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Journal of Lipid Research

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https://www.readbyqxmd.com/read/27913585/the-influence-of-placental-metabolism-on-fatty-acid-transfer-to-the-fetus
#1
Simone Perazzolo, Birgit Hirschmugl, Christian Wadsack, Gernot Desoye, Rohan M Lewis, Bram G Sengers
The factors determining Fatty acid transfer across the placenta are not fully understood. This study used a combined experimental and computational modelling approach to explore placental transfer of non-esterified fatty acids and identify rate-determining processes. The isolated perfused human placenta was used to study the uptake and transfer of [(13)C]-fatty acids and the release of endogenous fatty acids. Only 6.2 ± 0.8% of the maternal (13)C-fatty acids taken up by the placenta was delivered to the fetal circulation...
December 2, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27913584/nitro-fatty-acid-pharmacokinetics-in-the-adipose-tissue-compartment
#2
Marco Fazzari, Nicholas K H Khoo, Steven R Woodcock, Diane K Jorkasky, Lihua Li, Francisco J Schopfer, Bruce A Freeman
Electrophilic nitro-fatty acids (NO2-FAs) promote adaptive and anti-inflammatory cell signaling responses as a result of an electrophilic character that supports post-translational protein modifications. A unique pharmacokinetic profile is expected for NO2-FAs because of an ability to undergo reversible reactions including Michael additions with biological cysteine-containing proteins and esterification into complex lipids. Herein we report via quantitative whole-body autoradiography analysis of rats gavaged with radiolabeled 10-nitro-[14C]oleic acid, preferential accumulation in adipose tissue over two weeks...
December 2, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27913583/epigenetic-control-of-microsomal-prostaglandin-e-synthase-1-by-hdac-mediated-recruitment-of-p300
#3
Christian Fork, Andrea E Vasconez, Patrick Janetzko, Carlo Angioni, Yannick Schreiber, Nerea Ferreiros, Gerd Geisslinger, Matthias S Leisegang, Dieter Steinhilber, Ralf P Brandes
: Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most widely used medicine to treat pain, fever, inflammation and to inhibit platelet function. Understanding the expression regulation of enzymes of the prostanoid pathway is of great medical relevance. Histone acetylation crucially controls gene expression. We set out to identify the impact of histone deacetylases (HDACs) on the generation of prostanoids and examine the consequences on vascular function. Inhibition of HDACs (HDACi) with the pan HDAC inhibitor SAHA attenuated prostaglandin E2 (PGE2) generation in the murine vasculature and in human vascular smooth muscle cells...
December 2, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27903595/lifelong-imbalanced-linoleic-alpha-linolenic-acid-intake-impairs-emotional-and-cognitive-behavior-in-adult-rats-via-changes-in-brain-endocannabinoid-system
#4
Erica Zamberletti, Fabiana Piscitelli, Valentina De Castro, Elisabetta Murru, Marina Gabaglio, Paola Colucci, Chiara Fanali, Pamela Prini, Tiziana Bisogno, Mauro Maccarrone, Patrizia Campolongo, Sebastiano Banni, Tiziana Rubino, Daniela Parolaro
Imbalanced dietary n-3 and n-6 PUFA content has been associated with a number of neurological conditions. Endocannabinoids are n-6 PUFA derivatives, whose brain concentrations are sensitive to modifications of fatty acid composition of the diet, and play a central role in the regulation of mood and cognition. As such, the endocannabinoid system appears to be an ideal candidate for mediating the effects of dietary fatty acids on mood and cognition. Lifelong administration of isocaloric alpha linolenic acid (ALA) deficient and enriched diets induced short-term memory deficits, whereas only dietary ALA enrichment altered emotional reactivity in adult male rats compared to animals fed a standard diet, balanced in ALA/linoleic (LA) ratio...
November 30, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27895090/identification-of-roles-for-h264-h306-h439-and-h635-in-acid-dependent-lipoprotein-release-by-the-ldl-receptor
#5
Hongyun Dong, Zhenze Zhao, Drake G LeBrun, Peter Michaely
Lipoproteins internalized by the LDL receptor are released from this receptor in endosomes through a process that involves acid-dependent conformational changes in the receptor ectodomain. How acidic pH promotes this release process is not well understood. Here, we assessed roles for six histidine residues for which either genetic or structural data suggested a possible role in the acid-responsiveness of the LDLR. Using assays that measured conformational change, acid-dependent lipoprotein release, LDLR recycling, and net lipoprotein uptake, we show that H635 plays important roles in acid-dependent conformational change and lipoprotein release, while H264, H306 and H439 play ancillary roles in the response of the LDLR to acidic pH...
November 28, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27895089/oxidized-high-density-lipoprotein-induces-macrophage-apoptosis-via-toll-like-receptor-4-dependent-chop-pathway
#6
Shutong Yao, Hua Tian, Li Zhao, Jinguo Li, Libo Yang, Feng Yue, Yanyan Li, Peng Jiao, Nana Yang, Yiwei Wang, Xiangjian Zhang, Shucun Qin
Oxidized high-density lipoprotein (ox-HDL), unlike native HDL that exerts antiatherogenic effects, plays a proatherogenic role. However, the underlying mechanisms are not completely understood. This study was designed to explore the inductive effect of ox-HDL on endoplasmic reticulum (ER) stress-C/EBP homologous protein (CHOP)-mediated macrophage apoptosis and its upstream mechanisms. Our results showed that ox-HDL could be ingested by macrophages, causing intracellular lipid accumulation. Like tunicamycin (an ER stress inducer), ox-HDL induced macrophage apoptosis with concomitant activation of ER stress pathway, including nuclear translocation of activating transcription factor 6, phosphorylation of protein kinase-like ER kinase and eukaryotic translation initiation factor 2α, and upregulation of glucose regulated protein 78 and CHOP, which were inhibited by 4-phenylbutyric acid (PBA, an ER stress inhibitor) and CHOP gene silencing...
November 28, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27884963/ectopic-fat-deposition-contributes-to-age-associated-pathology-in-caenorhabditis-elegans
#7
Konstantinos Palikaras, Meropi Mari, Barbara Petanidou, Angela Pasparaki, George Filippidis, Nektarios Tavernarakis
Age-dependent collapse of lipid homeostasis results in spillover of lipids and excessive fat deposition in non-adipose tissues. Ectopic fat contributes to lipotoxicity and has been implicated in the development of a metabolic syndrome that increases risk of age-associated diseases. However, the molecular mechanisms coupling ectopic fat accumulation with ageing remain obscure. Here, we use nonlinear imaging modalities to visualize and quantify age-dependent ectopic lipid accumulation in Caenorhabditis elegans...
November 24, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27884962/triheptanoin-long-term-effects-in-the-very-long-chain-acyl-coa-dehydrogenase-vlcad-deficient-mouse
#8
Sara Tucci, Ulrich Floegel, Frauke Beermann, Sidney Behringer, Ute Spiekerkoetter
A rather new approach in the treatment of long-chain fatty acid oxidation disorders is represented by triheptanoin, a triglyceride with three medium-odd-chain heptanoic acid (C7) due to its anaplerotic potential. We here investigate the effects of a one-year triheptanoin-based diet on the clinical phenotype of very long-chain-acyl-CoA-dehydrogenase-deficient (VLCAD-/-) mice. The cardiac function was assessed in VLCAD-/- mice by in vivo MRI. Metabolic adaptations were identified by the expression of genes regulating energy metabolism and anaplerotic processes using real-time-PCR and the results were correlated with the measurement of the glycolytic enzymes pyruvate dehydrogenase (PDH) and pyruvate kinase (PK)...
November 24, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27884961/therapeutic-silencing-of-fat-specific-protein-27-improves-glycemic-control-in-mouse-models-of-obesity-and-insulin-resistance
#9
Cédric Langhi, Noemí Arias, Ananthi Rajamoorthi, Jeannine Basta, Richard G Lee, Ángel Baldán
Obesity is a component of the metabolic syndrome, mechanistically linked to diabetes, fatty liver disease, and cardiovascular disease. Proteins that regulate the metabolic fate of intracellular lipid droplets are potential therapeutic candidates to treat obesity and its related consequences. CIDEC (cell death-inducing DFFA-like effector C), also known in mice as Fsp27 (fat-specific protein 27), is a lipid droplet-associated protein that prevents lipid mobilization and promotes intracellular lipid storage. The consequences of complete loss of FSP27 on hepatic metabolism and on insulin resistance are controversial, as both healthy and deleterious lipodystrophic phenotypes have been reported in Fsp27-/- mice...
November 24, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27881717/localization-of-1-deoxysphingolipids-to-mitochondria-induces-mitochondrial-dysfunction
#10
Irina Alecu, Andrea Tedeschi, Natascha Behler, Klaus Wunderling, Christian Lamberz, Mario A R Lauterbach, Anne Gaebler, Daniela Ernst, Paul P Van Veldhoven, Ashraf Al-Amoudi, Eicke Latz, Alaa Othman, Lars Kuerschner, Thorsten Hornemann, Frank Bradke, Christoph Thiele, Anke Penno
1-Deoxysphingolipids (deoxySLs) are atypical sphingolipids that are elevated in the plasma of patients with type 2 diabetes and hereditary sensory and autonomic neuropathy type 1 (HSAN1). Clinically, diabetic neuropathy and HSAN1 are very similar, suggesting the involvement of deoxySLs in the pathology of both diseases. However, very little is known about the biology of these lipids and the underlying pathomechanism. We synthesized an alkyne analogue of 1-deoxysphinganine (doxSA), the metabolic precursor of all deoxySLs, to trace the metabolism and localization of deoxySLs...
November 23, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27881716/influence-of-route-of-administration-and-lipidation-of-apolipoprotein-a-i-peptide-on-pharmacokinetics-and-cholesterol-mobilization
#11
Jie Tang, Dan Li, Lindsey Drake, Wenmin Yuan, Sarah Deshaine, Emily E Morin, Rose Ackermann, Karl Olsen, David E Smith, Anna Schwendeman
Apoliprotein A-I (apoA-I), apoA-I mimetic peptides and their lipid complexes or reconstituted high-density lipoprotein (HDL) have been studied as treatments for various pathologies. However, consensus is lacking about the best method for administration - by intravenous (IV) or intra-peritoneal (IP) routes, and formulation - as an HDL particle or in a lipid-free form. The objective of this study was to systematically examine peptide plasma levels, cholesterol mobilization and lipoprotein remodeling in vivo following administration of lipid-free apoA-I peptide (22A) or phospholipid reconstituted 22A-sHDL by IV and IP routes...
November 23, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27881715/s1p-in-hdl-promotes-interaction-between-sr-bi-and-s1pr1-and-activates-s1pr1-mediated-biological-functions-calcium-flux-and-s1pr1-internalization
#12
Mi-Hye Lee, Kathryn M Appleton, Hesham M El-Shewy, Mary G Sorci-Thomas, Michael J Thomas, Maria F Lopes-Virella, Louis M Luttrell, Samar M Hammad, Richard L Klein
HDL normally transports about 50-70% of plasma S1P and the S1P in HDL reportedly mediates several HDL-associated biological effects and signaling pathways. The HDL receptor, SR-BI, as well as the cell surface receptors for S1P (S1PRs) may be involved partially and/or completely in these HDL-induced processes. Here we investigate the nature of the HDL-stimulated interaction between the HDL receptor, SR-BI, and S1PR1 using a protein-fragment complementation assay (PCA) and confocal microscopy. In both primary rat aortic vascular smooth muscle (RVSMC) and HEK293 cells, the S1P content in HDL particles increased intracellular calcium concentration that was mediated by S1PR1...
November 23, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27879312/association-of-peripheral-differential-leukocyte-counts-with-dyslipidemia-risk-in-chinese-patients-with-hypertension-insight-from-the-csppt
#13
Yanhong Liu, Xiangyi Kong, Wen Wang, Fangfang Fan, Yan Zhang, Min Zhao, Yi Wang, Yupeng Wang, Yu Wang, Xianhui Qin, Genfu Tang, Binyan Wang, Xiping Xu, Fan Fan Hou, Wei Gao, Ningling Sun, Jianping Li, Scott A Venners, Shanqun Jiang, Yong Huo
The aim of the present study was to examine the association between peripheral differential leukocyte counts and dyslipidemia in a Chinese hypertensive population. A total of 10866 patients with hypertension were enrolled for a comprehensive assessment of cardiovascular risk factors using data from the China Stroke Primary Prevention Trial (CSPPT). Plasma lipid levels and total leukocyte, neutrophil and lymphocyte counts were determined according to standard methods. Peripheral differential leukocyte counts were consistently and positively associated with serum TC, LDL-C and TG levels (all P<0...
November 22, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27872144/cytotoxic-1-deoxysphingolipids-are-metabolized-by-a-cytochrome-p450-dependent-pathway
#14
Irina Alecu, Alaa Othman, Anke Penno, Essa M Saied, Christoph Arenz, Arnold von Eckardstein, Thorsten Hornemann
1-Deoxysphingolipids (1-deoxySLs) are atypical sphingolipids which are formed when serine palmitoyltransferase condenses palmitoyl-CoA with alanine instead of serine during sphingolipid synthesis. 1-DeoxySLs are toxic to neurons and pancreatic beta-cells. Pathologically elevated 1-deoxySLs cause the inherited neuropathy HSAN1 and are also found in type 2 diabetes. Diabetic sensory polyneuropathy and HSAN1 are clinically very similar, suggesting that 1-deoxySLs may be implicated in both pathologies. 1-DeoxySLs are considered to be dead-end metabolites, as they lack the C1-hydroxyl group which is essential for the canonical degradation of sphingolipids...
November 21, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27864326/both-maternal-and-offspring-elovl2-genotypes-determine-systemic-dha-levels-in-perinatal-mice
#15
Anna M Pauter, Sofia Trattner, Amanda Gonzalez-Bengtsson, Emanuela Talamonti, Abolfazl Asadi, Olga Dethlefsen, Anders Jacobsson
The molecular details relevant to dietary supplementation of the omega-3 fatty acid docosahexaenoic acid (DHA) in mothers as well as in their offspring are not clear. The polyunsaturated fatty acid (PUFA) elongase Elongation of very long-chain 2 (ELOVL2) is a critical enzyme in the formation of DHA in mammals. In order to address the question regarding the origin of DHA during perinatal life we have used DHA deficient Elovl2-ablated mice as a model system to analyse the maternal impact on the DHA level in their offspring of various genotypes...
November 18, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27856675/metabolism-and-phospholipid-assembly-of-polyunsaturated-fatty-acids-in-human-bone-marrow-mesenchymal-stromal-cells
#16
Feven Tigistu-Sahle, Milla Lampinen, Lotta Kilpinen, Minna Holopainen, Petri Lehenkari, Saara Laitinen, Reijo Käkelä
High arachidonic acid (20:4n-6) and low n-3 polyunsaturated fatty acid (PUFA) levels impair the capacity of cultured human bone marrow mesenchymal stromal cells (hBMSCs) to modulate immune functions. Capacity of the hBMSCs to modify PUFA structures was found to be limited. Therefore different PUFA supplements given to the cells resulted in very different glycerophospholipid (GPL) species profiles and substrate availability for phospholipases, which have preferences for polar head group and acyl chains when liberating PUFA precursors for production of lipid mediators...
November 16, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27875259/monoclonal-antibodies-that-bind-to-the-ly6-domain-of-gpihbp1-abolish-the-binding-of-lpl
#17
Xuchen Hu, Mark W Sleeman, Kazuya Miyashita, MacRae F Linton, Christopher M Allan, Cuiwen He, Mikael Larsson, Yiping Tu, Norma P Sandoval, Rachel S Jung, Alaleh Mapar, Tetsuo Machida, Masami Murakami, Katsuyuki Nakajima, Michael Ploug, Loren G Fong, Stephen G Young, Anne P Beigneux
GPIHBP1, an endothelial cell protein, binds lipoprotein lipase (LPL) in the interstitial spaces and shuttles it to its site of action inside blood vessels. For years, studies of human GPIHBP1 have been hampered by an absence of useful antibodies. We reasoned that monoclonal antibodies (mAbs) against human GPIHBP1 would be useful for: (1) defining the functional relevance of GPIHBP1's Ly6 and acidic domains to the binding of LPL; (2) ascertaining whether human GPIHBP1 is expressed exclusively in capillary endothelial cells; and (3) testing whether GPIHBP1 is detectable in human plasma...
November 15, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27875257/nicotinic-acid-timed-to-feeding-reverses-tissue-lipid-accumulation-and-improves-glucose-control-in-obese-zucker-rats
#18
Tobias Kroon, Tania Baccega, Arne Olsén, Johan Gabrielsson, Nicholas D Oakes
Nicotinic acid (NiAc) is a potent inhibitor of lipolysis, acutely reducing plasma free fatty acid (FFA) concentrations. However, a major FFA rebound is seen during rapid NiAc washout and sustained exposure is associated with tolerance development, with FFA returning to pretreatment levels. Our aim was to find a rational NiAc dosing regimen which preserves FFA lowering, sufficient to reverse non-adipose tissue lipid accumulation and improve metabolic control, in obese Zucker rats. We compared feeding-period vs...
November 15, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27845688/differentiating-brown-and-white-adipose-tissues-by-high-resolution-diffusion-nmr-spectroscopy
#19
Sanjay Kumar Verma, Kaz Nagashima, Jadegoud Yaligar, Navin Michael, Swee Shean Lee, Tian Xianfeng, Venkatesh Gopalan, Suresh Anand Sadananthan, Rengaraj Ananthraj, S Sendhil Velan
There are two types of fat tissues, white adipose tissue (WAT) and brown adipose tissue (BAT), which essentially perform opposite functions in whole body energy metabolism. There is a large interest in identifying novel biophysical properties of WAT and BAT by a quantitative and easy-to-run technique. In this work, we used high-resolution pulsed field gradient diffusion NMR spectroscopy to study the apparent diffusion coefficient (ADC) of fat molecules in rat BAT and WAT samples. The ADC of fat in BAT and WAT from rats fed with a chow diet was compared to that of rats fed with a high-fat diet to monitor how the diffusion properties change due to obesity-associated parameters such as lipid droplet size, fatty acid chain length and saturation...
November 14, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27845687/extracellular-matrix-remodeling-and-transforming-growth-factor-%C3%AE-signaling-abnormalities-induced-by-lamin-a-c-variants-that-cause-lipodystrophy
#20
Caroline Le Dour, Wei Wu, Véronique Béréziat, Jacqueline Capeau, Corinne Vigouroux, Howard J Worman
Mutations in the lamin A/C gene encoding nuclear lamins A and C (lamin A/C) cause familial partial lipodystrophy type 2 (FPLD2) and related lipodystrophy syndromes. These are mainly characterized by redistribution of adipose tissue associated with insulin resistance. Several reports suggest that alterations in the extracellular matrix of adipose tissue leading to fibrosis play a role in the pathophysiology of lipodystrophy syndromes. However, the extent of extracellular matrix alterations in FPLD2 remains unknown...
November 14, 2016: Journal of Lipid Research
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