Download or read book Hepatic De Novo Lipogenesis and Regulation of Metabolism written by James M. Ntambi and published by Springer. This book was released on 2015-12-17 with total page 309 pages. Available in PDF, EPUB and Kindle. Book excerpt: The liver is the largest solid vital organ in mammals that supports other organ in the body in some facet. This book synthesizes all the primary and relevant metabolic information that one needs to review to understand the complex and diverse role of the liver in metabolism. With the current epidemic of metabolic diseases, it is of immediate importance to understand the contribution of the liver in health and its role in the development of impaired metabolic regulation. This book covers the many studies that have unmasked important roles that proteins expressed in the liver play in the development of or protection from metabolic diseases. One of the major metabolic functions of the liver is to carry out de novo lipogenesis, which is the metabolic pathway that allows the conversion of excess carbohydrates into fatty acids. The process of de novo lipogenesis is covered in depth within this volume. The book is an important contribution to the vast literature and ongoing research on liver function.

Download or read book Circadian Integration of Hepatic de Novo Lipogenesis and Peripheral Energy Substrates Utilization written by Sihao Liu and published by . This book was released on 2012 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: The liver maintains energy substrate homeostasis by synchronizing circadian or diurnal expression of metabolic genes with the feeding/fasting state. The activities of hepatic de novo lipogenic gene products peak during feeding, converting carbohydrates into fats that provide vital energy sources for peripheral tissues. Conversely, deregulated hepatic lipid synthesis leads to systemic metabolic dysfunction, establishing the importance of temporal regulation of fat synthesis/usage in metabolic homeostasis. Pharmacological activation of peroxisome proliferator-activated receptor [delta]/[beta] (PPAR[delta]/[beta]) improves glucose handling and systemic insulin sensitivity. However, the mechanisms of hepatic PPAR[delta] actions and the molecular pathways through which it is able to modulate global metabolic homeostasis remain unclear. Here we show that hepatic PPAR[delta] controls the diurnal expression of lipogenic genes in the dark/feeding cycle. Adenovirus mediated liver restricted activation of PPAR[delta] promotes glucose utilization in the liver and fat utilization in the muscle. Liver specific deletion of either PPAR[delta] or the PPAR[delta]-regulated lipogenic gene acetyl-CoA carboxylase 1 (ACC1) reduces muscle fatty acid uptake. Unbiased metabolite profiling identifies 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine (SOPC) as a serum lipid derived from the hepatic PPAR[delta]-ACC1 activity that reduces postprandial lipid levels and increases muscle fatty acid uptake. These findings reveal a regulatory mechanism that coordinates lipid synthesis and utilization in the liver-muscle axis, providing mechanistic insights into the hepatic regulation of systemic energy substrates homeostasis.

Download or read book Role of Monounsaturated Fatty Acids in Metabolic Regulation written by and published by . This book was released on 2013 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The global epidemic of overweight and obesity is alarming because these conditions increase the risk for the development of other chronic metabolic disorders, including nonalcoholic fatty liver disease and insulin resistance, among others. Thus, it is increasingly important to understand factors that influence disease vulnerability caused by increased adiposity and how such factors exert their effects. High-fat diets (HFD) and high-carbohydrate diets (HCD) promote obesity by contributing fatty acids directly (HFD) or indirectly (HCD) that accumulate in adipose tissue depots. Fatty acids are synthesized from carbohydrates via the de novo lipogenesis (DNL) pathway. The stearoyl-CoA desaturase (SCD) family of enzymes plays a key role in DNL, desaturating both dietary and de novo synthesized saturated fatty acids to yield monounsaturated fatty acids (MUFA), primarily palmitoleate and oleate. Several studies have demonstrated that the SCD1 isoform exerts significant control over susceptibility to diet-induced metabolic disorders. The overall aim of the present work was to increase our understanding of the role of SCD and the products of the reaction this enzyme catalyzes on mediating the unfavorable metabolic effects of HCD and HFD. Our results demonstrate that hepatic de novo synthesized oleate is more potent than hepatic palmitoleate in promoting increased body weight, adiposity and hepatic lipid accumulation. We also demonstrate that endogenous, hepatic oleate is strongly associated with rates of DNL and fatty acid oxidation in white adipose tissue, suggesting that it also acts in an extrahepatic manner. In addition, our studies reveal that dietary and endogenously synthesized oleate prevents HCD-induced inflammation and endoplasmic reticulum (ER) stress. Our results also suggest that the transcriptional coactivator PGC-1ơ may be involved in mediating the hepatic ER stress response that develops when hepatic oleate levels are restricted. In a separate study, we reveal that the secreted protein Lipocalin 2 (Lcn2), which has been proposed to exert protective effects against the detrimental consequences of a HFD, does not mediate the hypermetabolism and associated resistance to HFD-induced obesity in skin-specific SCD1 knockout mice. Overall, this body of work contributes to our understanding of the role of SCD and MUFA in regulation of lipid metabolism and diet-induced metabolic disorders.

Download or read book Effects of Weight Altering Peptides on de Novo Lipogenesis and Hepatic Carbohydrate Metabolism in Mice written by Scott Middleton Turner and published by . This book was released on 2002 with total page 304 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Novel Roles of GLP 1 and GLP 2 in the Regulation of Hepatic Lipid Lipoprotein Homeostasis and the Involvement of BAT Activation written by Jennifer Taher and published by . This book was released on 2017 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Major complications of insulin resistance and type 2 diabetes (T2D) include the development of non-alcoholic fatty liver disease (NAFLD) and an atherogenic fasting dyslipidemic profile, primarily due to increases in hepatic very low density lipoprotein (VLDL) production. Recent studies have implicated neuronal signalling in the control of hepatic lipid metabolism and VLDL production. The gut derived hormones glucagon-like peptide (GLP)-1 and GLP-2 have been shown to signal through neuronal pathways and display postprandial hypolipidemic and hyperlipidemic actions respectively. Furthermore, activation of brown adipose tissue (BAT) through the sympathetic nervous system also displays hypolipidemic actions and has recently been shown to be activated by GLP-1. We hypothesized that GLP-1 and GLP-2 will play opposing roles by decreasing and increasing VLDL production and NAFLD respectively. We further hypothesized that the effects of GLP-1 in modulating lipid metabolism occur through the activation of BAT. Using the Syrian Golden hamster, we showed that the GLP-1 receptor (GLP-1R) agonist exendin-4 decreased body weight, fasting dyslipidemia and VLDL overproduction by enhancing lipid utilization and decreasing hepatic de novo lipogenesis. These effects occurred through a vagal signalling pathway and were independent of changes in food consumption. To assess the involvement of BAT in the hypolipidemic actions of GLP-1, we first characterized the hamster as a novel and effective model of BAT activation. Î ̨3-adrenergic receptor (Î ̨3-AR) agonism activated hamster BAT, induced browning of WAT and prevented diet-induced NAFLD. The hypolipidemic actions of GLP-1R agonism were partially mediated by BAT as shown in hamsters that underwent BAT removal. Conversely, the sister peptide GLP-2 increased VLDL production and hepatic steatosis in hamsters and mice. Interestingly, GLP-2R knockout (KO) mice were protected against diet-induced dyslipidemia but displayed enhanced hepatic lipid accumulation. An observed reduction in VLDL-TG levels indicated that the enhanced hepatic lipid levels may be due to decreased VLDL production. Taken together, this thesis demonstrates that GLPs play critical but opposing roles in regulating hepatic lipid accumulation and VLDL production. Modulating the balance of GLPs in vivo may be a potential therapeutic approach to correct the dyslipidemia and NAFLD commonly associated with the metabolic syndrome.

Download or read book The CREBH in Hepatic Lipid and Lipoprotein Metabolism written by Miaoyun Zhao and published by . This book was released on 2014 with total page 67 pages. Available in PDF, EPUB and Kindle. Book excerpt: Hyperlipidemia is reemerging as an important cardiovascular disease risk factor and other metabolic disorders, such as obesity, insulin resistance and type-2 diabetes. Hepatic de novo lipogenesis is controlled by a family of the b-zip transcription factors, the sterol regulatory element-binding proteins (SREBPs), which targets downstream genes involved in free fatty acids, triglycerides and cholesterol synthesis. Regulation of SREBPs signaling is controlled by a cluster of the ER membrane-bound proteins, the insulin induced gene-1(Insig-1) and gene-2 (Insig-2) and the SCAP protein. The cAMP responsive element binding protein H (CREBH) is a recently identified member of this family. CREBH is selectively and highly expressed in the liver and small intestine which is actively involved in lipid and glucose metabolism. However, its underlying molecular mechanisms are not fully understood. Here we demonstrated CREBH inhibits hepatic lipid de novo synthesis through modulating the expression of insulin induced gene-2 (Insig-2) isoform-a, a liver specific isoform of Insig-2, which is involved in the activation of sterol regulatory element-binding proteins (SREBPs). Metabolic cues, such as fasting, glucagon and cAMP agonist, activated CREBH which in turn inhibited SREBP-1c and SREBP-2 activation via upregulate the abundance of Insig-2a in hepatocytes. Depletion or suppression of CREBH expression by refeeding inhibited Insig-2a expression, which in turn hyperactivated SREBP-1c and -2, leading to the activation of hepatic de novo lipid synthesis, accumulation of lipids in hepatocytes and systemic hyperlipidemia. We further demonstrated that depletion of CREBH reduced both mRNA and protein expression of apolipoprotein B (apoB). In vitro, transient expression of CREBH cDNAs in McA cells induced significant increase of apoB mRNA and protein expression, which indicated the positive regulatory impact of CREBH on apoB biosynthesis. This study establishes the CREBH-Insig-2a as a novel metabolic pathway that regulates hepatic de novo lipogenesis. This novel finding provides new mechanistic insight into the pathogenesis of hyperlipidemia in metabolic diseases.

Download or read book Regulation of Hepatic Metabolism written by Frank Lundquist and published by . This book was released on 1974 with total page 858 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Regulation of Hepatic Metabolism written by K. Jungermann and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 495 pages. Available in PDF, EPUB and Kindle. Book excerpt: The liver is an exceptionally complex and diverse organ that functions both as an exocrine and an endocrine gland. It secretes bile, which contains many con stituents in addition to bile salts, and it synthesizes and releases many substances in response to the body's demands, including prohormones, albumin, clotting factors, glucose, fatty acids, and various lipoproteins. It has a dual blood supply providing a rich mixture of nutrients and other absorbed substances via the portal vein and oxygen-rich blood via the hepatic artery. This functional heterogeneity is accompanied by cellular heterogeneity. The liver contains many cell types including hepatic parachymal cells, Kiipffer cells, Ito cells, and endothelial cells. The most abundant cell type, the parenchymal cells, are biochemically and structurally heterogeneous. The cells in the oxygen-rich areas of the portal triad appear more dependent on oxidative metabolism, whereas those around the central vein (pericentral, perivenous, or centrolobular areas) are more dependent upon an anaerobic mechanism. Throughout this volume the latter three terms are used synonymously by various authors to indicate the five to eight layers of cells radiating from the central vein. Structural and metabolic heterogeneity of hepatic parenchymal cells has been demonstrated by a variety of approaches, including histochemical, ultra structural, and ultramicrobiochemical studies. This microheterogeneity is linked to the physiological functions of the liver and its response to injurious substances.

Download or read book The Role of Hepatic Stearoyl CoA Desaturase 1 in Regulating Systemic Metabolism written by Ahmed Mobarak Aljohani and published by . This book was released on 2017 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Increased prevalence of overweight and obesity represents a public health crisis, making people more susceptible for chronic metabolic diseases such as type 2 diabetes and non-alcoholic fatty liver disease. Increased consumption of carbohydrate promotes de novo lipogenesis and increases fat accumulation in adipose tissues. Stearoyl-CoA desaturase 1 (SCD1) is a critical regulator of lipogenesis, desaturating saturated fatty acids (SFA), mainly palmitate and stearate, into monounsaturated fatty acids (MUFA), palmitoleate and oleate, respectively. Studies using SCD1 deficient mouse models demonstrated a significant reduction of hepatic de novo lipogenesis, decreased body weight, enhanced glucose utilization in peripheral tissues and increased insulin sensitivity. The overall aim of the present work was to provide more insight into the contribution of liver derived MUFA in regulating systemic glucose metabolism. Our results reveal that hepatic SCD1 deficiency enhances glucose utilization in the liver and adipose tissue through upregulated GLUT1 and GLUT4, respectively. Increased glucose uptake correlated with induced hepatic expression and plasma levels of fibroblast growth factor 21 (FGF21). Feeding triolein, but not tristearin, supplemented HCD diet reduces elevated plasma FGF21 and restores blood glucose levels, suggesting that hepatic oleate regulates systemic glucose metabolism either directly or through modulating hepatic FGF21. In addition, our findings indicate that SCD1 deficiency induces ER stress through mTORC1 activation. Rapamycin treatment of LKO mice reduces HCD-induced expression of the co-transcription factor PGC-1[alpha] and reduces ER stress. Moreover, dietary or endogenously synthesized oleate suppresses mTORC1 activation and reduces ER stress in the liver of LKO and SCD1 GKO mice, respectively. It could be concluded from these results that active mTORC1 induces ER stress through increasing PGC-1[alpha] in response to SCD1 deficiency. Overall, this work contributes to our understanding of the role of hepatic oleate in regulation of systemic metabolism and hepatic signaling pathways such as mTORC1.

Download or read book Sex and Gender Factors Affecting Metabolic Homeostasis Diabetes and Obesity written by Franck Mauvais-Jarvis and published by Springer. This book was released on 2017-12-08 with total page 630 pages. Available in PDF, EPUB and Kindle. Book excerpt: The book provides a reference for years to come, written by world-renowned expert investigators studying sex differences, the role of sex hormones, the systems biology of sex, and the genetic contribution of sex chromosomes to metabolic homeostasis and diseases. In this volume, leaders of the pharmaceutical industry present their views on sex-specific drug discovery. Many of the authors presented at the Keystone Symposium on “Sex and gender factors affecting metabolic homeostasis, diabetes and obesity” to be held in March 2017 in Lake Tahoe, CA. This book will generate new knowledge and ideas on the importance of gender biology and medicine from a molecular standpoint to the population level and to provide the methods to study them. It is intended to be a catalyst leading to gender-specific treatments of metabolic diseases. There are fundamental aspects of metabolic homeostasis that are regulated differently in males and females, and influence both the development of diabetes and obesity and the response to pharmacological intervention. Still, most preclinical researchers avoid studying female rodents due to the added complexity of research plans. The consequence is a generation of data that risks being relevant to only half of the population. This is a timely moment to publish a book on sex differences in diseases as NIH leadership has asked scientists to consider sex as a biological variable in preclinical research, to ensure that women get the same benefit of medical research as men.

Download or read book Lipid Metabolism written by Rodrigo Valenzuela Baez and published by IntechOpen. This book was released on 2013-01-23 with total page 474 pages. Available in PDF, EPUB and Kindle. Book excerpt: Lipids (fats and oils) are a wide range of organic molecules that serve several functions in organisms. Lipids are essential components of our diet, highlighting their important contribution in energy, representing 9 kcal/g (or 37.7 kJ/g), and by some components relevant to the metabolism, such as essential fatty acids, fat soluble vitamins and sterols (cholesterol and phytosterols). Besides this, lipids have key roles in human growth and development, along with promoting, preventing and/or participating in the origin or eventually in the treatment of various diseases. This book presents a systematic and comprehensive review about the structure and metabolism of lipids, particularly highlighting the importance of these molecules in the body and considering the interest of some lipids in health and disease.

Download or read book Metabolic and Clinical Perspectives on the Functions of the Liver written by Åke Nilsson and published by Cambridge Scholars Publishing. This book was released on 2024-02-07 with total page 267 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book describes how the liver executes and coordinates numerous physiological processes including metabolism, innate immunity, blood coagulation, bile secretion, and our symbiotic relation with the gut microbiome. It places the functions in clinical contexts, such as the pathogenesis of alcohol-related liver disease and metabolic (obesity) associated liver disease. It describes how in severe catabolic diseases such as cancer and sepsis, the liver redistributes bodily resources to increase chances of survival and recovery, and how the liver exemplifies many of the effects of diet and physical activity on health and wellbeing, via its regulation of glucose, lipid and cholesterol metabolism, and inflammation. The book is for professionals working in gastroenterology, hepatology, metabolic disorders, and many other medical disciplines, and for scientists and curious students of medicine, nutrition and biosciences.

Download or read book Short term regulation of hepatic lipogenesis by insulin and glucagon written by Anthonie C. Beynen and published by . This book was released on 1981 with total page 87 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book The Liver written by Irwin M. Arias and published by John Wiley & Sons. This book was released on 2020-03-09 with total page 1156 pages. Available in PDF, EPUB and Kindle. Book excerpt: Bridging the gap between basic scientific advances and the understanding of liver disease — the extensively revised new edition of the premier text in the field. The latest edition of The Liver: Biology and Pathobiology remains a definitive volume in the field of hepatology, relating advances in biomedical sciences and engineering to understanding of liver structure, function, and disease pathology and treatment. Contributions from leading researchers examine the cell biology of the liver, the pathobiology of liver disease, the liver’s growth, regeneration, metabolic functions, and more. Now in its sixth edition, this classic text has been exhaustively revised to reflect new discoveries in biology and their influence on diagnosing, managing, and preventing liver disease. Seventy new chapters — including substantial original sections on liver cancer and groundbreaking advances that will have significant impact on hepatology — provide comprehensive, fully up-to-date coverage of both the current state and future direction of hepatology. Topics include liver RNA structure and function, gene editing, single-cell and single-molecule genomic analyses, the molecular biology of hepatitis, drug interactions and engineered drug design, and liver disease mechanisms and therapies. Edited by globally-recognized experts in the field, this authoritative volume: Relates molecular physiology to understanding disease pathology and treatment Links the science and pathology of the liver to practical clinical applications Features 16 new “Horizons” chapters that explore new and emerging science and technology Includes plentiful full-color illustrations and figures The Liver: Biology and Pathobiology, Sixth Edition is an indispensable resource for practicing and trainee hepatologists, gastroenterologists, hepatobiliary and liver transplant surgeons, and researchers and scientists in areas including hepatology, cell and molecular biology, virology, and drug metabolism.

Download or read book The Molecular Nutrition of Fats written by Vinood Patel and published by Academic Press. This book was released on 2018-10-29 with total page 462 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Molecular Nutrition of Fats presents the nutritional and molecular aspects of fats by assessing their dietary components, their structural and metabolic effects on the cell, and their role in health and disease. Subject areas include molecular mechanisms, membranes, polymorphisms, SNPs, genomic wide analysis, genotypes, gene expression, genetic modifications and other aspects. The book is divided into three sections, providing information on the general and introductory aspects, the molecular biology of the cell, and the genetic machinery and its function. Topics discussed include lipid-related molecules, dietary lipids and lipid metabolism, high fat diets, choline, cholesterol, membranes, trans-and saturated fatty acids, and lipid rafts. Other sections provide comprehensive discussions on G protein-coupled receptors, micro RNA, transcriptomics, transcriptional factors, cholesterol, triacylglycerols, beta-oxidation, cholesteryl ester transfer, beta-oxidation, lysosomes, lipid droplets, insulin mTOR signaling and ligands, and more. - Summarizes molecular nutrition in health as related to fats - Discusses the impact of fats on cancer, heart disease, dementia, and respiratory and intestinal disease - Includes preclinical, clinical and population studies - Covers the genome, the whole body and whole communities - Includes key facts, a mini dictionary of terms and summary points

Download or read book Mechanisms of Insulin Action written by Alan R. Saltiel and published by Springer Science & Business Media. This book was released on 2007-10-05 with total page 223 pages. Available in PDF, EPUB and Kindle. Book excerpt: More than 18 million people in the United States have diabetes mellitus, and about 90% of these have the type 2 form of the disease. This book attempts to dissect the complexity of the molecular mechanisms of insulin action with a special emphasis on those features of the system that are subject to alteration in type 2 diabetes and other insulin resistant states. It explores insulin action at the most basic levels, through complex systems.

Download or read book Novel Food Ingredients for Weight Control written by C J K Henry and published by Elsevier. This book was released on 2007-04-30 with total page 375 pages. Available in PDF, EPUB and Kindle. Book excerpt: Obesity has become an epidemic of global proportions and is predicted to become the leading cause of death in many countries in the near future. As a result, weight control has become increasingly important for many consumers. Edited by a leading academic in the field, this important collection reviews research into the production and use of specific ingredients which can help to control body weight.Part one discusses ingredients implicated in the development of obesity such as sugars and lipids and the body's response to hunger and satiety. The second part of the book reviews particular ingredients derived from grains, fruit and vegetables, which can assist weight control. Chapters cover ?-glucans, oligosaccharides, starch and carbohydrates. Part three details dairy-based ingredients which can help regulate weight. It covers the use of food constituents such as calcium, conjugated linoleic acid (CLA), polyunsaturated fatty acids (PUFAs) and trans-free oils and fats.Written by an international team of contributors, this book provides food industry professionals and nutritionists with a valuable reference on ingredients for effective weight control. - Reviews research into the production and use of specific ingredients which can help to control body weight - Provides food industry professionals with essential information about particular ingredients that are effective in weight management - Valuable reference for nutritionists and food industry professionals