DOCSLIB.ORG

Regulation of Lipid Metabolism in Adipocytes and Hepatocytes by Hexarelin Through Scavenger Receptor CD36

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Regulation of Lipid Metabolism in Adipocytes and Hepatocytes by Hexarelin Through Scavenger Receptor CD36 Université de Montréal Regulation of lipid metabolism in adipocytes and hepatocytes by hexarelin through scavenger receptor CD36 par Amélie Rodrigue-Way Département de Biochimie Faculté de Médecine Thèse présentée à la Faculté des études supérieures en vue de l’obtention du grade de Philosophiae Doctor (Ph.D.) en Biochimie Avril 2011 © Amélie Rodrigue-Way, 2011 Université de Montréal Faculté des études supérieures Cette thèse intitulée : Regulation of lipid metabolism in adipocytes and hepatocytes by hexarelin through scavenger receptor CD36 présentée par : Amélie Rodrigue-Way a été évaluée par un jury composé des personnes suivantes : Luis Rokeach, président-rapporteur André Tremblay, directeur de recherche Grant Mitchell, membre du jury Frédéric Picard, examinateur externe Pierre Haddad, représentant du doyen de la FES iii Résumé Les sécrétines de l’hormone de croissance (GHRPs) sont de petits peptides synthétiques capables de stimuler la sécrétion de l’hormone de croissance à partir de l’hypophyse via leur liaison au récepteur de la ghréline GHS-R1a. Le GHRP hexaréline a été utilisé afin d’étudier la distribution tissulaire de GHS-R1a et son effet GH-indépendant. Ainsi, par cette approche, il a été déterminé que l’hexaréline était capable de se lier à un deuxième récepteur identifié comme étant le récepteur scavenger CD36. Ce récepteur possède une multitude de ligands dont les particules oxLDL et les acides gras à longue chaîne. CD36 est généralement reconnu pour son rôle dans l’athérogénèse et sa contribution à la formation de cellules spumeuses suite à l’internalisation des oxLDL dans les macrophages/monocytes. Auparavant, nous avions démontré que le traitement des macrophages avec l’hexaréline menait à l’activation de PPARƔ via sa liaison à GHS-R1a, mais aussi à CD36. De plus, une cascade d’activation impliquant LXRα et les transporteurs ABC provoquait également une augmentation de l’efflux du cholestérol. Une stimulation de la voie du transport inverse du cholestérol vers les particules HDL entraînait donc une diminution de l’engorgement des macrophages de lipides et la formation de cellules spumeuses. Puisque CD36 est exprimé dans de multiples tissus et qu’il est également responsable du captage des acides gras à longue chaîne, nous avons voulu étudier l’impact de l’hexaréline uniquement à travers sa liaison à CD36. Dans le but d’approfondir nos connaissances sur la régulation du métabolisme des lipides par CD36, nous avons choisi des types cellulaires jouant un rôle important dans l’homéostasie lipidique n’exprimant pas GHS-R1a, soient les adipocytes et les hépatocytes. L’ensemble de mes travaux démontre qu’en réponse à son interaction avec l’hexaréline, CD36 a le potentiel de réduire le contenu lipidique des adipocytes et des hépatocytes. Dans les cellules adipeuses, l'hexaréline augmente l’expression de plusieurs gènes impliqués dans la mobilisation et l’oxydation des acides gras, et induit également l’expression des marqueurs thermogéniques PGC-1α et UCP-1. De même, hexaréline iv augmente l’expression des gènes impliqués dans la biogenèse mitochondriale, un effet accompagné de changements morphologiques des mitochondries; des caractéristiques observées dans les types cellulaires ayant une grande capacité oxydative. Ces résultats démontrent que les adipocytes blancs traités avec hexaréline ont la capacité de se transformer en un phénotype similaire aux adipocytes bruns ayant l’habileté de brûler les acides gras plutôt que de les emmagasiner. Cet effet est également observé dans les tissus adipeux de souris et est dépendant de la présence de CD36. Dans les hépatocytes, nous avons démontré le potentiel de CD36 à moduler le métabolisme du cholestérol. En réponse au traitement des cellules avec hexaréline, une phosphorylation rapide de LKB1 et de l’AMPK est suivie d’une phosphorylation inhibitrice de l’HMG-CoA réductase (HMGR), l’enzyme clé dans la synthèse du cholestérol. De plus, la liaison d'hexaréline à CD36 provoque le recrutement d’insig-2 à HMGR, l’étape d’engagement dans sa dégradation. La dégradation de HMGR par hexaréline semble être dépendante de l’activité de PPARƔ et de l’AMPK. Dans le but d’élucider le mécanisme d’activation par hexaréline, nous avons démontré d’une part que sa liaison à CD36 provoque une déphosphorylation de Erk soulevant ainsi l’inhibition que celui-ci exerce sur PPARƔ et d’autre part, un recrutement de l’AMPK à PGC-1α expliquant ainsi une partie du mécanisme d’activation de PPARƔ par hexaréline. Les résultats générés dans cette thèse ont permis d’élucider de nouveaux mécanismes d’action de CD36 et d'approfondir nos connaissances de son influence dans la régulation du métabolisme des lipides. Mots-clés : Adipocytes, hépatocytes, CD36, hexaréline, PPARƔ, PGC1α, biogenèse mitochondriale, UCP-1, oxydation des acides gras, LKB1, AMPK, HMGR, insig-2, Erk, OSBPs. v Abstract Growth hormone releasing peptides (GHRPs) are small synthetic peptides aimed at stimulating GH release from the pituitary through their binding to ghrelin receptor known as growth hormone secretagogue receptor 1a (GHS-R1a). Using the GHRP, hexarelin to study tissue distribution of GHS-R1a and its GH-independent effect, it was observed that hexarelin was capable of binding to a second receptor identified as scavenger receptor CD36. While having multiple ligands, CD36 is mainly known for binding and internalizing oxLDL and long chain fatty acids. CD36 is thought to play a detrimental role in macrophage derived foam cell formation and development of atherosclerosis. Previously, we have shown that in macrophages, expressing both GHS-R1a and CD36, hexarelin promoted an activation of PPARƔ via GHS-R1a but also through its binding to CD36. This activation led to the induction of the LXRα-ABC transporters pathway and an increase in cholesterol efflux, reducing lipid-laden macrophage content. This positive effect on macrophages was reproduced in apolipoprotein E-null mice on a high fat diet treated with hexarelin. A significant reduction in the size of atherosclerotic lesions was observed while similar increases in the expression of PPARƔ, LXRα and ABC transporters occurred in isolated peritoneal macrophages. CD36 also plays a role in fatty acid uptake, and to further investigate the impact of the interaction of hexarelin with CD36, we aimed at evaluating the role of CD36 in regulating lipid metabolism in cells devoid of GHS-R1a such as adipocytes and hepatocytes. In the present thesis, we demonstrated through its interaction with hexarelin, the ability of CD36 to decrease intracellular lipid content in both adipocytes and hepatocytes. In adipocytes, hexarelin was able to increase the expression of several genes involved in fatty acid mobilization, fatty acid oxidation but also to induce the expression of the thermogenic markers, PGC-1α and UCP-1. In addition, hexarelin increased the expression of genes involved in mitochondrial biogenesis which was accompanied by mitochondrial morphological changes in agreement with what is usually seen in highly oxidative cells. In vi support of these findings, we also observed an increase in the activity of cytochrome c oxidase (a component of the respiratory chain) which could reflect an increase in oxidative phosphorylation. The results generated with cultured white adipocytes suggest the ability of hexarelin to promote changes toward a brown fat-like phenotype which also occurred in vivo and was dependent on the presence of CD36. In hepatocytes, CD36 was capable of regulating cholesterol metabolism by rapidly phosphorylating LKB1 and AMPK which subsequently resulted in the inactivating phosphorylation of HMG-CoA reductase, the rate- limiting enzyme in cholesterol synthesis. Hexarelin via CD36 also induced the recruitment of insig-2 to HMGR, the committed step in HMGR degradation while lifting the exerted inhibitory effect of Erk on nuclear receptor PPARƔ activity, and promoting the recruitment of AMPK to PPARƔ coactivator PGC-1α, suggesting an enhanced transcriptional potential of PPARƔ. The results generated during my graduate studies represent unique and novel mechanisms by which CD36 is capable of regulating lipid metabolism. Keywords : Adipocytes, hepatocytes, CD36, hexarelin, PPARγ, PGC1α, mitochondrial biogenesis, UCP-1, fatty acid oxidation, LKB1, AMPK, HMGR, insig-2, Erk, OSBPs. vii Table of contents Résumé..................................................................................................................................iii Abstract……….......................................................................................................................v List of Tables........................................................................................................................xi List of Figures......................................................................................................................xii Abbreviation list...................................................................................................................xiv Acknowledgements.............................................................................................................xxi CHAPTER 1: Introduction ..................................................................................................... 1 1 Growth hormone secretagogues ..................................................................................... 1 1.1 Design of growth hormone releasing peptides ....................................................... 1 1.2 Peptidomimetic growth hormone
Load more

Recommended publications
  • De Novo Phosphatidylcholine Synthesis in Intestinal Lipid Metabolism and Disease
    De Novo Phosphatidylcholine Synthesis in Intestinal Lipid Metabolism and Disease by John Paul Kennelly A thesis submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Nutrition and Metabolism Department of Agricultural, Food and Nutritional Science University of Alberta © John Paul Kennelly, 2018 Abstract Phosphatidylcholine (PC), the most abundant phospholipid in eukaryotic cells, is an important component of cellular membranes and lipoprotein particles. The enzyme CTP: phosphocholine cytidylyltransferase (CT) regulates de novo PC synthesis in response to changes in membrane lipid composition in all nucleated mammalian cells. The aim of this thesis was to determine the role that CTα plays in metabolic function and immune function in the murine intestinal epithelium. Mice with intestinal epithelial cell-specific deletion of CTα (CTαIKO mice) were generated. When fed a chow diet, CTαIKO mice showed normal lipid absorption after an oil gavage despite a ~30% decrease in small intestinal PC concentrations relative to control mice. These data suggest that biliary PC can fully support chylomicron output under these conditions. However, when acutely fed a high-fat diet, CTαIKO mice showed impaired intestinal fatty acid and cholesterol uptake from the intestinal lumen into enterocytes, resulting in lower postprandial plasma triglyceride concentrations. Impaired intestinal fatty acid uptake in CTαIKO mice was linked to disruption of intestinal membrane lipid transporters (Cd36, Slc27a4 and Npc1l1) and higher postprandial plasma Glucagon-like Peptide 1 and Peptide YY. Unexpectedly, there was a shift in expression of bile acid transporters to the proximal small intestine of CTαIKO mice, which was associated with enhanced biliary bile acid, PC and cholesterol output relative to control mice.
    [Show full text]
  • Aandp2ch25lecture.Pdf
    Chapter 25 Lecture Outline See separate PowerPoint slides for all figures and tables pre- inserted into PowerPoint without notes. Copyright © McGraw-Hill Education. Permission required for reproduction or display. 1 Introduction • Most nutrients we eat cannot be used in existing form – Must be broken down into smaller components before body can make use of them • Digestive system—acts as a disassembly line – To break down nutrients into forms that can be used by the body – To absorb them so they can be distributed to the tissues • Gastroenterology—the study of the digestive tract and the diagnosis and treatment of its disorders 25-2 General Anatomy and Digestive Processes • Expected Learning Outcomes – List the functions and major physiological processes of the digestive system. – Distinguish between mechanical and chemical digestion. – Describe the basic chemical process underlying all chemical digestion, and name the major substrates and products of this process. 25-3 General Anatomy and Digestive Processes (Continued) – List the regions of the digestive tract and the accessory organs of the digestive system. – Identify the layers of the digestive tract and describe its relationship to the peritoneum. – Describe the general neural and chemical controls over digestive function. 25-4 Digestive Function • Digestive system—organ system that processes food, extracts nutrients, and eliminates residue • Five stages of digestion – Ingestion: selective intake of food – Digestion: mechanical and chemical breakdown of food into a form usable by
    [Show full text]
  • Regulation of ATP-Binding Cassette Transporter Al in Cholesteryl Ester Storage Disease
    Regulation of ATP-Binding Cassette Transporter Al In Cholesteryl Ester Storage Disease by NICOLAS JAMES BILBEY B.Sc (Honours), Thompson Rivers University, 2006 A THESIS SUBMiTTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE in THE FACULTY OF GRADUATE STUDIES (Experimental Medicine) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) June 2009 © Nicolas James Bilbey, 2009 ABSTRACT Previous studies from the Francis laboratory have determined that regulation of ABCA1 expression is impaired in the lysosomal cholesterol storage disorder Niemann-Pick type C (NPC) disease, the presumed reason for the low plasma HDL-cholesterol (HDL-C) levels found in the majority of NPC disease patients. Cholesteryl ester storage disease (CESD) is another lysosomal cholesterol storage disorder, resulting from deficiency in lysosomal acid lipase (LAL). CESD patients develop premature atherosclerosis, possibly related to their known low plasma HDL-C levels. We hypothesized that in CESD the reduced activity of LAL also leads to impaired ABCA1 regulation and HDL formation due to the decrease in release of unesterified cholesterol from lysosomes. Our results show that human CESD fibroblasts exhibit a blunted increase in ABCA1 mRNA and protein in response to addition of low density lipoprotein (LDL) to the medium when compared to normal human fibroblasts. Efflux of LDL-derived cholesterol radiolabel and mass to apolipoprotein A-I-containing medium was markedly reduced in CESD fibroblasts compared to normal fibroblasts. Cellular radiolabeled cholesteryl ester derived from LDL and total cell cholesteryl ester mass was increased in CESD compared to normal cells. Delivery of an adenovirus expressing full length human lysosomal acid lipase (Ad-hLAL) results in correction of LAL activity and an increase ABCA1 protein expression, as well as correction of cholesterol and phospholipid release to apoA-I and normalization of cholesteryl ester levels in the CESD fibroblasts.
    [Show full text]
  • University of Cincinnati
    UNIVERSITY OF CINCINNATI Date:___________________ I, _________________________________________________________, hereby submit this work as part of the requirements for the degree of: in: It is entitled: This work and its defense approved by: Chair: _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ ii Intestinal lipid uptake and secretion of VLDL and chylomicron By: Andromeda Nauli August 2005 Previous degree: Bachelor of Science in Biomedical Sciences Degree to be conferred: Ph.D. Department of Pathology and Laboratory Medicine College of Medicine University of Cincinnati Committee chair: Patrick Tso, Ph.D. iii ABSTRACT Despite decades of research, our understanding of intestinal lipid absorption is limited. In this Ph.D. thesis, I have dealt with two main aspects of intestinal lipid absorption, namely the uptake of lipids and the formation and secretion of triacylglycerol-rich lipoproteins (very low density lipoproteins [VLDL] and chylomicrons). In terms of uptake, CD36 is one of the plasma membrane proteins implicated in mediating lipid uptake by the intestine. In order to test this hypothesis, we utilized the CD36 knockout mouse model equipped with intraduodenal and lymph cannulas. Our studies showed that the disruption of the CD36 gene led to a significant decrease in the uptake of cholesterol but not of fatty acids. Interestingly, the role of CD36 was not limited to uptake but also appeared to affect the formation and secretion of chylomicrons, the major lipoproteins carrying the absorbed dietary fat from the gut (Chapter 2). It was first proposed by Tso et al. (202) that the small intestine secretes both VLDL and chylomicrons. Previous work by Vahouny et al. (212) suggested that female rats produced more VLDL than male rats.
    [Show full text]
  • Fat Digestion: Intestinal Lipolysis and Product Absorption
    Nutrition of the Lov: Birthweight Infant, edited by B. L. Salle and P. R. Swyer. Nestte Nutrition Workshop Series, Vol. 32. Nestec Ltd., Vevey/Raven Press, Ltd., New York © 1993. Fat Digestion: Intestinal Lipolysis and Product Absorption Lars Blackberg and *Olle Hernell Department of Medical Biochemistry and Biophysics, and 'Department of Pediatrics, University of Umea, S-901 85 Umea, Sweden Fat digestion in the breastfed newborn infant is a process catalyzed by three Upases. The process is initiated in stomach contents by gastric lipase and continues in the upper part of the small intestine by pancreatic colipase-dependent lipase and human milk bile-salt-stimulated lipase (BSSL). Development of powerful techniques in molecular biology has made it possible to gain better insight into the structure of these lipases, which is necessary for a detailed understanding of the different functional aspects. We shall briefly discuss recent advances in structural knowledge of the lipases as well as their functional implica- tions. We shall focus mainly on the human enzymes but, when relevant, also discuss corresponding enzymes of other species. GASTRIC LIPASE Gastric lipolysis and lipase activities of preduodenal origin have been recognized for many years. In humans the responsible enzyme is secreted by the chief cells of the gastric mucosa (1). The primary sequence of this 52-kDa glycoprotein is known through cloning and sequencing of cDNA (2). The tissue of origin differs between species but the amino acid sequence is highly conserved (2-5). Although, gastric lipase is of similar molecular size to colipase-dependent lipase the sequence shows only limited homology.
    [Show full text]
  • 299 INTESTINAL LIPID ABSORPTION and TRANSPORT Cam T. Phan
    [Frontiers in Bioscience 6, d299-319, March 1, 2001] INTESTINAL LIPID ABSORPTION AND TRANSPORT Cam T. Phan and Patrick Tso Department of Pathology, University of Cincinnati Medical Center, 231 Albert Sabin Way, Cincinnati, OH 45267 TABLE OF CONTENTS 1. Abstract 2. Introduction 3. Dietary lipids 4. Structured lipids 5. Digestion of dietary lipids and structured lipids 5.1. Gastric lumen 5.2. Intestinal lumen 5.3. Digestion of phospholipid 5.4. Digestion of cholesteryl ester 6. Uptake of dietary lipids by enterocytes 6.1. Importance of micellar solubilization 6.2. Importance of unilamellar vesicles 6.3. Uptake of fat digestion products by enterocytes 7. Resynthesis of triglycerides and formation of chylomicrons 7.1. Monoglycerides and fatty acid 7.2. Phospholipids 7.3. Cholesterol 8. Assembly of intestinal lipoproteins 9. Clinical disorders of intestinal lipid transport 10. Acknowledgements 11. References 1. ABSTRACT The purpose of this review is to update the reader lacks the key lipid reesterification enzymes. Finally, the on our current knowledge of the digestion, uptake, and mechanisms of the formation and secretion of chylomicrons is transport of dietary lipid. In particular, it discusses how described and clinical disorders discussed. intestinal lipid transporters may play a role in the uptake of lipids by the enterocytes, and how chylomicrons are formed in 2. INTRODUCTION the enterocytes and packaged for export into the lymphatic system through exocytosis. The classification and properties Many past reviews have been written on the of lipids is first described followed by a discussion of digestion and absorption of lipid and the formation of structured lipids and their role in human nutrition.
    [Show full text]
  • Gastric Digestive Function
    Gastrointestinal Functions, edited by Edgard E. Delvin and Michael J. Lentze. Nestle Nutrition Workshop Series. Pediatric Program, Vol. 46. Nestec Ltd.. Vevey/Lippincott Williams & Wilkins. Philadelphia © 2001. Gastric Digestive Function Daniel Menard and Jean-Rene Basque Department of Anatomy and Cell Biology, Faculty of Medicine, University of Sherbrooke, Quebec, Canada The gastric epithelium not only has a protective barrier function (against hydro- chloric acid, peptidases, Helicobacter pylori, and so on) and a primary role in epithe- lial restitution (ulcer healing), but it also has specific digestive functions. The gastric mucosa is responsible for the secretion of luminal compounds such as mucus, hydro- chloric acid, pepsinogen, and lipase. One of the main purposes of gastric secretion is the digestion of dietary proteins. This involves the release of different pepsinogens (Pgl-5) by the fundic and antral gastric glands (1). These inactive proenzymes are synthesized and packaged into secretory granules of surface or glandular epithelial cells. Under acidic conditions, these secreted proenzymes are autocatalytically cleaved to generate their active form—pepsins (pepsin, prochymosin, progastricsin)—which are representative members of a group of proteolytic enzymes classified as aspartic proteases (2). In humans, pepsinogen 5 (Pg5), which is specifically synthesized and secreted by zymogenic chief cells, plays a primary role in the initiation of protein digestion and the proteolysis of collagen (the protein component of meat). Although pepsinogen has been a subject of research since the 19th century (3), knowledge acquired over the last decade on the functions of the human stomach has expanded to include a significant role in fat digestion (4). In contrast to pepsin, the presence of a true gastric lipase has been the subject of a long controversy (4).
    [Show full text]
  • Lingual Lipase and Its Role in the Digestion of Dietary Lipid
    Lingual Lipase and Its Role in the Digestion of Dietary Lipid MAnGrr HAMOSH and RoBErT 0. Scow From the Section on Endocrinology, Laboratory of Nutrition and Endocrinology, National Institute of Arthritis and Metabolic Diseases, Bethesda, Maryland 20014 A B S T R A C T The serous glands of rat tongue were saliva of calves contains a lipolytic activity, called "pre- found to contain a potent lipolytic enzyme which hydro- gastric esterase," which hydrolyzes triglyceride to FFA lyzed triglyceride to mostly diglyceride and free fatty in the stomach (11). Glandular tissue from the back re- acids (FFA) at pH 4.5-5.4. Homogenates of lingual se- gion of the tongue, the glossoepiglottic area of the rous glands from adult rats hydrolyzed 40-70 mmol of pharynx, and the pharyngeal end of the esophagus also triglyceride/g per h. The soft palate, anterior oral pharyn- contained the activity (12). Therefore, the secretory geal wall, and lateral oral pharyngeal glands also con- tissues of the mouth of suckling and adult rats were ex- tained the activity, but at a much lower level. The lipo- amined for lipolytic activity. This paper describes a po- lytic activity was also found in saliva collected through tent lipase found in the tongue and its possible role in the an esophageal cannula and in stomach contents of rats digestion of triglyceride. fed a fat-rich meal. The stomach contained very little activity, however, when saliva was excluded. Lipolytic METHODS activity was not found in the stomach wall or in the Animals. Adult female (Charles River, Charles River parotid, submandibular, and sublingual glands.
    [Show full text]
  • Enzymes Involved in Lipid Digestion A
    Enzymes involved in lipid digestion A. Salhi, F. Carriere, Myriam M.-L. Grundy, A. Aloulou To cite this version: A. Salhi, F. Carriere, Myriam M.-L. Grundy, A. Aloulou. Enzymes involved in lipid digestion. Myriam M.-L. Grundy; Peter J. Wilde. Bioaccessibility and digestibility of lipids from food, Springer Interna- tional Publishing, pp.3-28, 2021, 978-3-030-56908-2. 10.1007/978-3-030-56909-9_1. hal-03146298 HAL Id: hal-03146298 https://hal.archives-ouvertes.fr/hal-03146298 Submitted on 19 Feb 2021 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Preprint of DOI: 10.1007/978-3-030-56909-9_1 Enzymes involved in lipid digestion Salhi, A. a, b , Carriere, F. b, Grundy, M. M.L c, and Aloulou, A. a a Laboratoire de Biochimie et de Genie Enzymatique des Lipases, ENIS, Universite de Sfax, 3038, Sfax, Tunisia b Aix Marseille Univ, CNRS, BIP, UMR7281, 31 Chemin Joseph Aiguier, 13402, Marseille Cedex 9, France c School of Agriculture, Policy and Development, Sustainable Agriculture and Food Systems Division, University of Reading, Earley Gate, Reading, RG6 6AR, UK Lipid digestion is a complex process that takes place at the lipid-water interface and involves various lipolytic enzymes present predominantly in the stomach and the small intestine (Carey, Small, & Bliss, 1983).
    [Show full text]
  • Digestion of Human Milk Fat in Healthy Infants
    NUTRITION RESEARCH 83 (2020) 15– 29 Available online at www.sciencedirect.com ScienceDirect www.nrjournal.com Review Article Digestion of human milk fat in healthy infants Xuan He a, b, Shannon M cClorry a, Olle Hernell c, Bo Lönnerdal a, Carolyn M. Slupsky a, b,⁎ a Department of Nutrition, Davis, One Shields Ave, Davis, CA 95616, USA b Department of Food Science and Technology, University of California, Davis, One Shields Ave, Davis, CA 95616, USA c Department of Clinical Sciences, Pediatrics, Umeå University, SE 901 85 Umeå, Sweden ARTICLE INFO ABSTRACT Article history: Lipid digestion is critical for infant development, and yet, the interconnection between lipid Received 17 March 2020 digestion and the microbiota is largely understudied. This review focuses on digestion of the Revised 2 August 2020 human milk fat globule and summarizes the current understanding of the mechanisms Accepted 7 August 2020 underlying this process in infants. We first discuss the partial hydrolysis of milk fat in the stomach, which leads to rearrangement of lipid droplets, creating a lipid-water interface Keywords: necessary for duodenal lipolysis. In the first few months of life, secretion of pancreatic Infant triglyceride lipase, phospholipase A2, and bile salts is immature. The dominant lipases aiding fat Neonate digestion in the newborn small intestine are therefore pancreatic lipase-related protein 2 and Lipid digestion bile salt–stimulated lipase from both the exocrine pancreas and milk. We summarize the Milk fat globule interaction between ionic fatty acids and cations to form insoluble fatty acid soaps and how it is Gut microbiota influenced by various factors, including cation availability, pH, and bile salt concentration, as well as saturation and chain length of fatty acids.Wefurtherarguethattheformationofthe soap complex does not contribute to lipid bioavailability.
    [Show full text]
  • The Functional Role of CD36 Involved in Fatty Acid Transduction
    Utah State University DigitalCommons@USU All Graduate Theses and Dissertations Graduate Studies 5-2014 The Functional Role of CD36 Involved in Fatty Acid Transduction Han Xu Utah State University Follow this and additional works at: https://digitalcommons.usu.edu/etd Part of the Biology Commons Recommended Citation Xu, Han, "The Functional Role of CD36 Involved in Fatty Acid Transduction" (2014). All Graduate Theses and Dissertations. 2172. https://digitalcommons.usu.edu/etd/2172 This Dissertation is brought to you for free and open access by the Graduate Studies at DigitalCommons@USU. It has been accepted for inclusion in All Graduate Theses and Dissertations by an authorized administrator of DigitalCommons@USU. For more information, please contact [email protected]. THE FUNCTIONAL ROLE OF CD36 INVOLVED IN FATTY ACID TRANSDUCTION By Han Xu A dissertation submitted in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY In Biology Approved: Timothy A. Gilbertson, Ph.D. David A. York, Ph.D. Major Professor Committee Member MieJung Park-York, Ph.D. Michael Lefevre, Ph.D. Committee Member Committee Member Anhong Zhou, Ph.D. Mark R. McLellan, Ph.D. Committee Member Vice President for Research and Dean of the School of Graduate Studies UTAH STATE UNIVERSITY Logan, Utah 2013 ii Copyright © Han Xu 2013 All Rights Reserved iii ABSTRACT The Functional Role of CD36 Involved in Fatty Acid Transduction by Han Xu, Doctor of Philosophy Utah State University, 2013 Major Professor: Dr. Timothy A. Gilbertson Department: Biology The multifunctional fatty acid (FA) binding protein, Cluster of Differentiation 36 (CD36), has been found to be expressed in a variety of tissues where it is involved in multiple fat-related biological processes, such as lipid metabolism in mammals and the detection of lipid-like pheromones in insects.
    [Show full text]
  • Principles of Physiology of Lipid Digestion
    282 Principles of Physiology of Lipid Digestion E. Bauer*, S. Jakob1 and R. Mosenthin Institute of Animal Nutrition, University of Hohenheim, Emil-Wolff-Str. 10, 70599 Stuttgart, Germany ABSTRACT : The processing of dietary lipids can be distinguished in several sequential steps, including their emulsification, hydrolysis and micellization, before they are absorbed by the enterocytes. Emulsification of lipids starts in the stomach and is mediated by physical forces and favoured by the partial lipolysis of the dietary lipids due to the activity of gastric lipase. The process of lipid digestion continues in the duodenum where pancreatic triacylglycerol lipase (PTL) releases 50 to 70% of dietary fatty acids. Bile salts at low concentrations stimulate PTL activity, but higher concentrations inhibit PTL activity. Pancreatic triacylglycerol lipase activity is regulated by colipase, that interacts with bile salts and PTL and can release bile salt mediated PTL inhibition. Without colipase, PTL is unable to hydrolyse fatty acids from dietary triacylglycerols, resulting in fat malabsorption with severe consequences on bioavailability of dietary lipids and fat-soluble vitamins. Furthermore, carboxyl ester lipase, a pancreatic enzyme that is bile salt-stimulated and displays wide substrate reactivities, is involved in lipid digestion. The products of lipolysis are removed from the water-oil interface by incorporation into mixed micelles that are formed spontaneously by the interaction of bile salts. Monoacylglycerols and phospholipids enhance the ability of bile salts to form mixed micelles. Formation of mixed micelles is necessary to move the non-polar lipids across the unstirred water layer adjacent to the mucosal cells, thereby facilitating absorption. (Asian-Aust. J.
    [Show full text]