng, Junfeng Liu, Ji Young Yoo, Xiaoning Wu, Xiang Cheng, Vanessa Euthine, Peng Hu, Jeffrey Yunhua Guo, Etienne Lefai, Balveen Kaur, Axel Nohturfft, Jianjie Ma, Arnab Chakravarti, Deliang Guo
Tumorigenesis is associated with increased glucose consumption and lipogenesis, but how these pathways are interlinked is unclear. Here, we delineate a pathway in which EGFR signaling, by increasing glucose uptake, promotes N-glycosylation of sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP) and consequent activation of SREBP-1, an ER-bound transcription factor with central roles in lipid metabolism. Glycosylation stabilizes SCAP and reduces its association with Insig-1, allowing movement of SCAP/SREBP to the Golgi and consequent proteolytic activation of SREBP...
November 9, 2015: Cancer Cell
H L Cai, Q Y Tan, P Jiang, R L Dang, Y Xue, M M Tang, P Xu, Y Deng, H D Li, J K Yao
Previous findings suggested that a four-protein complex, including sterol-regulatory element-binding protein (SREBP), SREBP-cleavage-activating protein (SCAP), insulin-induced gene (INSIG) and progesterone receptor membrane component 1 (PGRMC1), within the endoplasmic reticulum appears to be an important regulator responsible for atypical antipsychotic drug (AAPD)-induced lipid disturbances. In the present study, effects of typical antipsychotic drug and AAPDs as well as treatment outcome of steroid antagonist mifepristone (MIF) on the PGRMC1/INSIG/SCAP/SREBP pathway were investigated in rat liver using real-time quantitative polymerase chain reaction (qPCR) and western blot analysis...
2015: Translational Psychiatry
Ayasa Ochiai, Shingo Miyata, Makoto Shimizu, Jun Inoue, Ryuichiro Sato
Elevated plasma low-density lipoprotein (LDL) cholesterol is considered as a risk factor for atherosclerosis. Because the hepatic LDL receptor (LDLR) uptakes plasma lipoproteins and lowers plasma LDL cholesterol, the activation of LDLR is a promising drug target for atherosclerosis. In the present study, we identified the naturally occurring alkaloid piperine, as an inducer of LDLR gene expression by screening the effectors of human LDLR promoter. The treatment of HepG2 cells with piperine increased LDLR expression at mRNA and protein levels and stimulated LDL uptake...
2015: PloS One
Daqian Xu, Zheng Wang, Yuxue Zhang, Wei Jiang, Yi Pan, Bao-Liang Song, Yan Chen
Cholesterol biosynthesis is regulated by transcription factors SREBPs and their escort protein Scap. On sterol depletion, Scap/SREBP complex is transported from endoplasmic reticulum (ER) to the Golgi apparatus where SREBP is activated. Under cholesterol sufficient condition, Insigs act as anchor proteins to retain Scap/SREBP in the ER. However, the anchor protein of Scap/SREBP in the Golgi is unknown. Here we report that a Golgi-localized membrane protein progestin and adipoQ receptors 3 (PAQR3) interacts with Scap and SREBP and tethers them to the Golgi...
2015: Nature Communications
Ruobing Ren, Xinhui Zhou, Yuan He, Meng Ke, Jianping Wu, Xiaohui Liu, Chuangye Yan, Yixuan Wu, Xin Gong, Xiaoguang Lei, S Frank Yan, Arun Radhakrishnan, Nieng Yan
Insulin-induced gene 1 (Insig-1) and Insig-2 are endoplasmic reticulum membrane-embedded sterol sensors that regulate the cellular accumulation of sterols. Despite their physiological importance, the structural information on Insigs remains limited. Here we report the high-resolution structures of MvINS, an Insig homolog from Mycobacterium vanbaalenii. MvINS exists as a homotrimer. Each protomer comprises six transmembrane segments (TMs), with TM3 and TM4 contributing to homotrimerization. The six TMs enclose a V-shaped cavity that can accommodate a diacylglycerol molecule...
July 10, 2015: Science
Xuedong Tong, Patricia Christian, Miaoyun Zhao, Hai Wang, Regis Moreau, Qiaozhu Su
The activation of sterol regulatory element binding proteins (SREBPs) is regulated by insulin-induced genes 1 and 2 (Insig-1 and Insig-2) and SCAP. We previously reported that feeding R-α-lipoic acid (LA) to Zucker diabetic fatty (ZDF) rats improves severe hypertriglyceridemia. In this study, we investigated the role of cyclic AMP-responsive element binding protein H (CREBH) in the lipid-lowering mechanism of LA and its involvement in the SREBP-1c and Insig pathway. Incubation of McA cells with LA (0.2 mM) or glucose (6 mM) stimulated activation of CREBH...
September 2015: Journal of Nutritional Biochemistry
Ruili Dang, Pei Jiang, Hualin Cai, Huande Li, Ren Guo, Yanqin Wu, Lihong Zhang, Wenye Zhu, Xin He, Yiping Liu, Ping Xu
Metabolic syndrome is a major concern in psychotic patients receiving atypical antipsychotics. Recent evidence suggests that sterol regulatory element-binding proteins (SREBPs) and insulin-induced genes (INSIGs) are implicated in the antipsychotic-induced metabolic side-effects. Vitamin D (VD) deficiency, a highly prevalent phenomenon among patients with psychosis, might also predispose individuals to metabolic syndrome Considering that VD has modulating effects on the INSIG/SREBP pathway, it is possible that VD may have a role in the antipsychotic-induced metabolic disturbances involving its effects on the INSIG/SREBP system...
August 2015: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
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