The Role of Sex Steroids in White Adipose Tissue Adipocyte Function

Total Page:16

File Type:pdf, Size:1020Kb

The Role of Sex Steroids in White Adipose Tissue Adipocyte Function REPRODUCTIONREVIEW PROOF ONLY The role of sex steroids in white adipose tissue adipocyte function A E Newell-Fugate Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, Texas, USA Correspondence should be addressed to A E Newell-Fugate; Email: [email protected] Abstract With the increasing knowledge that gender influences normal physiology, much biomedical research has begun to focus on the differential effects of sex on tissue function. Sexual dimorphism in mammals is due to the combined effects of both genetic and hormonal factors. Hormonal factors are mutable particularly in females in whom the estrous cycle dominates the hormonal milieu. Given the severity of the obesity epidemic and the fact that there are differences in the obesity rates in men and women, the role of sex in white adipose tissue function is being recognized as increasingly important. Although sex differences in white adipose tissue distribution are well established, the mechanisms affecting differential function of adipocytes within white adipose tissue in males and females remain largely understudied and poorly understood. One of the largest differences in the endocrine environment in males and females is the concentration of circulating androgens and estrogens. This review examines the effects of androgens and estrogens on lipolysis/lipogenesis, adipocyte differentiation, insulin sensitivity and adipokine production in adipocytes from white adipose tissue with a specific emphasis on the sexual dimorphism of adipocyte function in white adipose tissue during both health and disease. Reproduction (2017) 153 R133–R149 Introduction Gynecoid adipose tissue distribution is associated with lower risks for type II diabetes and coronary artery disease Historically, the effects of gender have been largely (Manolopoulos et al. 2010). Recent evidence suggests ignored across biomedical research. Subsequent to this that sex-specific single nucleotide polymorphisms practice, studies utilizing immortalized cell lines, single- (SNPs) help direct fat distribution in males and sex animal models or human patients representing only females and epigenetically regulate lipid homeostasis one sex have resulted in the inability to determine (Sung et al. 2016). Visceral adipocytes exhibit similar whether research findings are applicable to both sexes basal lipolysis but higher catecholamine-stimulated (Johnson et al. 2014). In recent years, concerns initially lipolysis compared to subcutaneous adipocytes in raised about the lack of women in clinical studies both sexes (Tchernof et al. 2006, Boivin et al. 2007). (Kim et al. 2010) have resulted in the National Institutes Lipoprotein lipase (LPL) activity and glucose uptake are of Health (NIH) requiring sex balance in research lower in visceral adipocytes than those in subcutaneous involving cells and animal models (Clayton & Collins adipocytes in women who also have smaller adipocytes, 2014). Furthermore, sex differences in the relative risk but is similar among adipocytes from these two white for diseases such as cancer, obesity, coronary heart adipose tissue (WAT) depots in men (Edens et al. 1993, disease and autoimmune diseases are well established Boivin et al. 2007). Differences in adipocyte function (Becker et al. 2005). within different WAT depots may be related to the Sexual dimorphism in mammals is the result of differences in WAT distribution in women and men. both genetic and hormonal factors (Money & Ehrhardt Disease states in women associated with elevated 1972). Genetic factors derived from chromosomes circulating androgen concentrations such as are relatively permanent, whereas hormonal factors polycystic ovary syndrome (PCOS) or congenital are mutable, particularly in females in whom the adrenal hyperplasia may result in android adipose hypothalamic–pituitary–gonadal axis and the menstrual tissue accumulation and, subsequently, an increased cycle predominantly control the hormonal milieu propensity for insulin resistance and atherosclerosis (Christensen et al. 2012). Women have a higher (Sirmans & Pate 2014). By contrast, overweight men percentage body fat than men and tend to distribute with visceral adipose tissue accumulation are at risk for their adipose tissue in the hips and thighs (‘gynecoid’), hypogonadism, low androgen levels and type II diabetes whereas men tend to distribute their adipose tissue (Dandona & Dhindsa 2011). Furthermore, menopause, abdominally (‘android’) (Karastergiou et al. 2012). © 2017 Society for Reproduction and Fertility DOI: 10.1530/REP-16-0417 ISSN 1470–1626 (paper) 1741–7899 (online) Online version via www.reproduction-online.org Downloaded from Bioscientifica.com at 09/27/2021 08:19:27AM via free access 10.1530/REP-16-0417 R134 A E Newell-Fugate which is due to the onset of ovarian inactivity and its effects through binding to either classical estrogen results in decreased PROOFestrogen and progesterone levels, receptors ONLY (ER), which are nuclear transcription factors is accompanied by increases in overall adiposity, expressed widely throughout the adipose tissue particularly due to visceral adipose tissue accumulation compartment (Mizutani et al. 1994, Dieudonné et al. (Tchernof & Poehlman 1998). The aforementioned body 1998), or to non-classical ER like G-protein-coupled transitions and disease states underscore the importance estrogen receptor (GPER), which are membrane-bound of sex steroid hormones to WAT adipocyte function. receptors (Prossnitz & Barton 2011). There are two Although sex differences in WAT distribution are well classes of classical ERs, ER alpha (ERα) and ER beta established, the mechanisms affecting differential WAT (ERβ), each of which has a distinct tissue distribution adipocyte function in males and females are poorly (Koehler et al. 2005). In addition to differential tissue understood. Given the severity of the obesity epidemic expression, the ligand binding domains of ERα and ERβ and the fact that there are differences in the rate at which are unique, which allows selective ligands to target obesity affects men and women (Flegal et al. 2016) one or the other pathway (Koehler et al. 2005). With ( et al. 2016), the role of sex in WAT adipocyte function respect to reproductive tissues, ERα is uterotropic and is recognized as increasingly important. Although other found in the ovarian stroma and breast, whereas ERβ factors besides sex steroid levels vary and account for is in the ovarian granulosa cells (Korach et al. 2003). differences between WAT adipocyte function in males and Current literature suggests that ERα modulates anti- females, sex steroids play a central role in the regulation lipogenesis, insulin sensitivity and glucose tolerance, of many tissues in the body (Wierman 2007). Additionally, and reduction of body weight and WAT mass (Blüher it is likely that sex differences in cell types other than 2013). In contrast, ERβ appears to be detrimental for adipocytes within WAT also account for differences in the maintenance of glucose and lipid homeostasis metabolism between males and females. However, this (Foryst-Ludwig & Kintscher 2010). Recent evidence review focuses on the effect of sex steroids (androgens and also indicates a role for the non-genomic regulation estrogens) on WAT adipocyte function including lipolysis/ of WAT lipogenesis by GPER, but the findings between lipogenesis, adipocyte differentiation, insulin sensitivity publications differ (Haas et al. 2009, Isensee et al. 2009, and adipokine production/secretion. Particular emphasis Mårtensson et al. 2009, Sharma et al. 2013). Several is paid in this review to the sexual dimorphism of WAT studies have demonstrated that male GPER-deficient adipocyte function in the context of steroid hormones in (GPERKO) mice suffer from increased WAT mass and both health (i.e. menopause) and disease (i.e. polycystic decreased insulin sensitivity, whereas female GPERKO ovary syndrome in women, hypogonadism in men). mice have decreased weights (Mårtensson et al. 2009, Sharma et al. 2013). Other studies have shown that both male and female GPERKO mice have increased WAT, Estrogens particularly in the visceral compartment (Haas et al. Lipolysis and lipogenesis 2009). Finally, other studies have found no differences in body weight and adiposity between GPERKO and Lipolysis and lipogenesis of adipose tissue assists wild-type male or female mice fed either a control with energy release and energy storage in the body or high-fat diet (Isensee et al. 2009). Research using (Thomas et al. 1979) (Fig. 1). Estradiol (E2) renders knock-out rodent models has demonstrated that both Figure 1 Overview of adipocyte metabolism. After a meal, energy enters the adipocyte through several mechanisms: 1) direct absorption of fatty acids (FA) from the blood stream, 2) uptake of glucose through GLUT4 receptors on the adipocyte cell membrane and 3) cleavage of triglycerides (TG) into fatty acids via lipoprotein lipase (LPL) made by the adipocyte. Catecholamines stimulate release of fatty acids from triglycerides in the triglyceride pool by stimulating hormone- sensitive lipase (HSL; 4). Insulin stimulates uptake of glucose via GLUT4 (2) but inhibits lipolysis via HSL (5). Fatty acids can be released from the adipocyte after lipolysis (6). Reproduction (2017) 153 R133–R149 www.reproduction-online.org Downloaded from Bioscientifica.com at 09/27/2021 08:19:27AM via free access Sex steroids and adipocyte function R135 cytosolic and membrane-bound sex steroid receptors It is
Recommended publications
  • Effects of Glucagon, Glycerol, and Glucagon Plus Glycerol On
    Iowa State University Capstones, Theses and Graduate Theses and Dissertations Dissertations 2011 Effects of glucagon, glycerol, and glucagon plus glycerol on gluconeogenesis, lipogenesis, and lipolysis in periparturient Holstein cows Nimer Mehyar Iowa State University Follow this and additional works at: https://lib.dr.iastate.edu/etd Part of the Biochemistry, Biophysics, and Structural Biology Commons Recommended Citation Mehyar, Nimer, "Effects of glucagon, glycerol, and glucagon plus glycerol on gluconeogenesis, lipogenesis, and lipolysis in periparturient Holstein cows" (2011). Graduate Theses and Dissertations. 11923. https://lib.dr.iastate.edu/etd/11923 This Thesis is brought to you for free and open access by the Iowa State University Capstones, Theses and Dissertations at Iowa State University Digital Repository. It has been accepted for inclusion in Graduate Theses and Dissertations by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. Effects of glucagon, glycerol, and glucagon plus glycerol on gluconeogenesis, lipogenesis, and lipolysis in periparturient Holstein cows by Nimer Mehyar A thesis submitted to graduate faculty in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE Major: Biochemistry Program of Study Committee: Donald C. Beitz, Major Professor Ted W. Huiatt Kenneth J. Koehler Iowa State University Ames, Iowa 2011 Copyright Nimer Mehyar, 2011. All rights reserved ii To My Mother To Ghada Ali, Sarah, and Hassan
    [Show full text]
  • THE AEROBIC (Air-Robic!) PATHWAYS
    THE AEROBIC (air-robic!) PATHWAYS Watch this video on aerobic glycolysis: http://ow.ly/G5djv Watch this video on oxygen use: http://ow.ly/G5dmh Energy System 1 – The Aerobic Use of Glucose (Glycolysis) This energy system involves the breakdown of glucose (carbohydrate) to release energy in the presence of oxygen. The key to this energy system is that it uses OXYGEN to supply energy. Just like the anaerobic systems, there are many negatives and positives from using this pathway. Diagram 33 below summarises the key features of this energy system. When reading the details on the table keep in mind the differences between this and the previous systems that were looked at. In this way a perspective of their features can be appreciated and applied. Diagram 33: The Key Features of the Aerobic Glycolytic System Highlight 3 key features in the diagram that are important to the functioning of this system. 1: ------------------------------------------------------------------------------------------------------------------------------------------------------- 2: ------------------------------------------------------------------------------------------------------------------------------------------------------- 3: ------------------------------------------------------------------------------------------------------------------------------------------------------- Notes ---------------------------------------------------------------------------------------------------------------------------------------------------------- ----------------------------------------------------------------------------------------------------------------------------------------------------------
    [Show full text]
  • Adipocyte Glucocorticoid Receptor Is Important in Lipolysis and Insulin Resistance Due to Exogenous Steroids, but Not Insulin Resistance Caused by High Fat Feeding
    Adipocyte glucocorticoid receptor is important in lipolysis and insulin resistance due to exogenous steroids, but not insulin resistance caused by high fat feeding The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation Shen, Yachen, Hyun Cheol Roh, Manju Kumari, and Evan D. Rosen. 2017. “Adipocyte glucocorticoid receptor is important in lipolysis and insulin resistance due to exogenous steroids, but not insulin resistance caused by high fat feeding.” Molecular Metabolism 6 (10): 1150-1160. doi:10.1016/j.molmet.2017.06.013. http:// dx.doi.org/10.1016/j.molmet.2017.06.013. Published Version doi:10.1016/j.molmet.2017.06.013 Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:34492181 Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use#LAA Original Article Adipocyte glucocorticoid receptor is important in lipolysis and insulin resistance due to exogenous steroids, but not insulin resistance caused by high fat feeding Yachen Shen 1,4,5, Hyun Cheol Roh 1,5, Manju Kumari 1, Evan D. Rosen 1,2,3,* ABSTRACT Objective: The critical role of adipose tissue in energy and nutrient homeostasis is influenced by many external factors, including overnutrition, inflammation, and exogenous hormones. Prior studies have suggested that glucocorticoids (GCs) in particular are major drivers of physiological and pathophysiological changes in adipocytes. In order to determine whether these effects directly require the glucocorticoid receptor (GR) within adipocytes, we generated adipocyte-specific GR knockout (AGRKO) mice.
    [Show full text]
  • Glycolysis and Glyceroneogenesis In
    GLYCOLYSIS AND GLYCERONEOGENESIS IN ADIPOCYTES: EFFECTS OF ROSIGLITAZONE, AN ANTI-DIABETIC DRUG By SOREIYU UMEZU Bachelor of Science in Biochemistry and Molecular Biology Oklahoma State University Stillwater, OK 2005 Submitted to the Faculty of the Graduate College of the Oklahoma State University in partial fulfillment of the requirements for the Degree of DOCTOR OF PHILOSOPHY July, 2010 GLYCOLYSIS AND GLYCERONEOGENESIS IN ADIPOCYTES: EFFECTS OF ROSIGLITAZONE, AN ANTI-DIABETIC DRUG Dissertation Approved: Dr. Jose L Soulages Dissertation Adviser Dr. Chang-An Yu Dr. Andrew Mort Dr. Jack Dillwith Dr. A. Gordon Emslie Dean of the Graduate College ii ACKNOWLEDGMENTS First, I would like to immensely thank my advisor, Dr. Jose Soulages, for his support and guidance throughout my graduate studies. Without Dr. Soulages extensive expertise and knowledge along with his sense of humor I would not have achieved my goal of obtaining my Doctorate in Biochemistry. I would also like to thank Dr. Estela Arrese for her kind and generous advice. Both Dr. Soulages and Dr. Arrese have made a tremendous impact on me personally and professionally. I would like to thank all the members of my committee: Dr. Chang-An Yu, Dr. Andrew Mort, and Dr. Jack Dillwith who have devoted their time reading my dissertation and their patience for my procrastination. Their support and guidance has been invaluable and extremely appreciative. Most importantly, I want to acknowledge my parents: (Dr.) Mrs. Fumie Umezu and (Dr.) Mr. Yasuiki Umezu, for their unwavering support of me throughout my time in the U.S. and for suffering me while I’m doing whatever I want in my life.
    [Show full text]
  • Genomic and Non-Genomic Actions of Glucocorticoids on Adipose Tissue Lipid Metabolism
    International Journal of Molecular Sciences Review Genomic and Non-Genomic Actions of Glucocorticoids on Adipose Tissue Lipid Metabolism Negar Mir 1, Shannon A. Chin 1 , Michael C. Riddell 2 and Jacqueline L. Beaudry 1,* 1 Department of Nutritional Sciences, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada; [email protected] (N.M.); [email protected] (S.A.C.) 2 Faculty of Health, School of Kinesiology and Health Science, York University, Toronto, ON M3J 1P3, Canada; [email protected] * Correspondence: [email protected] Abstract: Glucocorticoids (GCs) are hormones that aid the body under stress by regulating glucose and free fatty acids. GCs maintain energy homeostasis in multiple tissues, including those in the liver and skeletal muscle, white adipose tissue (WAT), and brown adipose tissue (BAT). WAT stores energy as triglycerides, while BAT uses fatty acids for heat generation. The multiple genomic and non-genomic pathways in GC signaling vary with exposure duration, location (adipose tissue depot), and species. Genomic effects occur directly through the cytosolic GC receptor (GR), regulating the expression of proteins related to lipid metabolism, such as ATGL and HSL. Non-genomic effects act through mechanisms often independent of the cytosolic GR and happen shortly after GC exposure. Studying the effects of GCs on adipose tissue breakdown and generation (lipolysis and adipogenesis) leads to insights for treatment of adipose-related diseases, such as obesity, coronary disease, and cancer, but has led to controversy among researchers, largely due to the complexity of the process. This paper reviews the recent literature on the genomic and non-genomic effects of GCs on WAT and Citation: Mir, N.; Chin, S.A.; Riddell, BAT lipolysis and proposes research to address the many gaps in knowledge related to GC activity M.C.; Beaudry, J.L.
    [Show full text]
  • Unbalanced Lipolysis Results in Lipotoxicity and Mitochondrial Damage in Peroxisome-Deficient Pex19 Mutants
    M BoC | ARTICLE Unbalanced lipolysis results in lipotoxicity and mitochondrial damage in peroxisome-deficient Pex19 mutants Margret H. Bülowa,*, Christian Wingena, Deniz Senyilmazb, Dominic Gosejacoba, Mariangela Socialea, Reinhard Bauera, Heike Schulzec, Konrad Sandhoffc, Aurelio A. Telemanb, Michael Hocha,*, and Julia Sellina,* aDepartment of Molecular Developmental Biology, Life & Medical Sciences Institute (LIMES), University of Bonn, 53115 Bonn, Germany; bDivision of Signal Transduction in Cancer and Metabolism, German Cancer Research Center, 69120 Heidelberg, Germany; cDepartment of Membrane Biology & Lipid Biochemistry, Life & Medical Sciences Institute (LIMES), Kekulé Institute of Organic Chemistry and Biochemistry, University of Bonn, 53121 Bonn, Germany ABSTRACT Inherited peroxisomal biogenesis disorders (PBDs) are characterized by the ab- Monitoring Editor sence of functional peroxisomes. They are caused by mutations of peroxisomal biogenesis Thomas D. Fox factors encoded by Pex genes, and result in childhood lethality. Owing to the many metabolic Cornell University functions fulfilled by peroxisomes, PBD pathology is complex and incompletely understood. Received: Aug 30, 2017 Besides accumulation of peroxisomal educts (like very-long-chain fatty acids [VLCFAs] or Revised: Dec 11, 2017 branched-chain fatty acids) and lack of products (like bile acids or plasmalogens), many per- Accepted: Dec 13, 2017 oxisomal defects lead to detrimental mitochondrial abnormalities for unknown reasons. We generated Pex19 Drosophila mutants, which recapitulate the hallmarks of PBDs, like absence of peroxisomes, reduced viability, neurodegeneration, mitochondrial abnormalities, and ac- cumulation of VLCFAs. We present a model of hepatocyte nuclear factor 4 (Hnf4)-induced lipotoxicity and accumulation of free fatty acids as the cause for mitochondrial damage in consequence of peroxisome loss in Pex19 mutants. Hyperactive Hnf4 signaling leads to up- regulation of lipase 3 and enzymes for mitochondrial β-oxidation.
    [Show full text]
  • Catecholamine-Induced Lipolysis in Obesity
    International Journal of Obesity (1999) 23, Suppl 1, 10±13 ß 1999 Stockton Press All rights reserved 0307±0565/99 $12.00 http://www.stockton-press.co.uk/ijo Catecholamine-induced lipolysis in obesity Peter Arner1* 1Department of Medicine, Karolinska Institute at Huddinge University Hospital, CME, S-141 86 Huddinge, Sweden Catecholamines are the only hormones with pronounced lipolytic action in man. A number of in vivo and in vitro studies suggest that there is lipolytic resistance to catecholamines in subcutaneous adipose tissue, which is the major fat depot in obese subjects. This is due to multiple alterations in catecholamine signal transduction, involving decreased expression and function of b2-adrenoceptors, increased function of a2-adrenoceptors and decreased ability of cyclic monophosphate (AMP) to stimulate hormone sensitive lipase. A sedentary life-style, which usually characterizes obesity, may contribute to the catecholamine resistance. However, hereditary=genetic factors may also be involved. Recently, decreased expression and function of hormone sensitive lipase has been found in subcutaneous adipocytes of non-obese subjects with heredity for obesity. In addition, polymorphisms in the genes for b2-adrenoceptors, b3-adrenoceptors and hormone sensitive lipase, associate with obesity. On the other hand, catecholamine-induced lipolysis in visceral adipose tissue is increased in obesity due to increased function of b3- adrenoceptors (major ®nding), decreased function of a2-adrenoceptors and increased ability of cyclic AMP to stimulate lipolysis. When the ®ndings in different adipose regions are considered together, it appears that there is a re- distribution of lipolysis and thereby fatty acid mobilization in obesity, favouring the visceral fat depot.
    [Show full text]
  • Increased Lipolysis and Its Consequences On
    Increased Lipolysis and Its Consequences on Gluconeogenesis in Non-insulin-dependent Diabetes Mellitus Nurjahan Nurjhan, Agostino Consoli, and John Gerich Clinical Research Center, Departments ofMedicine and Physiology, University ofPittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261 Abstract version to glucose (2-4). Although - 50% ofthe glycerol that is The present studies were undertaken to determine whether Ii- released into plasma in the postabsorptive state is converted to polysis was increased in non-insulin-dependent diabetes melli- glucose (3-5), glycerol is normally considered a minor gluco- tus (NIDDM) and, if so, to assess the influence of increased neogenic substrate since it accounts for only - 3% of overall glycerol availability on its conversion to glucose and its contri- hepatic glucose output and 10% of overall gluconeogenesis (3, bution to the increased gluconeogenesis found in this condition. 4). After a prolonged fast, however, lipolysis greatly increases For this purpose, we infused nine subjects with NIDDM and 16 and the proportion of glycerol turnover used for gluconeogene- sis also increases so that glycerol can account for up to 60% of age-, weight-matched nondiabetic volunteers with 12-3H1 glu- overall cose and IU-'4C1 glycerol and measured their rates of glucose hepatic glucose output (3). and glycerol appearance in plasma and their rates of glycerol In non-insulin-dependent diabetes mellitus (NIDDM),' incorporation into plasma glucose. The rate of glycerol appear- overall gluconeogenesis is increased (6), and recently enhanced ance, an index of lipolysis, was increased 1.5-fold in NIDDM conversion of both lactate and alanine to glucose has been re- vs. ported (7).
    [Show full text]
  • Regulation of Ketone Body and Coenzyme a Metabolism in Liver
    REGULATION OF KETONE BODY AND COENZYME A METABOLISM IN LIVER by SHUANG DENG Submitted in partial fulfillment of the requirements For the Degree of Doctor of Philosophy Dissertation Adviser: Henri Brunengraber, M.D., Ph.D. Department of Nutrition CASE WESTERN RESERVE UNIVERSITY August, 2011 SCHOOL OF GRADUATE STUDIES We hereby approve the thesis/dissertation of __________________ Shuang Deng ____________ _ _ candidate for the ________________________________degree Doctor of Philosophy *. (signed) ________________________________________________ Edith Lerner, PhD (chair of the committee) ________________________________________________ Henri Brunengraber, MD, PhD ________________________________________________ Colleen Croniger, PhD ________________________________________________ Paul Ernsberger, PhD ________________________________________________ Janos Kerner, PhD ________________________________________________ Michelle Puchowicz, PhD (date) _______________________June 23, 2011 *We also certify that written approval has been obtained for any proprietary material contained therein. I dedicate this work to my parents, my son and my husband TABLE OF CONTENTS Table of Contents…………………………………………………………………. iv List of Tables………………………………………………………………………. viii List of Figures……………………………………………………………………… ix Acknowledgements………………………………………………………………. xii List of Abbreviations………………………………………………………………. xiv Abstract…………………………………………………………………………….. xvii CHAPTER 1: KETONE BODY METABOLISM 1.1 Overview……………………………………………………………………….. 1 1.1.1 General introduction
    [Show full text]
  • Lipolysis, Β-Oxidation & Ketone Body Formation
    Lipolysis, β-oxidation & ketone body formation Craig Wheelock February 1st, 2008 Questions? Comments? [email protected] Catabolism’s 3 stages Lipolysis β-oxidation Catabolism is the set of metabolic pathways that break down molecules into smaller units & release energy Catabolism’s 3 stages • Stage 1 – food is broken down into smaller units - digestion • Stage 2 – these molecules are degraded to simple units that play a central role in metabolism • Stage 3 – ATP is produced from the complete oxidation of the acetyl unit of acetyl CoA Lipids to be degraded come from 2 sources: a) Food b) Fat deposits - adults eat (adipocytes) 60-150 g/day ->90% TAG the rest: cholesterol, cholesterol esters, PL, FA...... a) Pancreas lipases break down TAG to FFA and 2-MAG Cholesterol esters are hydrolyzed to cholesterol and FFAs FAs are cleaved from PLs Phospholipases Dietary lipids are transported in chylomicrons Lipoprotein transport particles (TAGs and apoliprotein B-48) Blood process repeats itself in reverse Membrane-bound lipases degrade TGs to FFAs and MAGs for transport into tissue . Chylomicron •large lipoprotein particles (diameter of 75 to 1,200 nm) •created by the absorptive cells of the small intestine •composed of TAGs (85%) & contain some cholesterol & cholesteryl esters b) Stored fat as an energy source Energy depots • Glycogen in muscle – 1200 kcal • Glycogen in liver – 400 kcal • Triacylglycerols in fat – 135,000 kcal • Proteins (mainly muscle) – 24,000 kcal Mobilization of stored fat: a hormone sensitive lipase hydrolyzes TAG to FFA
    [Show full text]
  • Modulation of Lipolysis and Glycolysis Pathways in Cancer Stem Cells Changed Multipotentiality and Differentiation Capacity Towa
    Pouyafar et al. Cell Biosci (2019) 9:30 https://doi.org/10.1186/s13578-019-0293-z Cell & Bioscience LETTER TO THE EDITOR Open Access Modulation of lipolysis and glycolysis pathways in cancer stem cells changed multipotentiality and diferentiation capacity toward endothelial lineage Ayda Pouyafar1, Milad Zadi Heydarabad1, Jalal Abdolalizadeh2, Reza Rahbarghazi2,3*† and Mehdi Talebi2*† Abstract Cancer stem cells obtain energy demand through the activation of glycolysis and lipolysis. It seems that the use of approached targeting glycolysis and lipolysis could be an efective strategy for the inhibition of cancer stem cells. In the current experiment, we studied the potential efect of glycolysis and lipolysis inhibition on cancer stem cells diferentiation and mesenchymal–epithelial-transition capacity. Cancer stem cells were enriched from human ovarian cells namely SKOV3 by using MACS technique. Cells were exposed to Lonidamine, an inhibitor of glycolysis, and TOFA, a potent inhibitor of lipolysis for 7 days in endothelial diferentiation medium; EGM-2 and cell viability was studied by MTT assay. At the respective time point, the transcription level of genes participating in EMT such as Zeb-1, -2, Vimen- tin, Snail-1, -2 and VE-cadherin were measured by real-time PCR analysis. Our data noted that the inhibition of lipolysis and glycolysis could decrease cell viability compared to the control of cancer stem cells. The inhibition of glycolysis prohibited the expression of Zeb-1, Snails, and Vimentin while increased endothelial diferentiation rate indicated by the expression of VE-cadherin. In contrast, the inhibition of lipolysis increased EMT associated genes and reduced endothelial diferentiation rate by suppressing the transcription of VE-cadherin.
    [Show full text]
  • Adropin Slightly Modulates Lipolysis, Lipogenesis and Expression of Adipokines but Not Glucose Uptake in Rodent Adipocytes
    G C A T T A C G G C A T genes Article Adropin Slightly Modulates Lipolysis, Lipogenesis and Expression of Adipokines but Not Glucose Uptake in Rodent Adipocytes Mariami Jasaszwili 1, Ewa Pruszy ´nska-Oszmałek 1 , Tatiana Wojciechowicz 1 , Mathias Z. Strowski 2,3 , Krzysztof W. Nowak 1 and Marek Skrzypski 1,* 1 Department of Animal Physiology, Biochemistry and Biostructure, Poznan University of Life Sciences, 60-637 Poznan, Poland; [email protected] (M.J.); [email protected] (E.P.-O.); [email protected] (T.W.); [email protected] (K.W.N.) 2 Department of Hepatology and Gastroenterology, Charité-University Medicine Berlin, 13353 Berlin, Germany; [email protected] 3 Department of Internal Medicine-Gastroenterology & Oncology, Park-Klinik Weissensee, 13086 Berlin, Germany * Correspondence: [email protected]; Tel.: +48-618-486-137; Fax: +48-618-487-197 Abstract: Adropin is a peptide hormone which modulates energy homeostasis and metabolism. In animals with diet-induced obesity, adropin attenuates adiposity and improves lipid and glucose homeostasis. Adropin promotes the proliferation of rodent white preadipocytes and suppresses their differentiation into adipocytes. By contrast, the effects of adropin on mature white adipocytes are unknown. Therefore, we aimed to evaluate the effects of adropin on lipolysis, lipogenesis Citation: Jasaszwili, M.; and glucose uptake in white rodent adipocytes. We assessed the effects of adropin on the mRNA Pruszy´nska-Oszmałek,E.; expression of adiponectin, resistin and visfatin. White preadipocytes were isolated from male Wistar Wojciechowicz, T.; Strowski, M.Z.; rats. Differentiated 3T3-L1 cells were used as a surrogate model of white adipocytes.
    [Show full text]