Day 3 :
Keynote Forum
Ho Nam Chang
KAIST, Korea
Keynote: Techno-economic assessment of microbial lipids based on volatile fatty acids substrate by oleaginous Cryptococcus curvature
Time : 09:30-10:00
Biography:
Ho Nam Chang has completed his PhD from Stanford University in Chemical Engineering (1971). After one year’s postdoctoral studies from Iowa State Univ., he returned to KAIST, Korea in 1976, where he served for 39 years until his retirement in February 2015 (as Professor Emeritus). He has been continuing his work on microbial biodiesel and osmotic pressure using reverse osmosis in Pukyung National and Chungbuk National Universities for successful commercialization of microbial biodiesel from low cost biomass such as food waste. He has published more than 365 papers in reputed journals, 10,290 citations (h-index 56, Google scholar) and has been serving as Advisory Board Member of Biotechnology and Bioengineering, the best journal in Biotechnology (Engineering) area by Wiley-Blackwell.
Abstract:
Techno-economic microbial diesel production were assessed using commercial simulation software (SuperProDesigner, Intelligen.com) in terms of raw material cost, microbial lipid yield over substrate (g/g), lipid content of cells, bioreactor productivity and cost of downstream processing. The simulation shows that glucose is not suitable because of its high cost. Volatile fatty acids (VFAs) derived from low cost biomass were found to be the most suitable substrate since VFAs can be produced at lowest processing cost even from lignocellulosic biomass. For bioreactor productivity multi-stage continuous high cell density culture (MSC-HCDC) was employed, which gives high bioreactor productivity together with product titer. Current experimental product titer of 5 wt% needs to remove about 550 g water from the fermentation broth. Thermal methods require high energy consumption for simple evaporation, in terms of kwh/m3 water removal, 706 and 25 while only 4 or less is needed if osmotic pressure free (Δπ=0) reverse osmosis is used. Also experimental of biolipid production kinetics of oleaginous C. curvature will be presented. At a VFAs cost of 150$/ton (biomass cost, 75$/ton, 50% yield) microbial diesel cost is estimated to be around 1.15$/L and 0$/ton VFAs gives a much lower cost. Further improvement of cells for higher VFAs yield from biomass and microbial lipid yield, and overproduction and secretion of lipids may cut down the cost further.
- Lipidomics- whats next?, Fats - Cardio metabolic risks, Lipids in Signalling and Intra Cellular Trafficking
Location: Sausalito
Chair
Srdjan Djurovic
Oslo University Hospital, Norway
Co-Chair
Kuo-Liong Chien
National Taiwan University, Taiwan
Session Introduction
Srdjan Djurovic
Oslo University Hospital, Norway
Title: Improved detection of common variants associated with schizophrenia by leveraging pleiotropy with cardiovascular disease risk factors/lipids
Time : 12:15-12:40
Biography:
Srdjan Djurovic obtained his Dr. Sci. Med. (PhD) from University of Zagreb, Croatia and University of Graz, Austria. He is a Group leader/Professor at the Department of Medical Genetics, and NORMENT Center of Excellence, University of Bergen and Oslo University Hospital – Ullevål, Oslo, Norway, He has published more than 170 papers in reputed journals and has been serving as a reviewer and Guest Professor of repute.
Abstract:
Several lines of evidence suggest that genome-wide association studies (GWAS) have the potential to explain more of the ‘missing heritability’ of common complex phenotypes. However, reliable methods to identify a larger proportion of single nucleotide polymorphisms (SNPs) are currently lacking. Here, we present a genetic pleiotropy-informed method to improve gene discovery using GWAS summary statistics data. We apply this methodology to identify new loci associated with schizophrenia (SCZ), a highly heritable disorder with significant missing heritability. Epidemiological and clinical studies suggest co-morbidity between SCZ and cardiovascular disease (CVD) risk factors, including systolic blood pressure, triglycerides, low and high-density lipoprotein, body mass index, waist-hip-ratio, immunological parameters, and type 2 diabetes. We validate this ‘pleiotropic enrichment’ by demonstrating increased replication rate across independent SCZ sub-studies. We have recently replicated these findings in larger sample. The majority of the loci are associated with both SCZ and CVD risk factors, mainly triglycerides, low and high-density lipoproteins. Together, these findings suggest the feasibility of using genetic pleiotropy-informed methods to improve gene discovery in SCZ and identify potential mechanistic relationships with various CVD risk factors. The larger part of the pleiotropic signal was found with lipid levels, suggesting that lipid biology may be involved in schizophrenia pathophysiology. As such, genetically determined dyslipidemia in schizophrenia is in line with evidence for white matter abnormalities and myelin dysfunction and supports the neurodevelopmental hypothesis of schizophrenia.
Ahmed Ibrahim
Cairo University School of Medicine,Egypt Cleveland Clinic Foundation, Cleveland,USA
Title: Lipid profile in Egyptian patients with coronary artery disease, role of age, gender and hypertension
Time : 12:40-13:05
Biography:
Ahmed Ibrahim has completed his Cardiology fellowship at Cairo University hospital with a Masters’ Thesis that which provided new insight on CAD in Egyptian Women. He worked as a research associate in Cardiology at Loyola in Chicago then in University California San Diego then did general medicine residency in Case Western/ St Vincent hospital in Cleveland. For the last three years, he has been working as an associate staff in the heart and vascular institute in Cleveland Clinic.
Abstract:
Background No data are available about plasma lipid profile in Egyptians with coronary artery disease (CAD). Plasma lipid profile may differ according to ethnic origin and geographic area. Objectives Identify plasma lipid abnormalities in Egyptians with CAD and define the role of age, type of CAD, and the presence of hypertension (HT) on lipid profile. Methods Retrospective consecutive sampling of lipid profile of 1000 patients with CAD. Results were compared to a control group of 1920 non-coronary individuals. Results Patients’ age range was 19–90 years. HT was present in 56.7% of patients. The commonest isolated lipid abnormality was a reduced HDL-C in men and increased plasma triglycerides (TG) in women. Patients with myocardial infarction (MI) had a lower HDL-C than those with angina pectoris (AP). Abnormalities were more severe and more prevalent in the young age group. No significant difference in lipid profile was present between normotensive (NT) and hypertensive (HT) CAD patients. Conclusion Dyslipidemia is common among Egyptians with CAD. Lipid profile was influenced by age, gender, type of CAD, but not by the presence of HT. The high prevalence rate of risk factors particularly among young Egyptians is remarkable and can explain the epidemic of CAD among Egyptians.
Kuo-Liong Chien
National Taiwan University, Taiwan
Title: Fatty acids as novel biomarkers for cardiovascular health
Time : 14:05-14:30
Biography:
Kuo-Liong Chien has been trained as a cardiologist and he received the PhD degree in Institute of Epidemiology, College of Public Health, National Taiwan University, majored in genetic epidemiology and cardiovascular epidemiology. Now as the Professor and Director in the Institute of Epidemiology and Preventive Medicine, NTU, he has conducted a prospective cohort study in a community, focused on cardiovascular disease risk factor prevention. In addition, he applied epidemiological and statistical methods in resolving important cardiovascular disease problems. He has published over 200 scientific papers in English on preventive cardiology, and his contribution to public health is on non-communicable disease (NCD) management and prevention in Taiwan.
Abstract:
A wide range of fatty acids, including saturated fatty acids, trans fats and n-3 fatty acids, have been linked to the risk of cardiovascular disease. However, the relationship between various fatty acids and the risk cardiovascular disease varied much according to different types of fatty acids. Even more, even specific saturated fats, including even, odd and long-chain, have been shown various effects. Our previous studies have shown the plasma n-3 fatty acids have a good correlation with dietary survey from a semi-quantitative food frequency questionnaire. In addition, we demonstrated the association between plasma fatty acid profiles and the status of metabolic syndrome among participants who received health checkup. Moreover, our cohort study clearly showed fatty acids were important predictors for the development of cardiovascular events and all-cause deaths among the participants in on community. We found that a mutually adjusted two-marker model indicated that saturated fats and trans fats were significant predictors of all-cause death and cardiovascular events and the trans fats presented the greatest improvement in net reclassification for all-cause death and saturated fats presented the greatest improvement in net reclassification for events. Recently, we are studying the specific roles of even, odd, and long-chain saturated fatty acids and delta-5 and delta-6 desaturases, the crucial enzymes in polyunsaturated fatty acid-related pathways, for the risk of cardiovascular events. We believe the contributions our serial studies are important for understanding the role of various fatty acids for the risk of cardiovascular health
Carla Ferreri
Consiglio Nazionale delle Ricerche, Italy
Title: Membrane lipidomics for personalized health
Time : 11:50-12:15
Biography:
Carla Ferreri holds the position of Senior Researcher at ISOF-CNR, Bologna (Italy). Her present research interests are in the field of free radical chemistry, biomimetic chemistry of stress conditions affecting the main biological molecules (lipids, DNA, proteins), membrane lipidomics, biomarker and novel nanotechnology development with application in life sciences, nutrition and molecular medicine. She is responsible of the CNR research project on lipidomics and nutraceuticals, co-founder of two spin-off companies in Italy and Greece, consultant for AZTI, a Spanish company on nutra-innovation, and author of more than 150 papers, 2 books and 3 patents
Abstract:
Each organism and biological compartment has its own lipid composition, defined as the lipidome, which can be monitored by lipidomics. In particular, lipidomics revealed the precious information embedded in the correct assembly of phospholipids, to provide organization and functionality of the complex and homeostatic system of cell membranes at best. Membrane lipidomics is influenced by various metabolic and environmental conditions and the extreme flexibility of membrane composition for cell and tissue functioning is also the novel aspect that attracted a lot of research and medical interest. Our work translated this knowledge into a practical tool for personalized medicine, based on profiles determined from the mature red blood cell membranes. An innovative robotics was designed for high-throughput application of the analysis to the build-up of a human database, in order to understand how inadequate diets and life styles can perturb membrane lipidome and be connected with further disease onset. Lipidomic profiling evidences fatty acids changes and unbalances associated with diseases, such as dermatology, celiac disease and autism. It also evidences that membranes can be “repaired” from incorrect profiles by appropriate and personalized nutra-strategies, using the natural cell turnover and membrane remodeling processes. Nutrilipidomics proposes the joint venture from membranes and nutrition, used in health prevention and diseases, and in the latter case, coordinated with the therapeutic intervention. The effects of recovering the functional homeostasis in favor of better health and quality of life are nowadays a result of evidence-based medicine ready to be brought to a wide clinical use
Malin L Nording
Umeå University, Sweden
Title: The journey towards improved bioactive lipid analysis
Time : 14:30-14:55
Biography:
Malin L Nording has completed her PhD from Umeå University, Sweden, and Post-doctoral studies from University of California, Davis. She has almost a decade of experience in metabolmics studies, with particular emphasis on the bioactive lipidome, including oxylipins such as eicosanoids and other fatty acid metabolites. She has been awarded an International Career Grant for her work on bioactive lipids, in collaboration with the Swedish Metabolomics Centre and the NIH West Coast Metabolomics Center
Abstract:
Profiling the oxylipin and endocannabinoid lipidome requires highly senstive, precise and robust methods, which can be accomodated by the use of liquid chromatography (LC) combined with tandem mass spectrometry (MS/MS) methods. We have developed several LC-MS/MS protocols for these bioactive lipids from different fatty acid precursors, mainly arachidonic and linoleic acid, but also from eicosapentaenoic and docosahexaenoic acid, as well as from other fatty acids. Orginally, we employed separate extraction protocols for each family of bioactive lipid (oxylipins and endocannabinoids, respectively), and also different LC-MS/MS equipments. But for application in clinical studies, it is more convenient to combine the analytical procedures for oxylipins and endocannabinoids in order to cover a larger portion of the lipidome in one single LC-MS/MS injection and preceeding sample extraction. It would allow for smaller sample volumes and less labour intensive work procedures. However, combined analysis of oxylipins and endocannabinoids is a challenging task, partly due to the different modes used for optimal ionization, negative for oxylipins and positive for endocannabinoids. Furthermore, the extraction solvents, mobile phases etc are not identical, so modifications of the previous (separate) protocols were necessary. I will describe our work towards combined analysis of oxylipins and endocannabinoids, which we currently have in place at the Swedish Metabolomics Centre in Umeå. Cruicial steps in the workflow will be highlighted and examples of succesful applications will be given
Akio Nakamura
Gunma University, Japan
Title: Eicosapentaenoic acid has improved the impaired insulin-signaling pathway of the cardiac muscle of infants
Time : 14:55-15:20
Biography:
Akio Nakamura, PhD is an Associate Professor in the Department of Molecular Pharmacology and Oncology at School of Medicine, Gunma University. He has published more than 50 papers in reputed journals
Abstract:
Previous many studies suggest that early nutrition during critical developmental periods affects long-term health. Infants of diabetic mothers (IDM) have also abnormal circulatory organs. When we investigated the insulin signaling in the newborn rat heart, they found that the insulin signaling showed insulin resistance at the Akt/mTOR pathway. However, we have already reported that the abnormality of insulin signaling of the infant hearts of diabetic mothers was improved by feeding the pregnant mothers a diet rich in fish oil. In this study, we would like to clarify that eicosapentaenoic acid (EPA) of ingredient of the fish-oil improves insulin signaling by diabetic mother’s infant’s hearts and the primary cardiomyocyte cells. Pregnant diabetic rats induced by streptozotocin and were then fed the EPA or DDW via gastric tube. To examine changes in insulin signaling in the cardiac muscle in IDM, we isolated the heart and cultured the primary cardiomyocyte cells. Western blotting was carried out for determine the Akt-related insulin signaling. The phosphorylation level of Akt and the expression level of mTOR and the GLUT4 translocation to the plasma membrane with insulin were decreased in IDM of the control group. However, the phosphorylation level of Akt, FOXO, Stat3 and the expression level of mTOR were increased compared with control group by EPA ingestion of mother. During pregnancy, the placenta transfers the EPA from the mother to the fetus. The EPA in the fish oil may improve the impaired signaling pathway of the cardiac muscle of infants caused by a diabetic mother's hyperglycemia
Ikuo Yokoyama
International University of Health and Welfare, Japan
Title: Ezetimibe - a new insight for anti-hyperlipidemic therapy. Lessons from a case Report Ezetimibe completely replaced LDL-apheresis for the treatment of familial hypercholesterolemia and coronary artery disease after CABG
Time : 15:20-15:45
Biography:
Ikuo Yokoyama graduated from Tohoku University School of Medicine and received MD and has completed his PhD from Graduate School of Medicine and Faculty of Medicine, The University of Tokyo and became Asistant Professor of Cardiovascular Medicine of the same institution at the age of 40 years and then became a Lecturer. He is permanent Research Fellow of the National Cardiovascular Research Center Research Institute and Associate Professor of International University of Health and Welfare. He has published 52 original papers in reputed journals
Abstract:
The effectiveness of anti-hyperlidemia therapy for preventing cardiovascular events and inducing regression of coronary artery stenosis has been demonstrated. Multicenter trials have indicated that hydroxymethylglutaryl coenzyme A reductase inhibitors (so-called statins) aid in preventing coronary artery disease (CAD). Furthermore, one statin has been reported to be more effective in reducing the occurence of cardiovascular events than percutaneous transluminal coronary revascularisation therapy. However, despite the fact that statins are currently the mainstay of dyslipidemia care, their efficacy in preventing a cardiovascular event still has limitations. This is because the ability of the statin to inhibit cholesterol production might exert adverse effects by restoring cholesterol levels via activation of reuptake of cholesterol derived from the small intestine. Ezetimibe has recently emerged as a new class of lipid-lowering medication, which acts via the inhibition of Niemann-Pick C1 Like 1, a protein localized in jejunal enterocytes. Combination therapy with ezetimibe and statins has been shown to be highly effective in the treatment of hypercholesterolemia. However, to date it has not been established whether ezetimibe combined with statin therapy has a much stronger effect than that of low density lipoprotein bound cholesterol (LDL)-apheresis, which is recognized as the most effective therapy for hyperlipidemia. I experienced a rare case in which ezetimibe appeared to play a central role, in place of LDL-apheresis, in a patient with familial hypercholesterolemia and CAD who had undergone coronary artery bypass grafting. This case is discussed here to increase our knowledge of ezetimibe and lipid care.
Yajnavalka Banerjee
SQ University, Oman
Title: Novel revelations in familial hypercholesterolemia and physiological anticoagulant lipids
Time : 15:45-16:05
Biography:
Dr. Yajnavalka Banerjee obtained his PhD from the National University of Singapore (NUS) and received his postdoctoral training at the reputed The Scripps Research Institute, La Jolla USA and Max-Planck Institute for Biophysical Chemistry Gottingen, Germany. He is currently, Associate Professor of Biochemistry in the College of Medicine and Health Sciences, SQU in Oman. He has published more than 40 papers in reputed internationally refereed journals and, is on the editorial board six journals. Dr. Banerjee also has two patents related to anticoagulant peptides
Abstract:
Lipids play pivotal role in the preservation of homeostasis in the physiological milieu. However, certain diseased states detrimentally affect the metabolism of lipids in turn disconcerting the fulcrum of homeostasis. Case in point, heterozygous familial hypercholesterolaemia (HeFH) a genetic disorder associated with considerable morbidity and mortality. The most common defect is loss-of-function (LOF) mutations in the low-density lipoprotein (LDL) receptor alleles (over 1600 mutations having been reported). Other more infrequent causes of FH are defects in apolipoprotein B (ApoB), (the protein in the LDL particle that binds to the LDL receptor) and gain-of-function (GOF) mutations in the pro-protein convertase subtilisin/kexin type 9 (PCSK9). In the first part of the disquisition, we appraise the effect of two new mutations on different protein-structural levels, identified in the LDL-receptor and PCSK9 genes in two Omani Arab families diagnosed with FH, according to Simon-Broome criteria, employing in silico tools. We also assess the mode of inheritance of these two mutations. The fact that lipids also exhibit cardio-protective activity is not a very well-investigate niche. The second part of the discourse is dedicated to the recently discovered anticoagulant effect of acylcarnitines. Our studies show that acylcarnitines inhibit factor Xa-initiated clotting. Inhibition of factor Xa by acylcarnitines is greater for longer acyl chain lengths. Mechanistic studies show that 16:0 acylcarnitine has anticoagulant activity in the absence of factor Va or phospholipids. Surface plasmon resonance investigations revealed that 16:0 acylcarnitine binds to factor Xa, and that binding is independent of the γ-carboxy glutamic acid domain
- Obesity and Health, Plant, Microbial lipids and Essential Oils, Lipids and Bioenergy and Protein-Lipid and Lipid-Lipid Interactions
Chair
Ho Nam Chang
KAIST, Korea
Co-Chair
Emmanuel Mukwevho
North West University, South Africa
Session Introduction
Peña Betancourt S.D.
Autonomous Metropolitan University. Campus Xochimilco, Mexico
Title: Comparision of the lipid content and the fumonisins concentration in maize genetic diversity
Time : 10:00-10:25
Biography:
Peña Betancourt S D is a Master in Science from the National Autonomous University of Mexico, clinical toxicology specialist and PhD from the University of Lyon, France. She is a full time Professor in the Agricultural and Animal Production Department at University Autonomous Metropolitan, campus Xochimilco and Head of the Laboratory of Toxicology. She has published 15 articles in national and international journals. She served as head of the research on quality safety of agricultural products Animal and Agricultural Production Department. She is a Tutor of the Master's and Doctoral programs in divers Institutions of higher education like UNAM, UAM, UAEM and UAZ.
Abstract:
In Mexico, corn is the staple food grain; per capita consumption is estimated at 800 g per day and that 70% of the population suffer from obesity and diabetes type 2. The aim of this study was to determine lipid content and fumonisin in maize genetic diversity, to avoid a potential health risk for high intake of carbohydrates and toxic substances that interfere with lipid metabolism. 25 samples were collected in three states (State of Mexico, Hidalgo and Morelos) at Central Regions in Mexico, (8) landraces were identified, (10) improved corn hybrids and (7) Bt corn, which were subjected to a lipid extraction method Golfisch, AOAC and total fumonisin by ELISA method (Ridascreen Fast Fumonisin). Chemical analysis confirmed a significant increase in total lipid content (8.075%) in Bt with respect to the non-Bt maize hybrids (5.07%). The presence of fumonisin levels was detected in 4 mg kg native and improved corn and 0.56 mg kg in Bt maize. In conclusion, the data showed an increase in total lipids in maize, which expressed a recombinant protein (Cry1Ab) and decreased levels fumonisin, regarding native and improved maize. Fumonisin levels detected may be a risk to consumer health. It is recommended to evaluate the additive effect of excess lipids and fumonisin in the diet of the Mexican population.
Emmanuel Mukwevho
North West University, South Africa
Title: Exercise-induced Calmodulin dependent protein kinase (CaMK)II activation regulates saturated and unsaturated fatty acids in rat skeletal muscle
Time : 10:25-10:50
Biography:
Emmanuel Mukwevho has completed his PhD in 2010 from University of Cape Town, South Africa in Anatomy and Cell Biology. He is an Associate Professor of Biochemistry at North West University, South Africa. He has published both nationally and internationally in reputed journals and his specialiality is in Obesity and Diabetes, where he lead the Diabetes & Obesity Therapeutics Research group at North West University
Abstract:
CaMKII regulates many pathways involved in the regulation of various cellular and molecular mechanisms that result in myriad health benefits. Exercise is a key activator of CaMKII, and shown to improve many functional activities in individuals who exercise compared with those who do not exercise, however the mechanism involved not yet fully elucidated, which became the objective of this study. In this study using rats, we investigated various lipids metabolism for both saturated and non-saturated fatty acids in rats that exercised, non-exercised and exercised+KN93 (CaMKII inhibitor). Lipids were analysed using GC×GC TOFMS. Palmitoleic acid and oleic acid which are monounsaturated fatty acids known to promote insulin sensitivity and improve glycaemic control were investigated. Levels of the exercise group showed ~2.0 fold increase compared with the non-exercise (control) group. Abolishing CaMKII activity by administration of KN93 significantly decreased exercise-induced Palmitoleic acid levels. Oleic acid levels of the exercise group were ~ 4.1 folds higher than the non-exercise group and followed the same pattern as Palmitoleic acid. Lauric acid is a saturated fatty acid, which increases fatty acid needed for better health. The exercise group showed ~ 8.7 fold increase compared with the non-exercise group of Lauric acid. The exercise + KN93 group significantly reduced induction by ~2.5 fold compared with the exercise group. On the other hand, Myristic acid and palmitic acid which are saturated fatty acids known to increase risk factors of metabolic syndrome. The myristic acid level of the exercise group decreased by ~3.4 fold compared with the control group, whereas the exercise + KN93 group significantly increased by ~4.3 compared with the exercise group. In conclusion, CaMKII can reduce the risk factors of metabolic syndrome and type 2 diabetes
Allison W Xu
University of California, San Francisco
Title: Regulation of hypothalamic neuronal function in obesity
Time : 11:10-11:35
Biography:
Allison W Xu completed her PhD at University of Texas - M.D. Anderson Cancer Center and conducted her Postdoctoral studies at Stanford University School of Medicine. Subsequently, she started her independent research program, and she is currently an Associate Professor in the Diabetes Center at University of California, San Francisco. Her laboratory focuses on understanding how hypothalamic neurons sense and respond to peripheral metabolic hormones and how these regulatory circuits regulate food intake, body weight, hepatic lipid and glucose metabolism in normal physiology and obesity
Abstract:
Obesity develops with chronic consumption of palatable energy-dense diets, and also with increasing age. With persistent positive energy balance, the increase in body weight is accompanied by a steady rise in circulating leptin levels, indicating the progressive development of counter regulatory mechanisms to antagonize leptin's anorexigenic effects. Hypothalamic neurons co-expressing agouti-related peptide (AgRP) and neuropeptide Y are direct leptin targets. We have recently shown that AgRP neurons are the predominant cell type situated outside the blood-brain barrier in the mediobasal hypothalamus. AgRP neurons are able to sense slight changes in plasma metabolic signals, such as leptin, but they also more quickly develop cellular leptin resistance in contrast to proopiomelanocortin (POMC) and other hypothalamic neurons that remain leptin-sensitive. AgRP neurons also display age-dependent increase in innervation onto their target neurons, and this process is accelerated by chronic high-fat feeding. Our studies suggest that AgRP neurons are critical sensors for peripheral metabolic hormones and that they play a dynamic role in metabolic fine tuning in response to acute changes in nutritional status. Our studies also suggest that these neurons, with their unique anatomical relationship with the blood-brain barrier, could serve as important targets for therapeutic intervention for the treatment of metabolic disorders
Andromeda Nauli
California Northstate University, USA
Title: Characterization of the newly developed in vitro chylomicron assay and its potential applications
Time : 11:35-12:00
Biography:
Andy Nauli is an Assistant Professor in the California Northstate University. He received his Ph.D. from the University of Cincinnati in 2005. His research interests include dietary fat absorption, chylomicron biogenesis, oral lipophilic drug bioavailability, and red meat allergy. His work has received more than 440 citations and $200,000 in grant funding. He has trained more than 12 students in his laboratory; served as a reviewer for several journals, including JBC, Metabolism, AJP; chair of seed grant committee; reviewer for the American Association of Colleges of Pharmacy grants; and editorial member of several peer-reviewed journals
Abstract:
The small intestine absorbs lipophilic molecules and transports them in triglyceride-rich lipoproteins. We recently developed a cell-based model capable of producing these lipoproteins. The secreted lipoproteins, namely chylomicrons and very low-density lipoproteins, were isolated by NaCl gradient ultracentrifugation. Their triglycerides, apolipoprotein B, and particle size distribution were subsequently analyzed by enzymatic assay, ELISA/Western blot, and transmission electron microscopy, respectively. Our analysis showed that 21% of the total number of secreted lipoproteins were chylomicrons. Most of the chylomicrons had a diameter of 80-200 nm, and they contained both apolipoprotein B-48 and B-100. In addition, we were able to utilize lentivirus expression system, which is more effective than the regular transfection methods, in upregulating gene expression. Our newly developed model/assay can potentially be used to study dietary fat absorption, chylomicron biogenesis, oral lipophilic drug bioavailability, and intestinal transport of lipophilic molecules
Malinna Jusoh
Universiti Malaysia Terengganu, Malaysia
Title: Effects of gibberellin on oil accumulation, fatty acid compositions and expression of fatty acid biosynthetic genes in Chlorella vulgaris (Trebouxiophyceae)
Time : 12:00-12:25
Biography:
Malinna completed her MSc from University of Oxford, United Kingdom in 2010 and PhD last year from Universiti Malaysia Terengganu (UMT), Malaysia. Upon graduation, she works as a lecturer at the School of Fundamental Science, UMT and a junior research fellow at the Institute of Marine Biotechnology, also in UMT. Her research interest is on the fatty acid and oil production of microalgae. She has been working on the gene regulations and manipulation of growth conditions to maximize the production of lipids in microalgae
Abstract:
Gibberellin (GA) is a plant hormone that regulates many physiological processes in plants. In microalgae, GA is synthesized through a slightly different pathway from higher plant GA. Recent studies have shown that several plant hormones such as auxin and jasmonic acid influence microalgae growth and fatty acid accumulation. In this study, the effects of exogenously applied GA were investigated on the growth and total oil content of a marine microalga, Chlorella vulgaris (Trebouxiophyceae) during early stationary growth phase. Results showed that GA gradually increases the cell density of C. vulgaris to up to 42% on days after treatment (DAT)-8 and also capable of delaying the algal senescence. However, the increment in cell density did not enhance the total oil production albeit transient modification of fatty acid compositions was observed for saturated (SFA) and polyunsaturated fatty acid (PUFA). This illustrates that GA only promotes cell division and growth but not the oil accumulation. In addition, application of GA in culture medium was shown to promote transient increment of palmitic (C16:0) and stearic (C18:0) acids from DAT-4 to DAT-6 and this changes is correlated with the expression of β-ketoacyl ACP synthase I (KAS I) gene. This result verified the function of this gene in the fatty acid biosynthesis pathway to produce C16:0 fatty acid
Ifeanyichukwu Edeh
University of Birmingham, UK
Title: Application of face centered central composite design in optimization of subcritical water mediated extraction of lipid from activated sludge
Time : 12:25-12:50
Biography:
Ifeanyichukwu is a Lecturer at the University of Port Harcourt, Nigeria. He is a Petroleum Technology Development Fund (PTDF) Ph.D Scholar and a member of the Supercritical Fluid Technology Group at the University of Birmingham, United Kingdom. His research interest is in the area of using state-of-art technology to produce bioenergy from waste materials. He is almost completing a research work on “A Critical Evaluation of Utility of Subcritical Water to Support the Production of Biodiesel and Renewable Diesel from Lipid Fraction of Activated Sludge” at the University of Birmingham. He has published many papers in reputable Journals
Abstract:
Bioenergy such as biodiesel and renewable diesel can be produced from lipid extracted from a microbial biomass known as activated sludge. At the moment, low lipid yield from activated sludge compared to cooking oil and animal fat seems to affect its application in bioenergy production. There is need to find an optimization technique and extraction method which has the capacity to increase the lipid yield. In this study, subcritical water was used to break the cellular structure of activated sludge in order to release its lipid content. Face centered central composite response surface design was used to optimize lipid yield. The biomass was recovered from activated sludge slurry collected from a sewage treatment work in the UK. Subcritical water mediated extraction using activated sludge was carried out in a semi batch reactor, after which lipids were extracted from the products recovered. Lipids were characterized by high temperature gas chromatography using authentic standards. Statistical analysis of face centered central composite response surface suggested a quadratic model with R-squared 0.9444. The analysis of variance (ANOVA) showed that the model was significant and lack of fit was insignificant. The lipids from the extraction products showed a variation in the profile obtained. The maximum lipid yield 41% was obtained at the optimum conditions of temperature 80oC, time 20 min and biomass loading 1%. The lipid yield when compared to that obtained from solvent extraction without subcritical water treatment and optimization was almost seven times higher, thus offering a greater potential for renewable bioenergy production
- Lipid and Lipoprotein Metabolism, Lipids in molecular medicine
Location: Sausalito
Chair
Gerd Schmitz
University of Regensburg, Germany
Co-Chair
Ikuo Yokoyama
International University of Health and Welfare, Japan
Session Introduction
Gerd Schmitz
University of Regensburg, Germany
Title: Addition of high-density lipoprotein3 and Apo A-I antagonize the platelet storage lesion and the release of platelet extracellular vesicles
Time : 11:20-11:45
Biography:
Gerd Schmitz has completed his MD from the University of Cologne and Postdoctoral studies from the University of Münster, Germany. Until end of 2014, he was the director of the Institute of Laboatory Medicine and Transfusion Medicine at the University of Regensburg, Germany. Since then he started his own consulting company < www.lipoconsult.org >. He has published more than 350 papers in reputed journals and has been serving as an Editorial Board Member of several journals
Abstract:
During activation and senescence, platelets release increased amounts of platelet extracellular vesicles (PL-EVs). We established an in vitro model for size, proteomic, lipidomic and transcriptomic characterization of PL-EVs over 5 days in platelet concentrates to better understand the platelet storage lesion. After 5 days standard blood banking, PL-EVs were isolated by filtration and differential gradient ultracentrifugation into 5 platelet microvesicle subfractions (PL-MV F1-F5) and platelet exosomes (PL-EXs) and subjected to Nanoparticle Tracking Analysis, Flow Cytometry, proteomic/lipidomic mass spectrometry, miRNA-microarray profiling and deep sequencing. PL-EVs showed overlapping particle mean sizes of 180-260 nm, but differed significantly in composition. Less dense (F1-3), intermediate and dense (F5-EX) PL-EVs, are enriched in lipidomic and proteomic markers for plasma membrane, intracellular membranes/platelet granules and mitochondria. F1-F4 is enriched in free cholesterol, sphingomyelin(SM), dihydroSM and glycerophospholipids. F4-F5 are enriched with phosphatidylinositol, ceramides, lysophosphatidic acid, phosphatidylserine and cardiolpin species. Alpha-synuclein (81% of total expression) accumulated in F1-F2, amyloid beta precursor protein in F3-F4 (84%) and ApoE (88%) and ApoJ (92%) in F3-5. PL-EXs are enriched in lipid-raft and adhesion markers. During platelet senescence, HDL3/apoA-I significantly reduce PL-EVs by 62%, and the decrease correlates with the concentration of added apoA-I, and is mediated by SRB-I and CD36. Compared to platelets, PL-EVs enriched miRNAs related to neurodegenerative diseases. Different lipid and protein compositions of PL-EVs suggest their unique cellular origins, partly overlapping with platelet granule secretion. Dense PL-EVs might represent autophagic vesicles released during platelet activation/apoptosis and PL-EXs resemble lipid rafts, with a possible role in platelet coagulation and immunology. Segregation of alpha-synuclein and amyloid beta precursor protein, ApoE/J into less dense and dense PL-MVs, respectively, show their differential carrier role of neurological disease-related cargo. HDL3/apoA-I influences membrane homeostasis of platelets by reduction of PL-EV release during platelet senescence, improving intracellular lipid processing/vesicle transport and increasing cholesterol CE-efflux
Douglas S Conklin
State University of New York, USA
Title: Lipogenesis in HER2/neu positive breast cancer cells
Time : 11:45-12:10
Biography:
Douglas S Conklin is an Associate Professor at the Cancer Research Center at the State University of New York, University at Albany. He received his Doctoral degree at the University of Wisconsin-Madison and was a Post-doctoral fellow at Cold Spring Harbor Laboratory. His research focus is on functional genomics of cancer
Abstract:
Alterations in lipid metabolism have been reported in many types of cancer. Lipids have been implicated in a number of processes important to cancer cells. Recent work has shown that HER2/neu-positive breast cancer cells rely on a unique lipogenic Warburg-like metabolism for survival and aggressive behavior. These cells are dependent on fatty acid synthesis, show markedly increased levels of stored fats and disruption of the synthetic process results in apoptosis. The pathway is operating at its limits in HER2/neu-positive cells and addition of physiological doses of exogenous palmitate induces cell death. HER2-normal cells are not affected. Transcriptional profiling and computational analyses showed that palmitate induced functionally distinct transcriptional programs in HER2-normal MCF7 and HER2/neu-positive SKBR3 breast cancer cells. In HER2/neu-positive cells, palmitate activated an ER-stress response network and reduced HER2 and HER3 protein levels sensitizing the cells to treatment with trastuzumab. Global metabolite profiling data identified affected metabolic pathways and were integrated in a multi-omics network analysis. The growth of HER2-normal MCF7 cells was unaffected by exogenous palmitate although several species of neutral lipids increased as expected. The predominant upregulated lipid species in HER2/neu-positive SKBR3 cells was the novel bioactive lipid N-palmitoylglycine. In addition, the cells exhibited AMPK activation, inhibition of fatty acid synthesis and significantly altered glutamine, glucose and serine/glycine metabolism. Limiting the availability of glutamine significantly ameliorated the lipotoxic effects of palmitate reversing the transcriptional effects. Our results indicate that the lipogenic phenotype of HER2/neu-positive breast cancer cells places metabolic constraints on HER2-mediated oncogenic signaling and therapy
Frances T Yen
University of Lorraine, France
Title: The lipolysis stimulated lipoprotein receptor, LSR, as molecular link explaining the link between dyslipidemia, obesity and neurodegenerative diseases
Time : 12:10-12:35
Biography:
Frances T Yen completed her PhD in Nutritional Biochemistry at the University of Illinois at Urbana-Champaign, and her Postdoctoral studies at Columbia University College of Physicians and Surgeons in New York and Louisiana State University Medical Center in New Orleans. She is a Director of research at INSERM, and is currently team leader of BFLA (Bioavailability and functionnalities of dietary lipids) of the URAFPA laboratory at the University of Lorraine. She has published over 30 papers in reputable journals, is co-inventor of 10 patents, and has served as reviewer for journals including Diabetes and PloS One
Abstract:
Dyslipidemia is often associated with obesity, and together represent significant risk factors for age-related diseases including cardiovascular, metabolic and neurodegenerative disorders. Lipoproteins provide the means by which lipid status is maintained through a number of complex regulatory pathways that involve lipoprotein receptors, enzymes, transporters, and transfer proteins. We have demonstrated the role of the lipolysis stimulated lipoprotein receptor, LSR in the removal of triglyceride (TG)-rich lipoproteins from the circulation during the post-prandial phase. Partial reduction of expression of LSR in LSR+/- mice leads to increased postprandial TG levels, as well as decreased capacity for the removal of lipid particles from the plasma. Furthermore, these moderately hyperlipidemic mice demonstrate higher weight gain as compared to their control littermates either with age, or when placed on a high-fat diet. When aged mice were subjected to amyloid stress by intracerebroventricular injection of the oligomeric form of β-amyloid peptide (Aβ), behaviorial and biochemical analyses revealed increased deleterious effects in LSR+/- mice as compared to their control littermates. Furthermore, Aβ-induced changes in cortical cholesterol content were negatively correlated with the behaviorial changes measured. Immunohistochemical and GC MS analyses revealed potential changes in brain membrane cholesterol trafficking and metabolism which may be the underlying reason for the increased susceptibility of LSR+/- mice to Aβ peptdies. We therefore conclude that LSR and its dependent pathways may provide the missing link to explain the increased risk of neurodegenerative diseases associated with dyslipidemia and obesity, and may prove to be useful therapeutical targets for preventive and curative treatments
Nilay V Patel
California State University, Fullerton, USA
Title: Inhibition of cholesterol synthesis increases secretion of apolipoprotein E (apoE) from human astrocytoma and liver hepatocyte cells
Time : 12:35-13:00
Biography:
Nilay Patel received his Ph. D. in Neurobiology and Behavior from SUNY Stony Brook. He was a post-doctoral fellow in Dr. Caleb Finch’s group at USC, and a Beckman Research Fellow in Dr. Barry Forman’s group at City of Hope. He is an Associate Professor in Department of Biological Science at California State University, Fullerton, and Director of CIRM-funded Bridges to Stem Cell Research. His research focuses on identification of novel regulators of apoE gene expression
Abstract:
Apolipoprotein E (apoE) genotype is the biggest genetic risk factor Alzheimer’s disease (AD). ApoE is the primary lipid carrier in the brain, and is involved in brain cholesterol homeostasis and neuronal repair. It is thought that the e4 isoform increases risk for AD due to inadequate neuronal repair capabilities, and other deleterious effects such as lysosomal dysfunction and aggregation with Abeta peptide. Apomine and simvastatin are potent cholesterol-reducing compounds that mediates their actions through inhibition of HMGCoA-reductase and activation of SREBP2. We have found that under serum-free conditions, these two compounds increase apoE secretion and increase expression of LDLR and ApoER2 (apoE receptors) from human HepG2 liver hepatocyte cells. Addition of LDL to these treatments in serum-free medium suppressed induction of apoE by these compounds. Consistently, we found a strong negative correlation between cellular cholesterol levels and secreted apoE. Our results suggest that apomine and simvastatin regulate apoE expression at both the transcriptional and post-translational levels, and that these effects seem to be indirectly through alterations in cholesterol levels
Myung-Sook Choi
Kyungpook National University, Korea
Title: Green tea extract supplement enhances insulin sensitivity via regulation of plasma adipokine levels and transcriptional response in diet-induced obesity mice
Time : 14:00-14:25
Biography:
Myung-Sook Choi has completed his PhD in Texas Woman’s University, and Post-doctoral studies in North Texas State University and Cincinnati University. She is a Professor in Department of Food Science and Nutrition and the Director of Center of Food and Nutritional Genomics in Kyungpook National University. She has published more than 220 papers in international journals on nutrition and medicine and has been serving as an Editorial Board Member of several international journals
Abstract:
Obesity-induced inflammation play a pathogenic role in development of insulin resistance, and various adipokines are linked to inflammation. Green tea, one of oriental herbal teas, is well known to have beneficial effects on obesity. However, changes in transcriptional profiles in response to green tea are little known and still needs to be elucidated. In the present study, we investigated the effect of green tea extract (GT) on phenotype characteristics and elucidated anti-obesity mechanism based on RNA-sequencing analysis of transcriptomic profiles in an animal model of diet-induced obesity. C57BL/6J mice (4-week-old, Male) were fed a normal diet (16.58% kcal from fat, ND), high-fat diet (60% kcal from fat, HFD), and HFD supplemented with 0.25% (w/w) GT. They were given free access to food and distilled water for 12 weeks. GT supplement significantly decreased fat mass, body weight as well as plasma of triglycerides, cholesterol, and HDL-cholesterol levels compared to HFD group. Also, GT decreased plasma glucose, insulin resistance index (HOMA-IR) and improved glucose tolerance. GT led significant decrease in plasma leptine, IL-6, TNF-alpha, MCP-1, IFN-gamma levels and leptin:adiponectine ratio. Moreover, mRNA sequencing analysis revealed that GT improved insulin resistance by up-regulating glucose transporter type 4(GLUT4) gene expression in epididymal WAT. In addition, GT up-regulated genes involved in glucose metabolism and lipid metabolism, such as IRS, PECK, HSL, ACC, SCD1 and SREBP1c. Together, our findings suggest that green tea is one of bioactive material for improving HFD-induced insulin resistance by regulating glucose metabolism and plasma adipokines levels as well as expression of inflammation-related gene
Mohammad-Saeid Jami
Shahrekord University of Medical Sciences, Iran
Title: Proteomic analyses reveal distinct roles for L DOPA and Edaravone in protection of neurons against oxidative stress in
Time : 14:25-14:50
Biography:
Mohammad Saeid Jami has a PhD in molecular biology and biotechnology from the University of Leon (Spain). He has also been performing postdoc researches since 2011. He is assistant proffesor at Shahrekord University of Medical Sciences, School of Medicine. He has published more than 12 papers in the field of molecular biology and has been serving as an editorial board member of CCO and JMBR
Abstract:
Parkinson's disease (PD) is the second most common neurodegenerative movement disorder caused by preferential dopaminergic neuronal cell death in the substantia nigra, a process also influenced by oxidative stress. L-3,4-dihydroxyphenylalanine (L-DOPA) represents the main treatment route for motor symptoms associated with PD. Although L-DOPA has no direct antioxidant function, L-DOPA itself may induce low level of oxidative stress that in turn stimulates endogenous antioxidant mechanisms. Conversely, 3-methyl-1-phenyl-2-pyrazolin-5-one (Edaravone) is a neuroprotective suplement that act as potent antioxidants protecting against oxidative stress and neuronal apoptosis. In this study we performed a two-dimensional gel electrophoresis (2DE)-based proteomic study to gain further insight into the mechanism in which L-DOPA or Edaravone can influence the toxic effects of H2O2 in neuronal cells. We observed that oxidative stress affects the metabolic routes as well as cytoskeletal integrity and that neuronal cells respond to oxidative conditions by enhancing numerous survival pathways. We further show that L-DOPA and Edaravone have distinctive effects in response to oxidative stress. Exposure to L-DOPA can aid hypoxia condition in cells and therefore induction of ORP150 with its concomitant cytoprotective effects. Edaravone appears to protect neuronal cells against oxidative stress via induction of Peroxiredoxin-2 and inhibition of apoptosis. Our study sheds light on the molecular interplay linking together oxidative stress, L-DOPA and Edaravone in neuronal cells
Sandra Buratta
University of Perugia, Italy
Title: Oncogene-induced senescence modify lipid composition of exosomes released from H-RasV12 expressing cells
Time : 14:50-15:15
Biography:
Sandra Buratta is a permanent researcher at the Department of Chemistry, Biology and Biotecnhology, University of Perugia, Italy. In the last decade her research focused on several aspects of phospholipid metabolism, with the main aim to define the role of enzymes involved in the biosynthesis and replacement of membrane phospholipids in several cellular processes. Particular attention has dedicated to the role of phosphatidylserine and of the enzymes of its metabolism in signal transduction and apoptosis. Her present research focus on cellular effect associated to drug-induced phospholipidosis and on the role of lipids in exosomes fate and bioactivity
Abstract:
Cell proliferation induced by oncogene activation is restrained by cellular senescence, which acts as barriers in pre-neoplastic lesions. Senescent cells show proliferation arrest, flat morphology, activation of senescent associated β-galactosidase and acquisition of a specific secretory phenotype. Exosomes, 30-100 nm extracellular vesicles derived from the endosomal system, have been recently implicated in a variety of biological processes including the transfer senescence signals to surrounding cells. Similar to proteins and miRNA, lipid species enriched in exosomes are different to those of parental cells. A detailed analysis of exosomal lipid composition could be useful to understand the role of lipids in the functional response of target cells resulting in a senescent phenotype. In this study, lipid profile of human fibroblasts transfected with H-RasV12 and their released exosomes was analyzed by LC-MS/MS and GC-MS, and compared to mock transfected cells and their released exosomes. Results showed alteration in cell lipid composition during senescence. Relative quantification and comparison of exosomes versus the corresponding cell lipid profiles reveals an enrichment of lysophosphatidylcholine, ether-phosphatidylcholine (PCether) and sphyngomyelin (SM). Furthermore, remodeling and changes in the amount of specific lipid species of diacyl-PC, PCether and SM in exosomes released by senescent cells were detected. Overall results confirmed that lipid composition of exosomes is distinct from parental cells. Moreover, an increased release of exosomes with specific lipid composition was shown to be associated to H-Ras-induced senescence, suggesting a specific role of exosomal lipids in the spreading of senescence signals to surrounding cells