2^nd International Conference and Expo on Lipids: Metabolism, Nutrition & Health October 03-04, 2016 Orlando, Florida, USA

Biography:

Xi Xie completed her MSc. in food science from South China Agrcultural University, China. After graduation, She came to Canada at 2014 as a PhD. student at the Department of Food & Bioproduct Sciences, University of Saskatchewan. Her research aims at studying the molecular mechanism of DHA biosynthesis through PUFA synthase in Thraustochytrium.          

Abstract:

Thraustochytrium sp. 26185 accumulates a high level of    docosahexaenoic acid    (DHA), a nutritionally important w-3 very long chain   u   nsaturated fatty acid  (VLCPUFAs) synthesized primarily   by a polyunsaturated fatty acid (PUFA) synthase. However, the molecular mechanism of the  PUFA synthase  for positioning multiple cis-double bonds in the acyl chain remains elusive. The PUFA synthase in this species comprises t hree large subunits each with multiple catalytic domains. It was hypothesized that among these domains, ketoacylsynthase (KS) domains might be critical for retaining double bonds in the extended acyl chain. To investigate th e function of these putative KS domains, two KS domains from  Subunit A (KS-A) and from Subunit B (KS-B) of the PUFA synthase were dissected and then expressed as standalone enzymes in  Escherichia coli. The results showed that both KS-A and KS-B domains, but not the mutagenized ones could complement defective phenotypes of both E. coli FabB and FabF mutants.Overexpression of these domains in a wild type E. coli showed increases in the total fatty acid production. Successful complementation and functional expression of the embedded KS domains from the PUHA synthase in E. coli is the first step forward to study the molecular mechanism of the PUFA synthase for the biosynthesis of VLCPUFAs.

Biography:

William Hancock is completing his PhD at the University of Alabama at Birmingham School of Medicine in the Department of Cell, Developmental, and Integrative Biology. Utilizing an undergraduate background in Physics, he is pursuing a wider understanding of the impact of potent lipid derived signals in the control of transcriptional events related to physiology and pathophisiology.

Abstract:

Bone modeling is modulated by    lipid signals   , especially arachidonic acid and its metabolites. These lipid signals can be generated by    phospholipases A₂    which hydrolyze the sn-2 fatty acid substituent from membrane    phospholipids   ; cellul ar AA is esterified in this position within membrane   glycerophospholipids  . Knockout mice lacking the group VIA calcium-indepen dent phospholipases A₂ beta (iPLA₂β) exhibit an enhanced, age-related decline in cortical bone size, trabecular bone volume, and bone mineralizing surfaces. They also reveal a dramatic decrease in mineral apposition rate by 6-months of age and accelerated age-related lipid droplet accumulation in their bone marrow.  Current studies demonstrate that osteoblasts from calvaria of iPLA₂β-knockout mice express lower levels of Runx2, bone    morphogenetic protein    2, and alkaline phosphatase   mRNA  , relative to WT osteoblasts.  These findings correlate with decreased   os teoblastogenesis   and osteoblast activity, as reflected by reduced mineralization determined by Alizarin Red staining and quantification. This reduction can be rescued by the treatment of o steoblasts with  arachidonic acid  and  prostagland in  E2, a cyclo-oxygenase-catalyzed metabolite of arachidonic acid, which is hydrolysed through activation of iPLA ₂β.  Prostaglandin E2 is known to increase osteoblast replication and differentiation. Our studies indicate that induction of differentiation factors and bone mineralization occur, in part, by activation of iPLA₂β and subsequent generation of iPLA₂β-derived lipid signals.  These findings indicate a prominent role for iPLA₂β in determining  mesenchymal stem cell  fate, bone maintenance, and bone remodeling. 

Biography:

Cherryhan Salvedia Ebrahim completed her M.B.B.Ch from Cairo University. She is currently an Academic Researcher at Misr International University (MIU). She is an MSc student of Physiology at Ain Shams University, School of Medicine and anticipated completion date is October 2016. She is a Clinical Nutritionist, obtained her diploma from National Nutrition Institute. She is a Medical Supervisor at Patient Welfare department, a coordinator at the E-learning Unit and has supervised 2^nd year students for data collection of assigned researches, School of Dentistry, MIU. She is an American Heart Association certified instructor of Basic Life Support for healthcare professionals.

Abstract:

Prunus armeniaca, commonly called Apricot, is grown widely. The Mediterranean region accounts for more than 55% of the world’s production. However, little is known about their potential health benefits. Apricot is thought to be rich in antioxidants because of its flavonoids and   carotenoids   contents. The dominant sugar in fruit tissue was sucrose. Fructose is considered a factor for several adverse health effects, a stimulant of de novo lipogenesis and hepatic  lipogenesis . Recently, the prevalence of metabolic syndrome has significantly and statistically increased in parallel with the increased contribution of fructose in our diets attributing more to the sweetened beverages. This study was conducted on 36 male albino rats over 10 weeks to study the  antiox idant effect  of the extract. 10 % Fructose solution was administered to two group s to induce hyperuricemia while a dos e of 70 mg/kg/day of the extract were administered by oral gavage concurrently to on e of the two groups. The fruit was purchased and an ethanol extract was obtained by sonication and evaporation at the pharmacognosy department of Cairo University. Results were compared to the control group and supported by laboratory and histopatho logical findings. The extract group showed lower plasma TG, NO, Creatinine and Uric acid levels than the fructose group ( p value <0.001). NO and Creatinine were significantly higher than the control group (p value <0.001). Conclusion: The associating low NO and UA levels with the extract support its antioxidant and hypouricemic potentials.

Biography:

Ominyi Chidimma Emmanuel is running his M.Sc at Michael Okpara University of Agriculture, Umudike Nigeria. He is a staff of Akanu Ibiam Federal Polytechnic, Unwana Nigeria. He has published about 5 (five) papers on reputed journals and presented about 6 (six) paper in conferences.

Abstract:

Oil was extracted from Chrysophyllum albidum seed using petroleum  ether  as solvent. The yield of the oil was found to be 4.9%. The result of characterization of the oil extract showed that it has iodine value of 163.3mg, Saponification value of 90.71mg, Acid value of  19.70 mg, Percentage Free Fatty Acid of 9.90% and Dirt content  of 0.23%. The specific gravity of the oil at 25⁰C and its content was found to be 0.8269 and 10.00% respectively. The color analysis gave Red, Yellow, Blue and Neutral to be 1, 1, 2, 2, 2, 1 and 0,0 respectively. Thus the oil was found to be a drying oil. The Fatty Acid Profile of the oil was also determined with the aid of  gas liquid chromatography  used fatty acids in methyl esters and was found to have Oleic Acid (C18:1) as the predominant fatty acid having an area of 10.10125%.  It was also found to contain Alpha Linoleic Acid (omega-3) and Linoleic Acid (omega-6) which are essential to the human body but cannot be synthesized by its metabolic processes. 

Biography:

H L Nadaf has completed his PhD from University of Agricultural Sciences, Dharwad and Post-doctoral research from Texas A & M University, College Station, Texas, USA. He is the Principal Scientist (Plant Breeding) and Head of AICRP on Groundnut, UAS, Dharwad. He has published more than 75 papers in reputed journals.

Abstract:

Groundnut is an important oilseed crop in India wherein majority of the produce is crushed for edible oil. Narrow genetic base of groundnut has impeded its genetic improvement in yield and oil quality. In order to induce genetic variation and diversify the source of high oleate trait in groundnut, GPBD 4 (inter-specific derivative), a popular cultivar with inherent resistance to major foliar disease (late leaf spot and rust) was subjected to mutagenesis (EMS and gamma rays). A significant variation in fatty acid profile of mutant progenies was observed in M4 generation. Two stable high oleic (>70%) mutant lines viz., GM6-1 and GM4-3 were isolated and utilized for characterization of FAD 2B gene that control oleic and linoleic acid content in seeds. Cloning and sequencing of FAD 2B gene from parent GPBD 4, GM6-1 and GM4-3 revealed two novel mutations (1085A→G and 1111G→A) in GM 6-1 and single transition 1111G→A in GM 4-3. A CAPS (bF19/R1, Mob II enzyme) marker and two SNP (bF19/GM6-1-GM4-3 and bF19/GM6-1) markers that could differentiate the two mutants were developed and tested. These makers were also validated in other high and low oleic genotypes. Some of the RILs derived from TMV 2 × GM 6-1 that were high in oleic acid with resistance to LLS and rust were tested using IPAHM103 and GM2301 markers linked to a common genomic region governing rust and LLS resistance. Thus, these new high oleic mutant lines with resistance to major foliar diseases could help to broaden the genetic base as valuable genetic resources in future groundnut breeding programs.

Biography:

Ademola Ayeleso has completed his Doctoral degree in the Department of Biomedical Sciences, Cape Peninsula University of Technology, South Africa in 2013. He is presently a Post-doctoral Research Fellow under the headship of Prof. Emmanuel Mukwevho at the North-West University, South Africa. His research has focused more on therapeutic approaches to the management of diabetes mellitus.

Abstract:

Activation of calmodulin dependent protein kinase (CaMK)II has beneficial roles in metabolism and health. Lipid droplets inhibit insulin-sensitive glucose transporters, accounting for insulin resistance in type 2 diabetes. ATP synthesis in the mitochondria is also decreased in type 2 diabetes subjects. The aim of the study was to examine the role of (CaMK)II activation on lipid droplets and mitochondria function in rat skeletal muscle. Induction of (CaMK)II in the male Wistar rats was done through exercise and the inhibition of exercise-induced (CaMK)II was achieved by administration of KN93. Gastrocnemius muscles were extracted from rats in the control, exercise and exercise + KN93 groups. Transmission electron microscopy (TEM) was used to determine lipid droplet size/number and mitochondria size. ATP synthesis was done using CellTiter-Glo luminescent assay. The results showed that exercise-induced (CaMK)II activation significantly decreased lipid droplet size and number. There was also a significant increase in the mitochondrial size and ATP synthesis due exercise-induced (CaMK)II activation. In conclusion, the study showed that exercise through the induction (CaMK)II can help to regulate lipid droplets formation and improve mitochondria function. Hence, may help to reduce risk of type 2 diabetes and obesity.

Biography:

Chunfa Huang has completed his PhD from Xiamen University and postdoctoral studies at Wake Forest University School of Medicine and University of Texas Southwestern Medical Center. He was highly trained in  lipid metabolism  and cell signaling as a graduate student and as a post-doctor. Over the decades, his research area focuses on defining novel signaling pathways that regulate lipid metabolism and that are associated with human diseases including cancer., and has published more than 50 papers in reputed journals. 

Abstract:

      Cholesterol       plays an important role in cancer de velopment,      drug resistance      and chemoi mmuno-sensitivity.      Statins     , cholesterol lowering drugs, can induce apoptosis, but also negatively interfere wit h CD-20 and rituximab-mediated activity. Our goal is to identify the alternative targets that could reduce cholesterol levels but do not interfere with CD-20 in chemo      immunotherapy      of chronic lymphocytic leukemia (CLL). We used MEC-2 cells, a CLL cell line, and the peripheral blood     mononuclear     cells (PBMCs) from    CLL    patients, treated them with cholesterol lowering agents, and analyzed the effect of these agents on cholesterol le vels, CD-20 expression and distribution, a nd cell viability in the presence or absence of fludarabine,    rituximab    or their combinations. We found that MEC-2 cells treated with cholesterol lowering  agents (BIBB-515, YM-53601 or TAK-475) reduced 20% of total cellular   cholesterol   levels, but also significantly promoted CD-20 surface expression. Furt hermore, treatment of cells with fludarabine, rituximab or their combinations in the presence of BIBB-515, YM-53601 or TAK-475 enhanced MEC-2 cell chemoimmuno-sensitivity measured by cell viability. More importantly, these cholesterol lowering agents also significantly enhanced   chemoimmuno-sensitivity   of the PBMCs from CLL patients. Our data demonstrate that BIBB-515, YM53601 and TAK-475 render chemoimmuno-therapy resistant MEC-2 cells sensitive to chemoimmuno-therapy and enhance CLL cell chemoimmuno-sensitivity without CD-20  epitope  presentation or its downstream signaling. These results provide a n   ovel strategy which could be applied to CLL treatment.

Biography:

Ian James Martins is a reviewer for various journals and was appointed as the Chief Editor for Scientific and Academic Publishing (2013/2014). Research Gate’s analysis of Dr Martins publication stats places the RG score higher than 93% of the international researchers. Dr Martins is a Fellow at Edith Cowan University/Honorary Senior Fellow (University Western Australia). Over eating and prevention by food restriction improves liver   lipid metabolism   and nature of  fat  consumed is important to improving health with contribution to biology of food restriction and maintenance of the peripheral sink abeta hypothesis and its relevance  to organ suicide, diabetes and Alzheimer’s d isease.  

Abstract:

Interventions to the aging process involve early calorie restriction with appetite regulation connected to appropriate genetic mechanisms that involve mitochondrial    biogenesis    and   DNA repair   in cells. In the aging process as the anti-aging genes are suppressed as a result of transcriptional dysregulation chronic disease accelerates and is connected to insulin res istance and   neurodegenerative  . Interests in the gene-environment interaction indicate that the anti-aging gene Sirtuin 1 (Sirt 1) that regulates food intake has been repressed early in the aging process in various global populations. The connections between Sirt 1 and other anti-aging genes such as Klotho, p66shc (longevity protein) and Forkhead box proteins (FOXO1/FO XO3a) have been connected to  lipid metabolism  and alterations in these ant i-aging genes regulate glucose, lipid and amyloid beta metabolism. Appetite regulation by nutritional intervention is required early in life that involves Sirt 1 circadian clock gene expression with Sirt 1 maintenance of other cellular anti-aging genes involved in cell metabolism and  apoptosis . Interests in anti-aging therapy with appetite regulation improves an individual’s survival to metabolic disease induced by gene-environment interactions by maintenance of the anti-aging genes connected to the metabolism of cholesterol, bacterial lipopolysaccharides, drugs and xenobiotics.  

Biography:

In December 2012, Mesut got his PhD degree from Christer S. Ejsing's lipidomics lab at University of Southern Denmark. Here he developed quantitative shotgun  lipidomics  platform for functional studies of yeast and mammalian cells lipidome. Right, after that he joined Andrej Shevchonko's lab MPI-CBG, Dresden Germany. Here he continued his work on shotgun lipidomics and additionally he deve loped a LC-MS based platform for quantification and discovery of endocannabinoids, small lipids. In 2015, he got offered to start a lipidomics lab at Danish Cancer Society Research Center (DCRC) and since 2015 he has been head of Lipidomics Core Facility (LCF) at DCRC.

Abstract:

  Lipids   are essential molecules of every living organism. Lipids assemble bilayers, determine the architectu re of  cellular  membr anes, and orchestrate numerous biological processes. Every living organism is equipped with m etabolic pathways that produce structurally and functionally highly diverse lipid species. The manners of regulations in lipid  metabolism  are poorly illuminated, yet of pivotal importance since imbalance in the lipid metabolism has been linked to pathophysiology o  f numerous diseases. The lipidome – the lipid repertoire of biological materials – includes species that differ in types of head groups, presence, length, and number of  fatty acyl  chains, numbers and positions of double bonds, and presence of additional modifications such as glycosylation and hydroxylation  etc. Obviously the combination of these gives rise to thousands of lipid species. Lipidomics methodologies enable to monitor lipid metabolism via systematic and quantitative measurements of individual lipid species in complex mixtures. Here, we present the shotgun lipidomics methodology, an advanced  mass spectrometry -based approach that enables absolute quantification. Shotgun lipidomics allows in a single setup to identify and quantify hundreds of lipid species belonging to 15-20 lipid classes. In brief, sample lipids are extracted into organic solvents and directly infused into  mass spectrometer  via electrospray ionizatio n. Lipids are separated and identified based on the unique mass to charge  ratios of their ions and fragmentation patterns, and absolutely and accurately quantified against internal standards. The simple and robust setup makes this approach particularly suited for high throughput lipidomics analysis. The typical workflow, challenges, and considerations on the shotgun lipidomics will be highlighted.

Biography:

Marica Bakovic completed BSc in Chemistry and PhD in     Biological Chemistry     at the University of Alberta. She received post-doctoral awards from Medical Research Council and Alberta Heritage Foundation. Before com ing to the University of Guelph, she worked in the area of molecular and    cell biology    of   lipid   metabolism at the Faculty of Medicine, University of Alberta. C  urrently, she is Professor in the Department of   Human Health   and  Nutritional Sciences  at the University of Guelph. Dr. Bakovic has a long-lasting  interest in lipid metabolism and nutrition, especially in the area of regulation of membrane phospholipids,  fatty acids , and methyl-group donors.  

Abstract:

Phospholipids play an indispensable role in heart function via their structural and metabolic roles, and serve as a barrier that protects the intracellular cell environment.  The first evidence of mammalian heart dysfunction in relation to deregulated phospholipid synthesis by the CDP-ethanolamine Kennedy pathway came from our recent study with CTP: phosphoethanolamine cytidylyltransferase (Pcyt2) heterozygous mice ETKO. ETKO mice of both genders have reduced phosphatydylethnolamine (PE) synthesis and turnover, accumulate plasma and tissue triglycerides and develop insulin resistance. However, only ETKO males develop age-related cardiac hypertrophy and hypertension. The underlying mechanism for the male specific dysfunction was identified in the accumulation of arachidonic acid and other n-6 elongation/desaturation pathway intermediates in the male heart membranes and reduced circulating testosterone levels. There is a clear sexual dimorphism in the heart phospholipids and the sex-related differences expand to the heart neutral lipids but not cardiolipin. Dysfunctional Pcyt2 gene (reduced PE synthesis and turnover) causes insulin resistance in both males and females, however specifically perturbs membrane metabolism protecting the female heart and causing the male-specific diabetic cardiomyopathy. We explore the nature of those differences to show what role Pcyt2 plays in cardiac cell function, signaling, and gene expression and how they contribute the male-specific hypertension and heart pathology.

Biography:

Sampath Parthasarathy MBA, PhD , was instrumental in the development of the concept of oxidized   LDL   and its contribution to  atherosclerosis , a major form of cardiovascular disease. He is currently at University of Centr al Florida as the F lorida Hospital Chair in Cardiovascular Sciences and the Associate Dean of Research. Dr. Parthasarathy has published over 250 articles and has served on numerous editorial boards and NIH committees. He has been continuously funded by NIH and other agencies for over 30 years and he was awarded the distinguished service Award by the American Heart Association and by the American Association of Cardiologists of Indian Origin and from SASAT International. He is also the recipient of the prestigious van Deenen Memorial award for lipids and the Ranbaxy Award for excellence in cardiovascular research.
 

Abstract:

Apolipoprotein (Apo A1) and apolipoprotein E (Apo E) mimetic peptides have attracted attention due to their ability to reduce atherosclerosis and exhibit antioxidant, anti-inflammatory, and hypolipidemic properties. Based on the nature of the peptide, we predicted that these effects could be attributed to their positively charged amino acid residues and hydrophobicity. Accordingly, we designed and tested whether three distinct and unrelated cationic peptides would inhibit the oxidation of lipoproteins, neutralize the charge of negatively charged modified lipoproteins, and inhibit the latter’s uptake by macrophages. As bacterial lipopolysaccharide (LPS) is also a highly negatively charged molecule, we also tested the peptides to affect LPS induced macrophage inflammatory response. 

5F-mimetic peptide of apoA1, LL27 derived from the anti-microbial peptide CAMP, and a human glycodelin derived peptide was commercially synthesized. The number of positively charged amino acid residues (K+R) and negatively charged residues (D+E) were 4/4, 7/4, 6/2 respectively. Their abilities to reduce lipid peroxides (LOOH), inhibit the oxidation lipoproteins (LDL & HDL), interact with modified lipoproteins, and to inhibit macrophage uptake of modified LDL and inflammation were analyzed.  Their abilities to inhibit LPS and Ox-LDL induced inflammatory responses also were determined.

Cationic peptides decomposed 13-HPODE and inhibited the oxidation of LDL in a lysine dependent manner. Incubation of Ox-LDL and Ac-LDL with the peptides resulted in charge neutralization. Pre-incubation of the peptides with modified lipoproteins reduced the uptake of the latter by macrophages and foam cell formation as detected by Oil-Red O staining. Increased inflammatory gene expressions were observed in the presence of LPS/Ox-LDL. However, peptides inhibited the Ox-LDL-induced inflammatory gene expressions but showed a dual effect on LPS induced inflammatory response. In contrast, native LDL, which has several positively charged domain formed complexes with Ox-LDL and increased macrophage cholesterol accumulation.

Based on these studies, we suggest that cationic peptides may be a valuable tool for controlling Ox-LDL mediated inflammation and atherosclerotic progression. However, the Ox-LDL, in the presence of native LDL might be more atherogenic and suggest a potential competition between soluble peptides and intact lipoproteins.

Biography:

Sandile Fuku completed his Doctoral studies in   Biomedical   Technology from the Central University of Technology and  is currently a Postdoctoral fellow in the Department of  Biochemistry,  at North-West University. Currently, his research is on  epigenetic regulation in metabolic syndromes, particularly focusing on  diabetics  and cancer. He has published work in cancer treatment, diabates and phytochemistry  .

Abstract:

Background

Activation of Calmodulin dependent protein kinase (CaMK)II by exercise has plethora of benefits in metabolism and health.  Regulation of lipid metabolism is very significant to alleviate type 2  diabetes and obesity.  The role of CaMKII in the regulation of genes that are involved in lipid metabolism has not been studied yet, which became the focus of this study.

Methods

Five to six weeks old male Wistar rats were used in this study.  Western blot was performed to assess the protein expression of Carnitine palmitoyltransferase (CPT)-1 and Acetyl-CoA carboxylase (ACC)-1.  Cpt-1 and Acc-1 gene expressions were assessed using Quantitative real time PCR (qPCR).    

Results

The results indicate that exercise-induced   CaMKII   activation increases CPT-1  expression   and decreases ACC-1 expression in rat skeletal m  uscle.  Thus, confirming CaMKII activation by exercise and the resultant increase in  lipid  oxidation.     Administration of KN93 (CaMKII inhibitor) reversed all exercise-induced changes.  

Conclusions

This study demonstrated that CaMKII activation, by exercise, regulates lipid    metabolism      genes   in rat ske letal  muscle .  Fur ther, the increase in lipid oxidation and decrease in   lipi d   synthesis are evidence of the regulatory role CaMKII in lipid metabolism. CaMKII is a potential target in designing novel   therapeutic   drugs in the management and treatment of  type 2 diabetes  and obesity.  

Biography:

Abstract:

The burden of    cardiovascular disease    (CVD) in Indian population is high regardless of their country of residence. World Health O rganisation estimates 60% o world’s   cardiac   patients will be Indians with 50% 0 f   CVD   related deaths occurring in patients below 70y compared to 23% in the West. Indian ethnicity is regarded as a non modifiable risk factor by CVD prevention guidelines. 

The mission of the LAI expert consensus statement on management of   dyslipidaemia   is to address early onset and higher risk for CVD in this population by simplifying the process of identification at an early age as well as to  intensify treatment to aggressively mange risk factors including life style changes at a lower risk levels compared  to other global guidelines.

The choice of a lower target of   LDL   C of <50 mg/dl and non-HDL C o <80 mg/dl for the high risk group as well as secondary prevention will help India achieve the expected reduction in CVD. Adoption of Non HDL-C a s a co primary target will address  atherogenic  lipoprotein pattern that incorpora  tes the low HDL and high Triglyceride level in this population. The consensus statement recommends a lower threshold for not using statin at <5% but the use of life time risk assessment in this group. Reducing the age threshold for screening for CVD risk to 18y (at ent ry to university education) is likely to have a greater impact in reducing the CVD epidemic.

While considerable success is seen with the effort taken by LAI to implement the advice to Indian physicians, adoption of this expert advice by governmental bodies, other professional organisation within and outside India will provide a greater impetus to reduce premature CVD in this high risk population irrespective of their place of residence.

Biography:

Laura Bindila is Head of  Lipidomics /Mass Spectrometry Facility at the Institute for Physiological Chemistry, University Medical Center Mainz, where her scie ntific interest is unravelling the lipid signals involved in various neurobiologica l processes, and more generally in physiological and pathophysiological states. She is also a member of Research Center for Translational Neuroscience, of the University of Mainz. She has previously worked at Luxembourg Clinical Proteomics, and University of Münster where she has focused on glycoconjugates an d (glyco)proteomics in cancer research and rare diseases.

Abstract:

      Lipids       are molecular components which play essential roles in many physiological processe s and      pathological      condi tions, including      neurodegenerative      , metabolic, immune diseases. The     lipids     serve not only a constitutive rol e in the cell membrane, but also as the  source for downstream signaling molecules, such as      endocannabinoids      or eicosannoids that underscore essential     neurobiological     functions. In neurobiology research lipids emerge as important cand idates for     biomarkers    , drug targets, but also as therapeutic agents. To gain a better understanding of their specific functio ns and to define the    signaling    networks, especially  under    pathological    conditions, accurate identification and quantification of lipids, as well as profiling of other molecular correlat es such as related   genes   and  proteins  in on  e and the same tis  sue source is essential. In addition, (sub)localization of disease-associated lipid changes within and across tissue regions is essential to expedite the unravellign of disease mechanisms, as well as discovery of lipid-based  drug  targets and lipid-based therapeutic agents.   

Here, advanced  lipidomic  strategies, combining quantitative mass spectrometry with high-throughput sample preparation for multiplex lipid analysis in minute amount of biological matrices, that enable translation of pr e(clinical) features of neurological disorders into quantita tive neurolipidomics will be discussed. 

Biography:

Professor Lakshman is currently the Director of Research Laboratories and the Chief of Lipid Research at the VA Medical Center, Washington, D.C. He also has joint appointments as a Professor in the Departments of  Biochemistry  & Molecular Medicine as well as in the Department of Medicine at the George Washington University, Washington, D.C. He directs studies in the areas of Alcoholism, Alcoholic Liver Disease, Oxidative Stress, Coronary Artery Disease, Lipids & Lipop roteins, Metabolic & Genetic Obesity, Hepatotoxins, Gene Regulation & Expression. He joined the National Institute of Health, to work on Alcoholic Hyperlipidemia under the able guidance of Professors Richard Veech and Nobel Laureate, Hans Krebs. In 1979, he received the prestigious VA Research Career Scientist Award working in the field of Alcohol and Alcoholism at the VA Medical Center, Washington, D.C. He was honored the “Washington Heart Ball” Research Award in 1990 in the field of Hyperlipidemia. Professor Lakshman has chaired as well as has been an invited speaker in several Symposia in International and National Meetings all over the world. He is a member of several professional societies such as American Society of Biochemistry & Molecular Biology, American Institute of Nutrition, etc.

Abstract:

    Fatty Liver     (hepatosteatosis) is the earliest abnormality in the patho genesis of    Alcoholic Steatohepatitis    (ASH) and     Non-Alcoholic Steatohepatitis    (NASH) and due either to metabolic risk factors associated with chronic alcohol abuse or with insulin resistance and /or metabolic syndrome in the absence of alcohol consumption. When unchecked, both ASH and NASH lead to    liver fibrosis   , cirrhosis,   hepatocellular carcinoma   (HCC) and eventual death. A number of common mechanisms contribute to the above various stages of hepatocyte injury in cluding   lipotoxicity  , endotoxin release, oxidative and ER stress leading to increased pro-inflammatory cytok ines that stimulate  hepatic fibrogenesis  and cirrhosis by ac tivating th e quiescent hepatic stellate cells (HSC) into myofibroblasts. Significantly, patients with either ASH or NASH respond favorably to early treatment modalities to reduce  hepatic fat  accumulation and consequent increased inflammatory signaling and activation of hepatic stellate cells. Although the pathogenic pathways associated with ASH and NASH ar e seemingly similar, differentiation of the  molecular mechanism /s of the pathogenesis of these liver diseases is critical in identifying the unique molecular signatures especially in the early diagnosis of ASH and NASH. Current clinical practice requires the invasive  biopsy procedure for the conclusive diagnosis of ASH and NASH. Micro RNAs (miRNAs) are ~22 nucleotide non-coding sequences that bind to  the 3'-untranslated region of target transcripts and regulate gene expression by degradation of target mRNAs or inhibition of translation. Emerging studies may prove to establish miRNAs   as excellent non-invasive tools for the early diagnosis of various stages of liver diseases.

Biography:

Raman Puri is working as Senior Interventional Cardiologist at IP Apollo Hospital since October 1996 and was Head of Cardiology Unit in Ram Manohar Lohia Hospital. He is the Founder and Chairman of Lipid Association of India established since 2012. He established the Department of Cardiology in Safdarjung Hospital in 1992. He has also contributed to advances in intervention. He had worked as fellow in Interventional Cardiology in Hospital Charles Nicolle, France and National Cardiovascular Center, Osaka-Japan. His work involves interventions including coronary angiographies, coronary angioplasty and stenting, valvuloplasty, device closure of the heart defects such as ASD, PDA, left atrial appendage closure for prevention of stroke in patients with atrial fibrillation and pacemaker implantation besides clinical cardiology practice. He has special interest in preventive cardiology especially dyslipidaemia and hypertension.

Abstract:

The burden of cardiovascular disease (CVD) in Indian population is high regardless of their country of residence. World Health Organisation estimates 60% of world’s cardiac patients will be Indians with 50% of CVD related deaths occurring in patients below 70 years compared to 23% in the West. Indian ethnicity is regarded as a non modifiable risk factor by CVD prevention guidelines. The mission of the LAI expert consensus statement on management of dyslipidaemia is to address early onset and higher risk for CVD in this population by simplifying the process of identification at an early age as well as to intensify treatment to aggressively mange risk factors including life style changes at a lower risk levels compared to other global guidelines. The choice of a lower target of LDL C of < 50 mg/dl and non-HDL C of < 80 mg/dl for the high risk group as well as secondary prevention will help India achieve the expected reduction in CVD. Adoption of non HDL-C as a co primary target will address atherogenic lipoprotein pattern that incorporates the low HDL and high Triglyceride level in this population. The consensus statement recommends a lower threshold for not using statin at < 5% but the use of life time risk assessment in this group. Reducing the age threshold for screening for CVD risk to 18 years (at entry to university education) is likely to have a greater impact in reducing the CVD epidemic. While considerable success is seen with the effort taken by LAI to implement the advice to Indian physicians, adoption of this expert advice by governmental bodies, other professional organisation within and outside India will provide a greater impetus to reduce premature CVD in this high risk population irrespective of their place of residence.

Biography:

Dr. Siddiqi is an Associate Professor at the UCF College of  Medicine  and earned his Ph.D. at Central Drug Research Institute/Lucknow University i n India. He did post-doctoral training at the National Institute of Immunology in India and the Gastroenterology Division, University of Tennessee  Health Science Center. His research is focused on deciphering the cellular and molecular mechanisms underlying the lipid metabolism. His major contribution to the field is the discovery of a new paradigm for the ER-to-Golgi transport of nascent lipoproteins. He serves on editorial boards of several journals and as a reviewer for numerous journals.  
 

Abstract:

Secretion of   lipids   in the form of very low-density lipoproteins (VLDL) by the liver plays an important role in maintaining  overall body lipid  homeostasis . Any abnormality a ssociated with this physiological process can lead to severe metabolic disorders such as  hyperlipidemia , hepatic steatosis etc. The rate-limiting step in the secretion of VLDLs from the liver is their transport from the endoplasmic reticulum (ER) to the Golgi and represents a  potential therapeutic target in controlling VLDL secretion. We have identified a distinct ER-derived vesicle, VLDL transport vesicle (VTV), which facilitates the targeted delivery of VLDLs from the ER to the Golgi. To find out the factors that regulate the biogenesis of these vesicles, we performed detailed proteomic and  biochemical  analyses. Our data revealed that two small Mr proteins, cideB and SVIP are present in VTV but not in other ER-derived vesicles. Our morphological and co-immunoprecipitation data revealed that both cideB and SVIP specifically interact with VLDL  structural protein , apolipoproteinB100. To examine the roles of these proteins in VTV-biogenesis, we carried out an in vitro ER-budding assay. We show that either blocking or knockdown of cideB and SVIP abrogates VTV-budding and VLDL secretion from  hepatocytes . We conclude that cideB and SVIP control VLDL/lipid secretion from the liver by regulating VTV-formation and their identification is critical for the development of novel therapeutics for dyslipide mia.

Biography:

Michal Masternak has completed his PhD at the age of 26 years from Poznan University of  Medical Sciences  and postdoctoral studies from Southern Illinois University, School of Medicine in Springfield , IL. He is an Associate Professor at Univerist of Central Florida. He has published more  than 76 papers in reputed journals and has been serving as an editorial board member in several scientific journals.

Abstract:

Studies of mice with growth hormone (GH) deficiency or resistance have shown that disruption of the GH axis promotes     insulin     sensitivity, improves    glucose metabolism    and is strongly associated with extended longevity and delayed aging. Long-living GH receptor knockout (GHRKO) and GH-defic ient Ames dwarf (df/df) mice are    obese    and more importantly have more visceral fat than their normal counterparts, yet these mice are still very insulin sensitive. Interes tingly, our data showed that surgical   visceral fat   removal (VFR) decreased  insulin  sensi  tivity and glucose tolerance in long-living, obese GHRKO and df/df mice in comparison to sham controls, while the same intervention improved insulin sensitivity and glucose tolerance in N mice. Additionally, VFR intervention improved insulin signaling p athway in skeletal muscle in normal mice only, without any alterations in GHRKO animals. We also found that the transplant of visceral fat from GHRKO mice to N mice (N-GHRKO) improved whole body insulin sensitivity when comparing with  sham-operated  mice (N-S) and with mice that received visceral fat from N mice (N-N). Observed improvement of insulin sensitivity was associated to increased phosphorylation levels of insulin receptor and increased expression of  Pparα and Pparγ in the liver.These findings show that the same endocrine organ plays different role on insulin sensitivity in GHRKO and df/df mice when comparing with N control mice. We hypothesize that this divergent role of VF is due to different secretory pattern in visceral fat, which is mediated by suppression of GH action in adipose tissue.

Biography:

Sampath Parthasarathy MBA, PhD , was instrumental in the development of the concept of oxidized LDL and its contribution to   atherosclerosis  , a major form of  cardiovascular disease . He is currently at University of Central Florida as the Florida Hospital Chair in Cardiovascular Sciences and the Associate Dean of Resea rch. Dr. Parthasarathy has published over 250 articles and has served on numerous editorial boards and NIH committees. He has been continuously funded by NIH and other agencies for over 30 years and he was awarded the distinguished service Award by the American Heart Association and by the American Association of Cardiologists of Indian Origin and from SASAT International. He is also the recipient of the prestigious van Deenen Memorial award for  lipids  and the Ranbaxy Award for excellence in cardiovascular research. 

Abstract:

Generation of foam cells, an essential step for reverse   cholesterol   transport (RCT) studies, uses the technique of  receptor dependent macrophage loading with radiolabeled acetylated  Low Density Lipoprotein  (Ac-LDL). In this study, we used the ability of a biologically rel evant detergent molecule,  Lysophosphatidylcholine  (Lyso PtdCho), to form mixed micelles with cholesterol or cholesteryl ester (CE) to generate macrophage foam cells. Fluorescent or radiolabelled cholesterol / Lyso PtdCho mixed micelles were prepared and incubated with RAW 264.7 or mouse peritoneal macrophages. Macrophag es incubated with  cholesterol  or CE (unlabeled, fluorescently labeled or radiolabeled) / Lyso PtdCho mixed micelles accumulated CE  as documented by microscopy, lipid staining, labeled oleate incorporatio n, and by thin layer chromatography (TLC). Such foam cells unloaded cholesterol when incubated with high density lipoprotein (HDL) and not with oxidized HDL (Ox-HDL). We propose that stable cholesterol or CE / Lyso PtdCho micelles would offer advantages over existing methods.

Using this technique we demonstrated that such macrophages mimicked biological properties attributed to  cholesterol  loaded macrophages. Earlier, we had used similar technique to enrich cells with beta carotene. We suggest that this novel technique of delivering macromolecules to the cells could be further manipulated to de liver other hydrophobic large molecular cargos to the cells.

Biography:

Edward A Dennis is a distinguished Professor of Chemistry and Biochemistry and of Pharmacology in the School of Medicine at the University of California at San Diego (UCSD). He received his BA from Yale and a PhD from Harvard and was a Post-doctoral fellow at Harvard Medical School. He has served as Chair of the Department of Chemistry and Biochemistry. His research focus has been on the mechanism of the enzyme phospholipase A₂, signal transduction, inflammation, lipid metabolism, eicosanoid action, and lipidomics. He authored over 380 publications, is Editor-in-Chief of the Journal of Lipid Research and Director of the LIPID MAPS Consortium.

Abstract:

The phospholipase A₂ (PLA₂) superfamily exhibits a large array of functions, but of special interest is the inflammatory cascade which is initiated by the release of free arachidonic acid by some types of phospholipase A₂, all of which interact with membrane phospholipids. However, different PLA₂ types have unique three-dimensional structures and unique catalytic residues as well as specific tissue localization, distinct biological functions, and with which membrane phospholipids have unique allosteric interactions. Understanding how the different PLA₂s associate with phospholipid membranes, specific phospholipid substrate molecules, and inhibitors on a structural and molecular basis has advanced in recent years due to the introduction of hydrogen/deuterium exchange mass spectrometry approaches. We will emphasize recent results utilyzing hydrogen/deuterium exchange approaches and molecular dynamics on the major types of PLA₂, including secretory s-PLA₂, cytosolic c-PLA₂, lipoprotein-associated LpPLA₂, and calcium-independent iPLA₂ with inhibitors and substrates. We will also discuss new results on the precise nature and molecular dynamics of the interaction of these enzymes with specific substrate phospholipids pulled into the catalytic site from membranes and how new potent specific inhibitors block substrate phospholipid binding. Phospholipase A₂ is the initiator of eicosanoid formation in inflammatory processes, so it is a critical enzyme and inhibitors could provide new approaches to disease treatment.

Biography:

George Kokotos is the Chairman of the Department of   Chemistry   at the University of Athens, Greece. He studied chemistry at the University of Athens where he also obtained his P hD. He then conducted postdoctoral work in the Department of  Pharmaceutical  and Biological Chemistry at the University of London. He has   spent a sabbatical leave as a visiting Professor in the Department of Chemistry and Biochemistry at the University of California, San Diego. He has authored over 140 publications in peer-reviewed journals and edited two books on Bioactive Lipids and Lipases. He is also co-in ventor of more than 12 patents.

Abstract:

     Phospholipases A₂      (PLA₂) are enzymes that hydrolyze the sn-2 ester bond of the membrane phospholipids releasing free      fatty acids      and     lysophospholipids    .    Arachidonic acid    may be converted into  a variety of eicosanoids by v arious enzymes, while lysophosphatidylcholine into lysophosphatidic acid (LPA) by a secreted enzyme that exhibit   s l   ysophospholipase D activity known as autotaxin (ATX). Both enzymes are involved in the production of infla mmatory mediators and thus, constitute attractive targets for the development of novel agents for the treatment of   inflammatory diseases  . In addition, increased ATX expression and LPA production have been detected in a variety of cancers, which render s this enzyme a target for cancer treatment. A variety of small molecule PLA₂ inhibitors have been developed and some of them reached clinical trials. In the case of ATX, several inhibitors have been reported, however only limited studies using animal models are known. In our labs, we have developed several classes of novel PLA₂ inhibitors, including    2-oxoamide     s   and   thiazolyl   ketones targeting  GIVA cPLA₂, and fluoroketones targeting GVIA iPLA₂. We have recently shown that administration of   fluoroketone   FKGK18 to  non-obese  diabetic mice significantly re duced diabetes incidence in as sociation with improved glucose homeostasis, and β-cell preservation. In this presentation, we will discuss our most recent potent PLA₂ and ATX inhibitors. We will present two novel classes of highly potent inhibitors: 2-oxoesters for GIVA cPLA₂ and beta-lactones for GVIA iPLA₂. Such inhibitors were found to suppress the release of PGE₂ in renal mesangial cells. A lipidomic approach to monitor the effect of inhibitors will be discussed.

Biography:

Berit Johansen is professor of Biotechnology at Norwegian University of Science and Technology (NTNU), Norway; and gründer and CSO of Avexxin AS. She has a PhD in Molecular Genetics, obtained at NTNU. She has spent several periods as visiting scientist at international universities and companies, including: UCLA, Biogen Inc., University of Groningen, University of Uppsala and UCSD. Her scientific interests encompass unraveling cellular communication processes involving lipid signalling, with special emphasis on phospholipase A2 (PLA2) enzymes, including drug development targeting cPLA2. “Proof of concept” for topical treatment of psoriasis with a small molecule cPLA2 inhibitor has been achieved with. She received “Young scientist award” from European Federation of Biotechnology in 2003.           
 

Abstract:

    Eicosanoids,     the oxygenated met abolites of    arachidonic acid    (AA) compri se a large family of    bioactive lipids    that have diverse roles in regulating homeostatic processes, in modula ting inflammation and immune responses.    Phospholipase A2s    (PLA2s) are a group of enzymes that hydrolyze the sn-2 position of membrane phospholipids to relea se (typically unsaturated) fatty acids, including AA, and   ly   sophospholipids . Three major classes of PLA2s exist in the   mammalian system, including low molecular weight extracellular or secretory, sPLA2; high moleular weight calcium-independen, iPLA2; and  the group IVA calcium-dependent cytosolic PLA2, cPLA2α. The latter has received the most atte ntion because it is widely expressed in nearly all  mammalian cells  and due to its active participation in cell metabolism. cPLA2 is identified as the the rate-limiting provider of proinf lammatory mediators, including AA, and is thus an attractive target for the development of novel antiinflammatory agents. It is found that cPLA2α plays a major role in the chronic inflammation characterizing both psoriasis and rheumatoid arthritis. Novel inhibitors showing high potency and selectivity targeting cPLA2α are developed. These represent different chemistries, thus enabling various regimes for formulation, administration and tissue accumulation. Results will be presented to demonstrate mode of action for potent cPLA2α inhibitors in relevant cellular model systems for psoriasis and rheumatoid arthritis, efficacy in animal models of disease and “Proof of concept” for treatment of human disease.  

Biography:

Dr. Ramanadham was awarded his PhD from the Department of  Pharmacology  at Texas Tech University Health Sciences Center in 1985. He thesis project focused on cardiovascular  complications associated with diabetes. He has continued work in the diabetes area and is now engaged in studies to understand the contribution of  lipid singnaling to type 1 diabetes development. He has nearly 100 publications, serves on Journal Editorial Boards, and as a grant reviewer for both National and Intenational Diabetes Foundations. He is currently a Professor in the Department of Cell, Developmental, and Integrative Biology, and a Senior Scientist in the Comprehesive Diabetes Center at UAB. 

Abstract:

  Type 1 diabetes   (T1D) is a consequence of pancreatic islet b-cell destr uction, due to  apoptosis . Our lab is in vestigating underlying mechanisms that contribute to b-cell loss and we identified a prominent role for the group VIA Ca²⁺-independent   phosphoplipase   A₂b (iPLA₂b) in this process. The cytosolic iPLA₂b catalyzes   hydrolysis   of the sn-2 sbstituent from membrane   phopsholipids  . The islet b-cell membranes are enriched in arachidonate-containing phospholipids and activation of iPLA₂b in the b-cells leads to accumulations in   arachidonic acid   and its various oxidized metabolites (i.e. eicosanoids). The eicosanoids manifest different activities, some of which are proinflammatory and apoptotic and some are ant-inflammatory and anti-apoptotic. Inhibition, knockdown, or knockout of iPLA₂b significantly reduces   b-cell apopotosis   due to  ER stress  or proinflammatory cytokines. Further, d uring the development of autoimmune T1D, expression and activity of iPLA₂b increases and this is associated with generation of proinflammatory and  apoptotic lipid  signals. Consistent with this, we find that with selective inhibition of iPLA₂b in the spontaneously diabetes-prone non-obese diabetic (NOD) mouse, there is a significant reduction in islet infiltration by  leukocyte s, preservation of b-cell mass, and a dramatic amelioration of T1D. We further find that iPLA ₂b inhibition markedly reduces immune responses. These observations provide strong evidence for contribution of iPLA₂b-derived lipids to T1D development. Our on-going investigations reveal that activation of iPLA₂b triggers molecular mechanisms that favor generation of pro -apoptotic/pro-inflammatory signals and these work in concert to promote T1D development. Our work was supported by the American Diabetes Association, NIH/NIDDK, and the Iacocca Family Foundation.

Biography:

L. Ashley Cowart obtained her PhD in 2001 from Vanderbilt University and performed postdoctoral studies at the Medical University of South Carolina, where she is now associate professor in   Biochemistry  .  Dr. Cowart has participated heavily in developing the strong research programs in  lipid signaling  and lipidomics at MUSC. She has published over 40 manuscripts and authored numerous reviews in sphingolipid metabolism and signaling in diabetes.             
 

Abstract:

       Sphingosine-1-phosphate        is a       lysophospholipid       signaling molecule tha t works through both receptor dependent and independent mechanisms.  Sphingosine-1-phosphate is generated via       phosphorylation       of sphingosine by Sphingosine Kinases.  We discovered that Sphingosine Kinase 1 is upregulated by saturated      fatty acids     , a finding which placed this pathway in the context of metabolic     homeostasis    .  Since those initial studies, our group and ot  hers have demonstrated roles for Sphingosine Kinase 1 in     pathophysiological     processes in numerous organs including pancreas,    skeletal muscle   , adipose tissue, and liver.  Moreover, ablation of this pathway in mice co nferred resistance to obesity-induced inflammation and    insulin    resistance.  Together, these data have  supported the general idea that Sphingosine Kinase 1 mediates   obesity-induced   disease. To gain more mechanistic insights, we recently gener ated mice with an adipocyte-specific sphingosine kinase 1 deletion.  Data from these animals has revealed novel and surprising roles for this pathway in maintaining metabolic   homeostasis  .  For example, in contrast to the whole-body deletion, which exhibits protection from obesity-induced  insulin  resistance,  the adipocyte-specific sphingosine kinase 1 deletion mouse exhibits basal insulin resistance.  These and other data h  ave revealed that this pathway serves both protective and deleterious roles depending on cell type and disease context. Ongoing work in the laboratory is addressing the specific roles for  sphingosine-1-phosphate  signaling in regulating crucial adipocyte functions including lipogenesis, lipolysis, proliferation, and differentiation. These pathways might eventually be pharmacologically targeted for treatment of obesity and/or obesity-induced disease. 

Biography:

Charles Chalfant received his PhD from the University of South Florida-College of   Medicine   and was an NRSA postdoctoral fellow at both Duke Medical Center and The Medical University of South Carolina under Dr. Yusuf hannun.. He is currently a GS15 Research Career Scientist w ith the Richmond VAMC. He is also a tenured Professor and Vice Chair of the Department of  Biochemistry  & Molecular Biology at Virginia Commonwealth University (VCU)-School of Medicine. He is c  urrently holds the Paul M. Corman, M.D. Endowed Chair in Cancer Research for the VCU Massey Cancer Center and has published >100 papers in reputed journals. 

Abstract:

New roles for    sphingolipids    such as ceramide,   ceramide-1-phosphate   (C1P), and sphingosine-1-p hosphate continue to emerge. My research, for example, has implicated C1P as a major regulator of   eicosanoid   synthesis, and despite the importance of eicosanoids in the inflammatory process, the regulation of eicosanoid synthesis proximal to the activation of Group IVA   phospholipase A₂   (cPLA₂a) is still an enigma. In this regard, my laboratory demonstrated that C1P is a direct and required lipid co-factor for cPLA₂a activation in cellular models. In further studies, the interaction site for C1P was localized to the calcium-lipid binding domain (C2 domain) of the enzyme allowing for the genetic ablation of the site in vivo via the generation of a cPLA₂a knock-in (KI) mouse. In this lecture, the characterization of this new mouse model in comparison to the full genetic ablation of the enzyme will be presented. Specifically, the loss of the C1P/cPLA₂a interaction induced a “class-switch” in the production specific   eicosanoids   and specialized  lipid mediators  driving both sepsis resistance and accelerated wound repair. In further mech anistic studies, C1P was found to modulate the substrate specificity of cPLA₂a explaining the “class switch” as to bioactive lipid mediators observed in the cPLA₂a KI mouse.  Overall, these observations led to two new findings: 1) C1P is a pro-inflammatory signaling molecule that directs cPLA₂a in the utilization of primarily  phospholipids  with sn-2 arachidonic acid while simultaneously blocking the utilization  of phospholipids with sn-2 docosahexaenoic acid; and 2) cPLA₂a has previously overlooked functions in the resolution of inflammation and immune responses.

Biography:

Christoforos G. Kokotos is an Assistant Professor of Organic Chemistry at the Department of Chemistry at the National and Kapodistrian University of Athens, Greece. He studied chemistry at the University of Athens and he moved to the University of Bristol, UK to obtain his Ph.D. He then conducted postdoctoral work in the Department of Chemistry of Princeton University, USA. He has authored over 45 publications in peer-reviewed journals and has been selected in prestigious rising star events of organic chemistry including EuCheMS Young Investigators Workshop 2014, 9^th Young Academic Investigators Award, 248^th ACS Meeting 2014 and Burgenstock Conference 2016.

Abstract:

2-Hydroxy      fatty acids      are important components of a  subset of mammalian     sphingolipids    . Current evidence cl e arly shows that 2-hydroxy ceramides and 2-hydroxy complex sphingolipids have unique functions in membrane     homeostasis     and    cell signaling   . T he biosynthesis of   2-hydroxy fatty acids   is accomplished by  the enzyme fatty acid 2-  hydroxylase (FA2H), which stereospecifically produces the    ( R)-enantiomers   . On the other hand, 2-hydroxy oleic acid has been identified as a potent antitumor compound (Minerval) acting against cancer by inducing cell cycle arrest, followed by  apoptosis in   human leukemia   cells or diff erentiation and   autophagy   in the case of human glioma cells. In 2011, the European Med icines Agency designated  2-hydroxy oleic acid  as an   orphan medicinal product for the treatment of   glioma  . We have been pre viously involved in the asymmetric  organocatalytic  α-functionalization of carbonyl co mpounds. In this presentation, we will discuss our most recent application of these methodologies, as well as the development of novel synthetic approaches for the synthesis of enantioenriched α-substituted fatty acids. We will present the successful application of this methodology in the α-functionalization of   fatty acids   with hydroxyl, fluoro and sulfenyl moieties. Having in hand a methodology for the fast assembly of chiral and racemic α-functionalized  fatty acids , their properties as enzyme inhibitors and signaling-molecules will be pursued. In addition, organocatalytic methodologies for the synthesis of phospholipase A  ₂ inhibitors will be presented.

Biography:

Suzanne E. Barbour has a BS (Chemistry) from Rutgers University, a PhD (Molecular Biology and Genetics) from The Johns Hopkins University, and postdoctoral training from the University of California San Diego. From 1993-2015, Suzanne was on the faculty at the Virginia Commonwealth University School of Medicine. In 2013, she became a Program Director in the Molecular and Cellular Biosciences at the National Science Foundation where she ran a program in cellular dynamics and function. Suzanne moved to the University of Georgia in July 2015 where she is Dean of the Graduate School and Professor of Biochemistry & Molecular Biology.
 

Abstract:

The Group VIA     phospholipase A₂     (iPLA₂b) is highly expressed in metabolically active tissues and recent studies have connected the enzyme to a variety of metabolic diseases. Our studies are focused on the role of the enzyme in fatty liver disease. Exogenous     unsaturated fatty acids     (UFA) suppress expression and processing of sterol regulatory element    binding protein-1    (SREBP-1), a transcri ption factor that regulates lipogenic gene expression in the liver. We compared hepatic   lipid metabolism   in iPLA  ₂b^-/- and wild type mice, to test the hypothesis that the iPLA₂b might be a source of endogenous UFA that regulate SREBP-1 and thereby modulate fatty liver. As expected, iPLA₂b^-/- livers contained more SREBP-1c and exhibited increased processing of this    protein   , compared to wild typ e livers. The changes in SREBP-1 expression/ processing correlated with increased   lipogenic   gene expression, synthesis of  fatty acids  and triacylglycerols (TAG), and TAG mas   s in iPLA ₂b^-/- livers. We also observed evidence of reduced secretion of TAG, cholesterol, and cholesterol ester in iPLA₂b^-/- hepatocytes, suggesting that TAG accumulation in iPLA₂b^-/- livers is the result of both increased synthesis and reduced secretion. Our studies indicate that iPLA₂b-derived lipids contribute to pathogenesis of at least two metabolic diseases. Identification of the bioactive lipids and their mechanisms of action may uncover novel ways to treat diabetes mellitus and fatty liver disease.