Abdominal Obesity and Cardiovascular Disease
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Obesity and Reproduction: a Committee Opinion
Obesity and reproduction: a committee opinion Practice Committee of the American Society for Reproductive Medicine American Society for Reproductive Medicine, Birmingham, Alabama The purpose of this ASRM Practice Committee report is to provide clinicians with principles and strategies for the evaluation and treatment of couples with infertility associated with obesity. This revised document replaces the Practice Committee document titled, ‘‘Obesity and reproduction: an educational bulletin,’’ last published in 2008 (Fertil Steril 2008;90:S21–9). (Fertil SterilÒ 2015;104:1116–26. Ó2015 Use your smartphone by American Society for Reproductive Medicine.) to scan this QR code Earn online CME credit related to this document at www.asrm.org/elearn and connect to the discussion forum for Discuss: You can discuss this article with its authors and with other ASRM members at http:// this article now.* fertstertforum.com/asrmpraccom-obesity-reproduction/ * Download a free QR code scanner by searching for “QR scanner” in your smartphone’s app store or app marketplace. he prevalence of obesity as a exceed $200 billion (7). This populations have a genetically higher worldwide epidemic has underestimates the economic burden percent body fat than Caucasians, T increased dramatically over the of obesity, since maternal morbidity resulting in greater risks of developing past two decades. In the United States and adverse perinatal outcomes add diabetes and CVD at a lower BMI of alone, almost two thirds of women additional costs. The problem of obesity 23–25 kg/m2 (12). and three fourths of men are overweight is also exacerbated by only one third of Known associations with metabolic or obese, as are nearly 50% of women of obese patients receiving advice from disease and death from CVD include reproductive age and 17% of their health-care providers regarding weight BMI (J-shaped association), increased children ages 2–19 years (1–3). -
Metabolic Syndrome: Past, Present and Future
nutrients Editorial Metabolic Syndrome: Past, Present and Future Isabelle Lemieux 1,* and Jean-Pierre Després 1,2,3 1 Centre de recherche de l’Institut universitaire de cardiologie et de pneumologie de Québec—Université Laval, Québec, QC G1V 4G5, Canada; [email protected] 2 Department of Kinesiology, Faculty of Medicine, Université Laval, Québec, QC G1V 0A6, Canada 3 VITAM—Centre de recherche en santé durable, CIUSSS de la Capitale-Nationale, Québec, QC G1J 0A4, Canada * Correspondence: [email protected]; Tel.: +1-418-656-8711 (ext. 3603) Received: 28 October 2020; Accepted: 29 October 2020; Published: 14 November 2020 1. Syndrome X: A Tribute to a Pioneer, Gerald M. Reaven Most clinicians and health professionals have heard or read about metabolic syndrome. For instance, as of October 2020, entering “metabolic syndrome” in a PubMed search generated more than 57,000 publications since the introduction of the concept by Grundy and colleagues in 2001 [1]. Although many health professionals are familiar with the five criteria proposed by the National Cholesterol Education Program-Adult Treatment Panel III for its diagnosis (waist circumference, triglycerides, high-density lipoprotein (HDL) cholesterol, blood pressure and glucose), how these variables were selected and the rationale used for the identification of cut-offs remain unclear for many people. In addition, the conceptual definition of metabolic syndrome is often confused with the tools (the five criteria) that have been proposed to make its diagnosis [2,3]. In the seminal paper of his American Diabetes Association 1988 Banting award lecture, Reaven put forward the notion that insulin resistance was not only a fundamental defect increasing the risk of type 2 diabetes, but he also proposed that it was a prevalent cause of cardiovascular disease [4]. -
Vascular Metabolic Dysfunction and Lipotoxicity
Physiol. Res. 56: 149-158, 2007 Vascular Metabolic Dysfunction and Lipotoxicity H. M. MATTERN, C. D. HARDIN Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO, USA Received November 10, 2005 Accepted March 7, 2006 On-line available March 23, 2006 Summary The purpose of this study was to determine the role of lipotoxicity in vascular smooth muscle (VSM). C1-BODIPY 500/510 C12 used to assess the ability of VSM A7r5 cells to transport long-chain fatty acids showed that lipid transport did not appear to limit metabolism. Thin layer chromatography revealed that storage of transported fatty acid occurred primarily as mono- and diglycerides and fatty acids but not as triglycerides. We used lipid-induced apoptosis as a measure of lipotoxicity and found that 1.5 mM palmitate (6.8:1) bound to albumin resulted in a 15-fold increase in the number of apoptotic cells compared to the control at 24 hours. This apoptosis did not seem to be due to an increase in reactive oxygen species (ROS) since VSM cells incubated in palmitate showed less ROS production than cells incubated in albumin only. Similar exposure to oleate did not significantly increase the number of apoptotic cells compared to the control. Oleate actually significantly attenuated the apoptosis induced by palmitate, suggesting that unsaturated fatty acids have a protective effect on cells undergoing palmitate-induced apoptosis. These results suggest that vascular smooth muscle is vulnerable to lipotoxicity and that this lipotoxicity may play a role in the development of atherosclerosis. Key words Vascular smooth muscle • Palmitate • Oleate • Apoptosis • Reactive oxygen species Introduction Geng and Libby 2002). -
Skeletal Muscle Lipotoxicity in Insulin Resistance and Type 2 Diabetes: a Causal Mechanism Or an Innocent Bystander?
176:2 C Brøns and L G Grunnet Dysfunctional adipose tissue 176:2 R67–R78 Review and T2D MECHANISMSPROOF IN ENDOCRINOLOGY ONLY Skeletal muscle lipotoxicity in insulin resistance and type 2 diabetes: a causal mechanism or an innocent bystander? Charlotte Brøns and Louise Groth Grunnet Correspondence should be addressed Department of Endocrinology (Diabetes and Metabolism), Rigshospitalet, Copenhagen, Denmark to C Brøns Email [email protected] Abstract Dysfunctional adipose tissue is associated with an increased risk of developing type 2 diabetes (T2D). One characteristic of a dysfunctional adipose tissue is the reduced expandability of the subcutaneous adipose tissue leading to ectopic storage of fat in organs and/or tissues involved in the pathogenesis of T2D that can cause lipotoxicity. Accumulation of lipids in the skeletal muscle is associated with insulin resistance, but the majority of previous studies do not prove any causality. Most studies agree that it is not the intramuscular lipids per se that causes insulin resistance, but rather lipid intermediates such as diacylglycerols, fatty acyl-CoAs and ceramides and that it is the localization, composition and turnover of these intermediates that play an important role in the development of insulin resistance and T2D. Adipose tissue is a more active tissue than previously thought, and future research should thus aim at examining the exact role of lipid composition, cellular localization and the dynamics of lipid turnover on the development of insulin resistance. In addition, ectopic storage of fat has differential impact on various organs in different phenotypes at risk of developing T2D; thus, understanding how adipogenesis is regulated, the interference European Journal European of Endocrinology with metabolic outcomes and what determines the capacity of adipose tissue expandability in distinct population groups is necessary. -
Impact of Fat Mass and Distribution on Lipid Turnover in Human Adipose Tissue
Impact of fat mass and distribution on lipid turnover in human adipose tissue Kirsty Spalding, Samuel Bernard, Erik Näslund, Mehran Salehpour, Göran Possnert, Lena Appelsved, Keng-Yeh Fu, Kanar Alkass, Henrik Druid, Anders Thorell, et al. To cite this version: Kirsty Spalding, Samuel Bernard, Erik Näslund, Mehran Salehpour, Göran Possnert, et al.. Impact of fat mass and distribution on lipid turnover in human adipose tissue. Nature Communications, Nature Publishing Group, 2017, 8, pp.15253. 10.1038/ncomms15253. hal-01561605 HAL Id: hal-01561605 https://hal.archives-ouvertes.fr/hal-01561605 Submitted on 13 Jul 2017 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. ARTICLE Received 17 Aug 2016 | Accepted 13 Mar 2017 | Published 23 May 2017 DOI: 10.1038/ncomms15253 OPEN Impact of fat mass and distribution on lipid turnover in human adipose tissue Kirsty L. Spalding1,2, Samuel Bernard3, Erik Na¨slund4, Mehran Salehpour5,Go¨ran Possnert5, Lena Appelsved1, Keng-Yeh Fu1, Kanar Alkass1, Henrik Druid6,7, Anders Thorell4,8, Mikael Ryde´n9 & Peter Arner9 Differences in white adipose tissue (WAT) lipid turnover between the visceral (vWAT) and subcutaneous (sWAT) depots may cause metabolic complications in obesity. -
Ceramides: Nutrient Signals That Drive Hepatosteatosis
J Lipid Atheroscler. 2020 Jan;9(1):50-65 Journal of https://doi.org/10.12997/jla.2020.9.1.50 Lipid and pISSN 2287-2892·eISSN 2288-2561 Atherosclerosis Review Ceramides: Nutrient Signals that Drive Hepatosteatosis Scott A. Summers Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, UT, USA Received: Sep 24, 2019 ABSTRACT Revised: Nov 4, 2019 Accepted: Nov 10, 2019 Ceramides are minor components of the hepatic lipidome that have major effects on liver Correspondence to function. These products of lipid and protein metabolism accumulate when the energy needs Scott A. Summers of the hepatocyte have been met and its storage capacity is full, such that free fatty acids start Department of Nutrition and Integrative to couple to the sphingoid backbone rather than the glycerol moiety that is the scaffold for Physiology, University of Utah, 15N 2030E, Salt Lake City, UT 84112, USA. glycerolipids (e.g., triglycerides) or the carnitine moiety that shunts them into mitochondria. E-mail: [email protected] As ceramides accrue, they initiate actions that protect cells from acute increases in detergent- like fatty acids; for example, they alter cellular substrate preference from glucose to lipids Copyright © 2020 The Korean Society of Lipid and they enhance triglyceride storage. When prolonged, these ceramide actions cause insulin and Atherosclerosis. This is an Open Access article distributed resistance and hepatic steatosis, 2 of the underlying drivers of cardiometabolic diseases. under the terms of the Creative Commons Herein the author discusses the mechanisms linking ceramides to the development of insulin Attribution Non-Commercial License (https:// resistance, hepatosteatosis and resultant cardiometabolic disorders. -
The Obesity Paradox: a Statistical Outcome Or a Real Effect of Clinical Relevance?
Review J Hypertens Res (2019) 5(4):162–166 The obesity paradox: a statistical outcome or a real effect of clinical relevance? Ivona Mitu1, Cristina Daniela Dimitriu2, O. Mitu3*, Manuela Ciocoiu4 1“Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania, 2Department of Morpho-Functional Sciences (II), “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania 3Department of Medical Specialties (I), “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania 4Department of Morpho-Functional Sciences (II), “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania Received: October 10, 2019, Accepted: November 21, 2019 Abstract Obesity is one of the most important risk factors for morbidity and mortality, especially when referring to car- diovascular diseases. Different obesity phenotypes are presented in the medical literature, each one describing a different cardiovascular risk profile. The most important phenotype that is directly linked to the obesity paradox (OP) is the metabolically healthy obese phenotype, characterizing individuals with a BMI ≥ 30 kg/m2 and no metabolic abnormalities. This phenotype strengthens the true existence of the OP. In the same time we need to consider all the possible influencers when concluding if the OP is real and worth taking into consideration by clinicians. Analyzing studies that mention the OP, we observed several limitations either of the study itself or of the BMI used to classify obese patients. These limitations are described in the present review and they are of great importance in understanding how the OP is defined and how it should be interpreted. Keywords: obesity paradox, cardiovascular, BMI, obesity phenotypes. Introduction that the obesity prevalence has doubled since 1980, reaching 5% in children and 12% in adults [1]. -
Apolipoprotein O Is Mitochondrial and Promotes Lipotoxicity in Heart
Apolipoprotein O is mitochondrial and promotes lipotoxicity in heart Annie Turkieh, … , Philippe Rouet, Fatima Smih J Clin Invest. 2014;124(5):2277-2286. https://doi.org/10.1172/JCI74668. Research Article Cardiology Diabetic cardiomyopathy is a secondary complication of diabetes with an unclear etiology. Based on a functional genomic evaluation of obesity-associated cardiac gene expression, we previously identified and cloned the gene encoding apolipoprotein O (APOO), which is overexpressed in hearts from diabetic patients. Here, we generated APOO-Tg mice, transgenic mouse lines that expresses physiological levels of human APOO in heart tissue. APOO-Tg mice fed a high-fat diet exhibited depressed ventricular function with reduced fractional shortening and ejection fraction, and myocardial sections from APOO-Tg mice revealed mitochondrial degenerative changes. In vivo fluorescent labeling and subcellular fractionation revealed that APOO localizes with mitochondria. Furthermore, APOO enhanced mitochondrial uncoupling and respiration, both of which were reduced by deletion of the N-terminus and by targeted knockdown of APOO. Consequently, fatty acid metabolism and ROS production were enhanced, leading to increased AMPK phosphorylation and Ppara and Pgc1a expression. Finally, we demonstrated that the APOO-induced cascade of events generates a mitochondrial metabolic sink whereby accumulation of lipotoxic byproducts leads to lipoapoptosis, loss of cardiac cells, and cardiomyopathy, mimicking the diabetic heart–associated metabolic phenotypes. -
How Strong Is the Association Between Abdominal Obesity and the Incidence of Type 2 Diabetes? International Journal of Clinical Practice, Volume 62 (Number 9)
Original citation: Freemantle, Nick, Holmes, J. (Jeremy), Hockey, A. and Kumar, Sudhesh. (2008) How strong is the association between abdominal obesity and the incidence of type 2 diabetes? International Journal of Clinical Practice, Volume 62 (Number 9). pp. 1391- 1396. Permanent WRAP url: http://wrap.warwick.ac.uk/29585 Copyright and reuse: The Warwick Research Archive Portal (WRAP) makes this work of researchers of the University of Warwick available open access under the following conditions. This article is made available under the Creative Commons Attribution- 2.5 Unported (CC BY NC 2.5) license and may be reused according to the conditions of the license. For more details see http://creativecommons.org/licenses/by-nc/2.5/ A note on versions: The version presented in WRAP is the published version, or, version of record, and may be cited as it appears here. For more information, please contact the WRAP Team at: [email protected] http://wrap.warwick.ac.uk/ doi: 10.1111/j.1742-1241.2008.01805.x META-ANALYSIS How strong is the association between abdominal obesity and the incidence of type 2 diabetes? N. Freemantle,1 J. Holmes,2 A. Hockey,3 S. Kumar4 OnlineOpen: This article is available free online at www.blackwell-synergy.com SUMMARY 1School of Primary Care, Review Criteria Occupational and Public Health, Background: Quantitative evidence on the strength of the association between • Comprehensive searches of Medline and Embase University of Birmingham, abdominal obesity and the incidence of type 2 diabetes was assessed. Methods: undertaken in March 2006. Exclusion criteria Birmingham, UK 2 Systematic review of longitudinal studies assessing the relationship between mea- agreed by authors. -
Obesity, Diabetes and Longevity in the Gulf: Is There a Gulf Metabolic Syndrome?
Obesity, diabetes and longevity in the Gulf: is there a Gulf Metabolic Syndrome? Article Published Version Open Access Guy, G. W., Nunn, A. V.W., Thomas, L. E. and Bell, J. D. (2009) Obesity, diabetes and longevity in the Gulf: is there a Gulf Metabolic Syndrome? International Journal of Diabetes Mellitus, 1 (1). pp. 43-54. ISSN 1877-5934 doi: https://doi.org/10.1016/j.ijdm.2009.05.001 Available at http://centaur.reading.ac.uk/35380/ It is advisable to refer to the publisher’s version if you intend to cite from the work. See Guidance on citing . To link to this article DOI: http://dx.doi.org/10.1016/j.ijdm.2009.05.001 Publisher: Elsevier All outputs in CentAUR are protected by Intellectual Property Rights law, including copyright law. Copyright and IPR is retained by the creators or other copyright holders. Terms and conditions for use of this material are defined in the End User Agreement . www.reading.ac.uk/centaur CentAUR Central Archive at the University of Reading Reading’s research outputs online This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues. Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. -
Chapter 8 Abdominal Obesity and the Metabolic Syndrome
Chapter 8 Abdominal Obesity and the Metabolic Syndrome Jean-Pierre Desprésa,b, Isabelle Lemieuxa and Natalie Almérasc aQuébec Heart Institute, Hôpital Laval Research Center, Hôpital Laval, Québec, Québec, Canada bDepartment of Social and Preventive Medicine, Université Laval, Québec, Québec, Canada cHôpital Laval Research Center, Hôpital Laval, Québec, Québec, Canada 1. INTRODUCTION Despite the fact that the obesity epidemic has received intense media cover- age, many physicians still fail to recognize that the rapidly growing prevalence of type 2 diabetes in their practice is the result of our “toxic” sedentary and affluent lifestyle that promotes weight gain, obesity, a positive energy balance, and the progressive development of a dysmetabolic state [1], potentially lead- ing to glucose intolerance and—eventually—outright hyperglycemia. Citing obesity’s key role in the etiology of type 2 diabetes, Zimmet foresaw a rapid increase in the prevalence of type 2 diabetes worldwide [2, 3]. Unfortunately, the progression of obesity has been so brisk that the worldwide prevalence of type 2 diabetes continues to grow at an alarming rate. This phenomenon should be of great concern to health care providers, as type 2 diabetes has been clearly linked to major health care expenses [4]. Indeed, it is a major cause of retinopa- thy causing blindness, of nephropathy leading to end-stage renal disease and dialysis, as well as of neuropathic complications, which are the leading cause of amputations [5]. In addition to the microcirculatory damage it causes, type 2 diabetes also plays a key role in atherosclerotic macrovascular disease. For in- stance, the majority of type 2 diabetic patients will die from cardiovascular disease [6–8]. -
Understanding and Diagnosing Hyperinsulinaemia Catherine Crofts
Understanding and Diagnosing Hyperinsulinaemia Catherine Crofts A thesis submitted to AUT University in fulfilment of the requirements for the degree of Doctor of Philosophy 2015 Human Potential Centre Primary Supervisor: Grant Schofield Secondary Supervisor: Caryn Zinn Tertiary Supervisor: Mark Wheldon Abstract Traditionally, insulin resistance is thought to be the precursor to many metabolic diseases. It is now believed that compensatory hyperinsulinaemia, previously thought to be a symptom of insulin resistance, may independently associated with metabolic disease and have its own pathological implications. Further understanding of compensatory hyperinsulinaemia may offer new insights into the aetiology of metabolic disease. This thesis provides novel work in hyperinsulinaemia and is broadly divided into four parts. Part 1 comprises a collation of the literature to show the aetiology and pathologies of hyperinsulinaemia, and to critically review the current diagnostic methods. The aetiology of hyperinsulinaemia is not yet fully elucidated, but is likely to include excessive carbohydrate ingestion, excessive cortisol or uric acid production, and/or medications. Subsequent pathologies include: cardio-, cerebro-, and peripheral- vascular disorders; type 2 diabetes; inflammation; and certain cancers or dementias. This is the first review to comprehensively link hyperinsulinaemia to such a wide range of metabolic disorders. Except for fasting insulin levels being considered unreliable, there was no consensus regarding diagnostic criteria. This means that diagnostic criteria needs to be determined prior to further research. Part 2 examined the prevalence of hyperinsulinaemia in the Kraft database. This important database comprises a large sample of oral glucose tolerance tests with insulin assays collected over 20 years in Chicago, USA. From the 15 000 available tests, those involving men aged ≥ 20 years and women ≥ 45 years, with a BMI > 18kg/m2 were included (n = 7750).