Download or read book Metabolic Regulation by Lipid Activated Receptors written by Maxwell A. Ruby and published by . This book was released on 2010 with total page 214 pages. Available in PDF, EPUB and Kindle. Book excerpt: Obesity and related metabolic disorders have reached epidemic levels with dire public health consequences. Efforts to stem the tide focus on behavioral and pharmacological interventions. Several hypolipidemic pharmaceutical agents target endogenous lipid receptors, including the peroxisomal proliferator activated receptor alpha (PPAR alpha) and cannabinoid receptor 1 (CB1). To further the understanding of these clinically relevant receptors, we elucidated the biochemical basis of PPAR alpha activation by lipoprotein lipolysis products and the metabolic and transcriptional responses to elevated endocannabinoid signaling. PPAR alpha is activated by fatty acids and their derivatives in vitro. While several specific pathways have been implicated in the generation of PPAR alpha ligands, we focused on lipoprotein lipase mediated lipolysis of triglyceride rich lipoproteins. Fatty acids activated PPAR alpha similarly to VLDL lipolytic products. Unbound fatty acid concentration determined the extent of PPAR alpha activation. Lipolysis of VLDL, but not physiological unbound fatty acid concentrations, created the fatty acid uptake necessary to stimulate PPAR alpha. Consistent with a role for vascular lipases in the activation of PPAR alpha, administration of a lipase inhibitor (p-407) prevented PPAR alpha dependent induction of target genes in fasted mice. Apolipoprotein CIII, an endogenous inhibitor of lipoprotein lipase, regulated access to the lipoprotein pool of PPAR alpha ligands. Our results support a role for the local generation of PPAR alpha ligands by lipase activity. The endocannabinoid system regulates diverse physiological functions, including energy balance. While loss of CB1 signaling has more pronounced effects on lipid parameters than expected based on weight loss alone, direct demonstration of endocannabinoid regulation of lipid metabolism is lacking. To test the effects of endogenously produced cannabinoids on lipid metabolism, independent of alterations in food intake, we analyzed tissues from mice treated with IDFP, an organophosphorus inhibitor of endocannabinoid breakdown. IDFP administration inhibited hepatic monoacylglycerol lipase leading to elevated levels of 2-arachidonylglycerol. We found that IDFP administration caused accumulation of apoE depleted VLDL. HDL particles accumulated apoE and failed to transfer it to VLDL in vitro. Importantly, these effects were prevented by pharmacological inhibition of CB1 and absent in plasma from CB1 mice. IDFP also caused a CB1-dependent increase in hepatic triglycerides. Thus, endocannabinoids inhibit the transfer of apoE from HDL to VLDL leading to apoE depletion of triglyceride rich lipoproteins. Microarray analysis allowed us to determine the effects of IDFP on expression of genes involved in lipid metabolism and to discover novel cannabinoid responsive genes. IDFP increased expression of lipogenic and SREBP2 target genes in a CB1-dependent fashion. On a global scale, pre-administration of a CB1 antagonist prevented many of the IDFP induced alterations in gene expression. IDFP decreased expression of genes involved in amino acid metabolism and inflammation. PCR analysis of selected mRNAs confirmed several of the key array findings. Our work indicates that endocannabinoids exert a large influence on hepatic lipid metabolism independent of food intake and suggest that peripherally restricted CB1 antagonists may be of therapeutic value. Overall, these findings shed light on the endogenous mechanisms of PPAR alpha activation and the hepatic responses to Cb1 activation. This information may help guide the continuing effort to develop treatments for metabolic disease.
Download or read book Innovative Medicine written by Kazuwa Nakao and published by Springer. This book was released on 2015-10-13 with total page 330 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is devoted to innovative medicine, comprising the proceedings of the Uehara Memorial Foundation Symposium 2014. It remains extremely rare for the findings of basic research to be developed into clinical applications, and it takes a long time for the process to be achieved. The task of advancing the development of basic research into clinical reality lies with translational science, yet the field seems to struggle to find a way to move forward. To create innovative medical technology, many steps need to be taken: development and analysis of optimal animal models of human diseases, elucidation of genomic and epidemiological data, and establishment of “proof of concept”. There is also considerable demand for progress in drug research, new surgical procedures, and new clinical devices and equipment. While the original research target may be rare diseases, it is also important to apply those findings more broadly to common diseases. The book covers a wide range of topics and is organized into three complementary parts. The first part is basic research for innovative medicine, the second is translational research for innovative medicine, and the third is new technology for innovative medicine. This book helps to understand innovative medicine and to make progress in its realization.
Download or read book Lipid Signaling and Metabolism written by James M. Ntambi and published by Academic Press. This book was released on 2020-08-09 with total page 570 pages. Available in PDF, EPUB and Kindle. Book excerpt: Lipid Signaling and Metabolism provides foundational knowledge and methods to examine lipid metabolism and bioactive lipid signaling mediators that regulate a broad spectrum of biological processes and disease states. Here, world-renowned investigators offer a basic examination of general lipid, metabolism, intracellular lipid storage and utilization that is followed by an in-depth discussion of lipid signaling and metabolism across disease areas, including obesity, diabetes, fatty liver disease, inflammation, cancer, cardiovascular disease and mood-related disorders. Throughout, authors demonstrate how expanding our understanding of lipid mediators in metabolism and signaling enables opportunities for novel therapeutics. Emphasis is placed on bioactive lipid metabolism and research that has been impacted by new technologies and their new potential to transform precision medicine. - Provides a clear, up-to-date understanding of lipid signaling and metabolism and the impact of recent technologies critical to advancing new studies - Empowers researchers to examine bioactive lipid signaling and metabolism, supporting translation to clinical care and precision medicine - Discusses the role of lipid signaling and metabolism in obesity, diabetes, fatty liver disease, inflammation, cancer, cardiovascular disease and mood-related disorders, among others
Download or read book Regulation of Lipid Metabolism and Adipogenesis by the PPAR and LXR Families of Nuclear Receptors written by Sarah Rebecca Hummasti and published by . This book was released on 2006 with total page 230 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Lipid Activated Nuclear Receptors written by Matthew C. Gage and published by Humana Press. This book was released on 2019-04-01 with total page 220 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book covers a wide range of state-of-the-art methodologies and detailed protocols currently used to study the actions that lipid-activated nuclear receptors and their co-regulators have in tissues and immune cell types considered classic metabolic “powerhouses”. This includes the liver, adipose tissue, and monocytes/macrophages present in these and other metabolic tissues. While the main focus is on the oxysterol receptor or Liver X Receptor (LXR), the majority of the methods described can be easily applied to multiple nuclear receptors, as well as to other tissues or cell types. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Lipid-Activated Nuclear Receptors: Methods and Protocols serves as an ideal guide for researchers pursuing the vital study of nuclear receptor biology and beyond.
Download or read book Role of Branched Chain Fatty Acids on Gene Regulation of Lipid Metabolism Via Fatty Acid Binding Proteins and Peroxisome Proliferator Activated Receptors written by Thorsten Hanhoff and published by . This book was released on 2004 with total page 260 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book PPARs in Cellular and Whole Body Energy Metabolism written by Walter Wahli and published by MDPI. This book was released on 2019-01-09 with total page 583 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is a printed edition of the Special Issue "PPARs in Cellular and Whole Body Energy Metabolism" that was published in IJMS
Download or read book Metabolic Regulation written by Keith N. Frayn and published by John Wiley & Sons. This book was released on 2009-02-11 with total page 352 pages. Available in PDF, EPUB and Kindle. Book excerpt: Metabolic Regulation looks in detail at how molecules, cells and tissues operate collectively in human health and disease, using an approach that has become known as ‘integrative physiology’. Since the publication of the first edition of this extremely well received book, the understanding of how metabolism is regulated has developed substantially in several ways, for example with the discovery of the hormone leptin, and also in the continuing advances in the understanding of gene expression. Full details of these and other new advances are included in this fully updated edition. Carefully laid out with relevant and clearly explained examples, and containing much new material, this new edition covers in an integrated way: concepts and mechanisms, digestion and intestinal absorption, organs and tissues, endocrine organs and hormones, the integration of carbohydrate, fat and protein metabolism, the nervous system and metabolism, lipoprotein metabolism, diabetes mellitus, energy balance and body weight regulation and how the body copes with some extreme situations. The author, Keith Frayn, who has many years’ experience teaching and researching in this subject, has written a book of great clarity, which is an extremely valuable tool for scientists, practitioners and students working and studying across a broad range of allied health sciences including nutrition, dietetics, sports science and nursing. Students of medicine, physiology, biochemistry and biological sciences will also find much of great use and interest in this book. All libraries in research establishments, universities and medical schools where these subjects are studied and taught should have multiple copies of this excellent book on their shelves. Keith Frayn is Professor of Human Metabolism at the University of Oxford, UK.Reviews of the First Edition ‘This is an excellent textbook’: Trends in Endocrinology and Metabolism ‘The coverage is excellent for students following courses such as nutrition and human biology’:Biologist ‘This book is ideal for medical students’:Australian Society for Biochemistry and Molecular Biology
Download or read book Syndrome X written by Terry Kirsten Strom and published by Simon and Schuster. This book was released on 2002-02-28 with total page 292 pages. Available in PDF, EPUB and Kindle. Book excerpt: Millions of Americans follow the "best" medical advice every day to prevent heart attacks -- eating the standard low-fat, high-carbohydrate diet so widely recommended by doctors -- but in fact they are placing themselves at greater risk for heart disease. In Syndrome X: Overcoming the Silent Killer That Can Give You a Heart Attack, Dr. Gerald Reaven, the world-renowned physician who identified and named this silent killer, explains why the standard heart-healthy diet can be dangerous and lays out a simple six-step program to reduce the risk of heart disease for everyone. The problem stems from a little-known cluster of metabolic abnormalities known as Syndrome X. The insulin resistance that lies at the heart of the syndrome can turn normal rules of good health upside down and dramatically increase the risk of heart disease. Fortunately, Syndrome X can be cured. This important book explains how to identify the disorder and provides a program of diet and exercise (plus medication when necessary) that can render Syndrome X harmless. Tested in carefully controlled research settings and in practice, this remarkable new approach has the ability to reduce the risk of heart attacks and heart disease for all of us. Dr. Reaven shows how eating a diet relatively high in "good" fats (40 percent of calories) can dramatically lower the risk of heart disease if you have Syndrome X. The approach seems paradoxical: Everyone "knows" that fat is bad, so how can more fat possibly lead to better health? The answer lies in the type of fat and the body chemistry of the people who consume it. If you have the abnormal metabolism called Syndrome X, eating a low-fat, high-carbohydrate diet to lower your LDL and blood fats won't protect you. In fact, doing so will increase the odds of heart disease. Millions of Americans have the potentially deadly, yet easily identifiable signs of Syndrome X -- but few cases are detected in time, because most physicians don't know what to look for. This trailblazing book will change that, making doctors and patients aware of the problem -- and its easy solution, an integrated program of diet and exercise that simultaneously reduces all the risk factors for heart disease, including Syndrome X. Dr. Reaven's discovery of Syndrome X has shown us that the standard approach to preventing heart disease is dangerous for many of us. Now, his safe, proven new approach explains how millions can drastically reduce their risk of heart disease. His program works not only for those who have Syndrome X, but also for anyone who simply wants to reduce the risk of heart disease.
Download or read book Metabolic Regulation by Nuclear Receptor FXR and Micro RNA 34a in Health and Disease written by and published by . This book was released on 2014 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book The Heterogeneity of Cancer Metabolism written by Anne Le and published by Springer. This book was released on 2018-06-26 with total page 186 pages. Available in PDF, EPUB and Kindle. Book excerpt: Genetic alterations in cancer, in addition to being the fundamental drivers of tumorigenesis, can give rise to a variety of metabolic adaptations that allow cancer cells to survive and proliferate in diverse tumor microenvironments. This metabolic flexibility is different from normal cellular metabolic processes and leads to heterogeneity in cancer metabolism within the same cancer type or even within the same tumor. In this book, we delve into the complexity and diversity of cancer metabolism, and highlight how understanding the heterogeneity of cancer metabolism is fundamental to the development of effective metabolism-based therapeutic strategies. Deciphering how cancer cells utilize various nutrient resources will enable clinicians and researchers to pair specific chemotherapeutic agents with patients who are most likely to respond with positive outcomes, allowing for more cost-effective and personalized cancer therapeutic strategies.
Download or read book Prokaryotic Metabolism and Physiology written by Byung Hong Kim and published by Cambridge University Press. This book was released on 2019-05-16 with total page 509 pages. Available in PDF, EPUB and Kindle. Book excerpt: Extensive and up-to-date review of key metabolic processes in bacteria and archaea and how metabolism is regulated under various conditions.
Download or read book Fat Detection written by Jean-Pierre Montmayeur and published by CRC Press. This book was released on 2009-09-14 with total page 646 pages. Available in PDF, EPUB and Kindle. Book excerpt: Presents the State-of-the-Art in Fat Taste TransductionA bite of cheese, a few potato chips, a delectable piece of bacon - a small taste of high-fat foods often draws you back for more. But why are fatty foods so appealing? Why do we crave them? Fat Detection: Taste, Texture, and Post Ingestive Effects covers the many factors responsible for the se
Download or read book Lipids and Insulin Resistance written by Iwar Klimes and published by . This book was released on 2002 with total page 608 pages. Available in PDF, EPUB and Kindle. Book excerpt: Insulin resistance is central to the development of a cluster of prevalent conditions including Type 2 diabetes, dyslipidemias, hypertension and cardiovascular disease. Scientists' current understanding of the etiology of insulin resistance is limited and few therapies are available. However, it is clear that the understanding of lipid metabolism and of lipids in their many forms and functions provides the keys to unlocking the mysteries of insulin resistance. In this volume, an international group of investigators from a range of lipid-related disciplines explores new ideas for therapeutic targets.
Download or read book The Farnesoid x activated Receptor and Its Role in Lipid Metabolism written by Heidi Rachelle Kast and published by . This book was released on 2001 with total page 466 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Food Proteins and Peptides Emerging Biofunctions Food and Biomaterial Applications written by Chibuike C. Udenigwe and published by Royal Society of Chemistry. This book was released on 2021-06-09 with total page 537 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book discusses the chemistry of food proteins and peptides and their relationship with nutritional, functional, and health applications. Bringing together authorities in the field, it provides a comprehensive discussion focused on fundamental chemistries and mechanisms underpinning the structure-function relationships of food proteins and peptides. The functional and bioactive properties hinge on their structural features such as amino acid sequence, molecular size, hydrophobicity, hydrophilicity, and net charges. The book includes coverage of advances in the nutritional and health applications of protein and peptide modifications; novel applications of food proteins and peptides in the development of edible functional biomaterials; advances in the use of proteomics and peptidomics for food proteins and peptide analysis (foodomics); and the relevance of food protein and peptide chemistries in policy and regulation. Research into the fundamental chemistries behind the functional, health and nutritional benefits is burgeoning and has gained the interest of scientists, the industry, regulatory agencies, and consumers. This book fills the knowledge gap providing an excellent source of information for researchers, instructors, students, food and nutrition industry, and policy makers.
Download or read book Regulation of Lipid Homeostasis Inflammatory Signalling and Atherosclerosis by the Peroxisome Proliferator activated Receptor Delta written by Lazar A. Bojic and published by . This book was released on 2013 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: The peroxisome proliferator-activated receptor (PPAR) is a ligand-dependent transcription factor that has been implicated in metabolic and inflammatory regulation. The molecular and physiological mechanisms by which PPAR activation regulates lipid metabolism, inflammatory signaling and protection from atherosclerosis in states of metabolic disturbance such as insulin resistance and dyslipidemia, were investigated in a series of in vitro and in vivo studies. In vitro experiments demonstrated that PPAR activation inhibits atherogenic lipoprotein-induced lipid accumulation and the associated proinflammatory responses. The primary mechanisms for these effects were increased fatty acid -oxidation, decreased lipoprotein lipase (LPL) activity, reduced MAPK signaling and improved insulin signaling. With regard to cholesteryl ester (CE)-rich low-density lipoprotein (LDL), the PPAR activators stimulated cholesterol efflux via ABCA1 to apoAI, resulting in the inhibition of native and modified LDL-induced CE accumulation. In vivo studies were conducted in high fat, high cholesterol (HFHC)-fed low-density lipoprotein receptor null (Ldlr-/- ) mice. Following a 4-week induction phase of HFHC-feeding to stimulate early atherosclerotic lesion development, dietary supplementation with GW1516 for a subsequent 8-weeks prevented further plaque progression. This prevention was linked to inhibition of dyslipidemia, hyperinsulinemia, and glucose and insulin intolerance. Furthermore, GW1516 strongly attenuated aortic inflammation, insulin resistance and endoplasmic reticulum (ER)-stress, which likely contributed to inhibition of lesion progression. Additional studies in the liver showed that PPAR activation inhibits hepatic TG accumulation induced by HFHC-feeding. To further probe the mechanism for this effect, experiments were conducted in primary mouse hepatocytes isolated from wild-type (WT) or adenosine monophosphate-activated protein kinase (AMPK) 1-/- mice. These studies revealed that PPAR activation in the liver stimulates fat oxidation due to upregulation of the PPAR-target gene carnitine palmitoyl transferase (Cpt) 1a, which was independent of AMPK activation. Furthermore, GW1516 inhibited de novo lipogenesis, which was partially dependent on AMPK activation. The residual inhibitory effect on fatty acid synthesis was associated with correction of selective hepatic insulin resistance. In summary, these studies provide significant insight and support for PPAR activation as a therapeutic strategy to treat the dysregulation of lipid homeostasis, inflammatory signaling, metabolic disease, and their cardiovascular complications.
