Day 1 :
The Institute for Molecular Medicine
Keynote: Lipid Replacement Therapy for enhancing mitochondrial function and improving chronic disease symptoms and aging
Time : 10:30-11:00
Professor Garth L. Nicolson is the President, Chief Scientific Officer and Professor Emeritus at the Institute for Molecular Medicine in Huntington Beach, California. Having published over 650 medical and scientific papers, including editing 20 books, he has served on the Editorial Boards of 30 medical and scientific journals. He has won many awards, such as the Burroughs Wellcome Medal of the Royal Society of Medicine (London), Stephen Paget Award of the Metastasis Research Society, US National Cancer Institute Outstanding Investigator Award, and the Innovative Medicine Award (Canada). He is also a Colonel (Honorary) of the US Army Special Forces and a US Navy SEAL (Honorary) for his work on Armed Forces and veterans’ illnesses.
Loss of function in mitochondria, the key cell organelle responsible for cellular energy production, can result in cell death, excess fatigue and other symptoms that are common problems in almost if not every chronic disease. These include: neurodegenerative diseases , diabetes and metabolic syndrome, cardiovascular diseases, autoimmune diseases, neurobehavioral and psychiatric diseases, musculoskeletal and gastrointestinal diseases, fatiguing illnesses, cancer and chronic infections, among others. At the molecular level reduction in mitoc hondrial function occurs when there is loss of mitochondrial maintenance and inner membrane trans-membrane potential due to oxidative damage by Reactive Oxygen Species (ROS), resulting in reduced efficiency of the electron transport chain and less generation of ATP. Lipid Replacement Therapy (LRT) using an all-natural nutritional supplement mixture containing membrane glycerolphospholipids can be used to repair mitochondrial inner membrane damage, improve mitochondrial function, reverse ROS damage and increase the efficiency of the electron transport chain. Recent clinical trials have shown the benefits of Lipid Replacement Therapy in enhancing mitochondrial function, reducing fatigue and improving mood and cognition. For example, mitochondrial function and inner membrane trans-membrane potential has been enhanced by 25-35%, resulting in decreases in fatigue by 35-45% in chronically ill patients in clinical trials. LRT has also been used to reduce the adverse effects of cancer chemotherapy and improve symptoms other than fatigue in chronic illness patients.
N.C.S.R “Demokritos”, Greece
Time : 11.00:11.30
Chryssostomos Chatgilialoglu is the director of the Institute of Nanoscience and Nanotechnology in the NCSR “Demokritos” (Athens, Greece) since March 2014. From 1983, he w orked for the Consiglio Nazionale delle Ricerche (Bologna, Italy), and was Research Director from 1991 to 2014. He is the co-founder of spin-off companies Lipinutragen (Italy) and Lipinutramed (Greece). He has published over 240 papers in peer-reviewed journals, 33 book chapters, 6 patents, and 7 books (3 as author and 4 edited); Co-editor of the Encyclopedia of Radical in Chemistry, Biology and Materials (4 volumes), Wiley 2012; Co-author of the Membrane Lipidomics for Personalized Health, Wiley 2015
Fatty acid-based membrane lipidomics examines phospholipid components in connection with metab olic and nutritional issues. Indeed, fatty acid- based nutrition and nutraceuticals are essential to l ife and occupy leader positions in health market. Fatty acids are affected by stress conditions and the response occurs through two main mechanisms: i) the “chemical” response, being oxidized and trans fatty acids the most important structural changes occurring to membrane components; ii) the “remodeling” response by the activation of phospholipase enzymes (in particular PLA2 response), starting the cascade of lipid signaling so decisive for inflammatory and apoptotic consequences. Fatty acid-based membrane lipidomics responds to various metabol ic and environmental conditions and we contributed to the study of basic mechanisms of free radical and metabolic stress, modeling the effects in liposome , cellular and animal models. A strong analytical methodology for lipidomi c profiling was set-up to evidence positional and geometrical fatty acid isomers, which cannot be examined by mass spectrometry. New knowledge on the role of positional isomers has been acquired in healthy and pathological (obesity) conditions, highlighting the monounsaturated fatty acid biomarker sapienic acid (6cis-16:1) as novel biomarker. In nutrition and nutraceuticals, cis lipid geometry is essential for life, to ensure membrane fluidity and properties, and also fatty acid sources in foods must not contain the trans isomers, which are unnatural. By a suitable geometrical tr ans fatty acid library new insights will be given, showing the mono-trans isomers of the omega-3 PUFA , such as EPA and DHA, with important applications in lipid metabolism and nutraceuticals
- Lipidomics- whats next?, Fats - Cardio metabolic risks, Lipids in Signalling and Intra Cellular Trafficking
Oslo University Hospital, Norway
National Taiwan University, Taiwan
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 resea rch project on lipidomics and nutrace uticals, 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
Each organism and biological compartment has its own lipid composition, defined as the lipidome , which can be monitored by lipidomics. I n 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 membr anes 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-thr oughput 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, coordina ted 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
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
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.
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 hi gh-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 impr ove 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 abn ormalities and myelin dysfunction and supports the neurodevelopmental hypothesis of schizophrenia.
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
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.
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 conse cutive 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 significa nt difference in lipid profile was present between normotensive (NT) and hypertensive (HT) CAD patients. Conclusio n 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.
National Taiwan University, Taiwan
Time : 14:05-14:30
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.
A wide range of fatty acids, including saturated fatty acids , tran s fats and n-3 fatty acids, have been linked to the risk of cardiovascular disease. However, the relationship between various fatty aci ds and the risk cardiovascular disease varied mu ch 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 met abolic 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
Umeå University, Sweden
Time : 14:30-14:55
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
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 deve loped several LC-MS/MS protocols for these bioactive lipids from different fatty acid precursors, mai nly 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
Gunma University, Japan
Title: Eicosapentaenoic acid has improved the impaired insulin-signaling pathway of the cardiac muscle of infants
Time : 14:55-15:20
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
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 A kt-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
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
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
The effectiveness of anti-hyperlidemia therapy for preventing cardiovascular events and inducing regression of coronary artery stenosis has been demonstrated. M ulticenter trials have indicated that hydroxymethylglutaryl coenzyme A reductase inhibitors (so-c alled 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 cardi ovascular event still has limitations. This is because the ability of the statin to inhibit cholesterol production might ex ert 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.
SQ University, Oman
Time : 15:45-16:05
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
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 fu lcrum of homeostasis. Case in point, heterozygous familial hypercholesterolaemia (HeFH) a genetic disorder associated with considerable mor bidity 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 di squisition, 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 g lutamic acid domain