Ebook Obesity-A practical guide: Part 1

Shamim I. Ahmad
Syed Khalid Imam
Editors

Obesity
A Practical Guide

123


Obesity



Shamim I. Ahmad • Syed Khalid Imam
Editors

Obesity
A Practical Guide


Editors
Shamim I. Ahmad
School of Science and Technology
Nottingham Trent University
Nottingham, UK

Syed Khalid Imam
Al Mouwasat Hospital
Jubail, Saudi Arabia

ISBN 978-3-319-19820-0
ISBN 978-3-319-19821-7
DOI 10.1007/978-3-319-19821-7

(eBook)

Library of Congress Control Number: 2015954076
Springer Cham Heidelberg New York Dordrecht London
© Springer International Publishing Switzerland 2016
This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or
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exempt from the relevant protective laws and regulations and therefore free for general use.
The publisher, the authors and the editors are safe to assume that the advice and information in
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Printed on acid-free paper
Springer International Publishing AG Switzerland is part of Springer Science+Business Media
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The editor (SIA) wishes to dedicate this book to his wife Riasat
Jan for her patience, love and persistent encouragement during
the production of this book and to his children, Alisha Ahmad
and Arsalan Mujtaba Ahmad, who have been giving him so

much pleasure with their innocent interceptions and resulting
recovery from the loss of energy. Also dedication goes to those
obese subjects, who may not be fully aware about the
seriousness of this disease and hence may be suffering from
various complications and bravely fighting them. Also to the
caregivers, nurses and medics who painstakingly look after
them throughout their suffering period.
The editor (SKI) wishes to dedicate this book to his parents,
Ahmad Imam and Mah Jabeen, for their constant support,
patronage and guidance in his career; his children, Abdullah,
Maham and Ebadullah, whose voices and gestures were never
boring and from them he has learned a love and enjoyed
flavour of life; his wife, Uzma, the key family member, who
lifted his heart and encouraged him a lot because of her
spiritual wholeness, inexhaustible hope and strong personality.
Lastly, to all patients who have been suffering from various
kind of illnesses and fight against the ailment with great
courage and hope.



Preface

Although obesity is an age-old problem, existing probably ever since the
humans came into existence, recent studies show that this problem is on
increase with an alarming rate, especially in the industrialised and affluent
countries. The reasons put forward for this increase include the life style,
over-eating, consumption of commercially processed food especially with
high-caloric value and high levels of sugar and fat, addiction for fast food,
lack of exercise and sedentary life style. Also genetic makeup has been associated with the obesity.

It is estimated that currently in industrialised countries, about 20–40 % of
the population is obese and by 2030, if the trend will continue, this may
increase up to 50 %. Current studies show that in the USA around 1 in 3
persons is obese, and by 2040 it is predicted that obesity in most industrialised and oil producing countries may reach to the pandemic level if no
serious control measures are taken.
We do not know when the word obesity was coined but whenever was, it
was defined as a condition and a manifestation of consumer society. In 2007,
the World Health Organization (WHO) has recognised obesity as a disease,
and the recognition is mainly based on several important developments
including epidemiological data, progress in pathological concept and increase
in health expenditure due to obesity, as well as obesity-associated health
problems.
In the past, obesity was considered to be a disease of the middle- to
late-aged groups of the people, but in the last one or two decades, obesity
among children has been increasing with an alarming rate. Sedentary life
style and consumption of high amount of sugar and fast food may be the two
most important reasons for this increase. Interestingly in a recent research
report, it has been shown that in developing countries such as in Middle East
and North Africa, the gender difference in obesity is prevailing, in that there
are more obese women than men. Several reasons including consumption of
food, laden with sugar, among women is greater there. Also the cultural
values favouring larger body size among women is considered as a sign of
fertility; healthfulness and prosperity are the additional reasons for increased
obesity in women than men.
Obesity on its own is not a lethal disease, but it can give rise to a number
of lethal and non-lethal ailments. Coronary heart disease and stroke, dyslipidemia contributing to a number of metabolic syndromes, high blood pressure and hypertension, certain cancers and insulin resistance in diabetes are
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some of the important examples. These diseases account to highest number of
human death amongst all other causes. Amongst non-lethal conditions are
included osteoarthritis, pancreatitis, diseases of digestive organs, sleep
apnoea, gout, asthma, dementia, increased stress, loss of intelligentsia, effect
on human sexual development, difficulty in management in pregnancy and
premature birth. Chronic and low-grade inflammation is also associated with
obesity due to high-level accumulation of adipose tissue. In other words, obesity not only can lead to premature death but the quality of life of the obese
people, for various reasons, may be significantly less pleasurable than their
counterpart with normal body weight. Whereas, at present, little can be done
if obesity is due to genetic makeup such as a reduction in brown adipose tissue, for other reasons effective measures are required to be taken to eradicate
or at least reduce obesity. If not, the prediction is that the disease soon may
reach to the pandemic levels.
In recent years, media have been playing important roles in highlighting
the importance of damage caused by the obesity including premature death;
nevertheless, little or no significant effects can be seen in the population and
the obesity remains on increase, especially amongst children. Hence it is
important that more education, campaign and research are needed to stop this
increasing curse.
The editors believe that obesity is one of the most important health problems of the twenty-first century, yet money spent on obesity research is notoriously low in comparison to those diseases where drug companies can make
substantial profits. If serious measures not taken, as soon as possible, this
disease not only will become a huge burden over the health services but a
huge number of population will suffer due to the lack of knowledge. The editors believe that gaining knowledge about obesity is indeed a treatment.
Although the CONTENTS in the book do not show the chapters
sectionalized, it may not be inappropriate for the reader’s guidance to divide
them in sections.
Section 1 includes the Chaps. 1, 2, 3, 4 and 5 describing the basic biochemistry including enzymes and hormones assisting in driving the biochemical reaction, functional impairment, the consequences and the
pathophysiology of obesity. Emphasis has been given on hormones playing
key roles in obesity such as white and brown adipose tissues, long-chain
omega-3 polyunsaturated fatty acids, and leptin. These have been addressed

employing up-to-date research data for the readers to fill any gap left in their
knowledge.
Section 2 includes genetic aspects of obesity and the oxidative stress
which play equally important roles in determining the diseases as well other
syndromes (as shown above).
Section 3 embraces the consequences of obesity which includes fatal diseases leading to premature deaths such as coronary heart disease and diabetes. Among non-fatal syndromes, include sleep apnoea, gastroesophageal
reflux disease, and gastrointestinal disorder in children which may be taken
relatively easily in the medical field. Other consequences of obesity include
non-alcoholic fatty liver disease and chronic kidney disease, which can
become fatal and require more research. Polycystic ovary syndrome develop-

Preface


Preface

ix

ing due to obesity is another medical condition usually leading to infertility.
Obesity can also lead to certain types of cancer including thyroid cancer
which has been described in detail in this book. A non-fatal but equally
important effect of obesity is suffering from depression. This is another
important consequence of obesity, and guidance has been provided in the
chapter on how to handle this syndrome.
Section 4 explains the technologies available in the assessment and treatment of obesity including orthopaedic and trauma surgery, obstetrical risk in
obesity and bariatric surgery including its underlying physiological mechanisms. Surgeons specialised in the field have been participating to update the
readers from the current technology and most popular methods employed in
the processes.
Section 5 covers another set of important subject associated with obesity,
namely, the infant nutrition, their caloric importance and the formulae which

can contribute towards the development of obesity. The section also discuss
the roles of eating disorders, specially consumption of high- calorie food and
sugar enriched drinks, plays in obesity.
Nottingham, UK
Jubail, Saudi, Arabia

Shamim I. Ahmad
Syed Khalid Imam



Acknowledgement

The editors cordially acknowledge the various authors of this book for their
contribution of the chapters with in-depth knowledge and highly skilled
presentation. Without their input, it would not have been possible to produce
this book on such an important subject and common endocrine dysfunction.
We would also like to acknowledge the hard work, friendly approach and
patience of the staff, especially of Ms Julia Megginson, of Springer
Publications for efficient and highly professional handling of this project.

xi



About the Editors

Shamim I Ahmad after obtaining his Master’s degree in botany from Patna
University, Bihar, India, and his PhD in Molecular Genetics from Leicester
University, England, joined Nottingham Polytechnic as grade 1 lecturer and

subsequently promoted to SL post. Nottingham Polytechnic subsequently
became Nottingham Trent University where after serving for about 35 years,
he took early retirement yet still serving as a part-time lecturer. He is now
spending much of his time producing/writing medical books. For more than
three decades he researched on different areas of molecular biology/genetics
including thymineless death in bacteria, genetic control of nucleotide catabolism, development of anti-AIDs drug, control of microbial infection of burns,
phages of thermophilic bacteria, and microbial flora of Chernobyl after the
nuclear accident. But his main interest which started about 30 years ago is
DNA damage and repair specifically by near ultraviolet light specially
through the photolysis of biological compounds, production of reactive oxygen species, and their implications on human health including skin cancer. He
is also investigating NUV photolysis of nonbiological compounds such as
8-metoxypsoralen, mitomycin C, and their importance in psoriasis treatment
and in Fanconi anemia. In research collaboration with the University of
Osaka, Japan, he and his co-workers had discovered a number of important
enzymes that play important roles in health and diseases. In 2003, he received
a prestigious “Asian Jewel Award” in Britain for “Excellence in Education”.
He has been editor for the following books published by Landes Bioscience/
Springer publication: Molecular Mechanisms of Fanconi Anemia, Molecular
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Mechanisms of Xeroderma Pigmentosum, Molecular Mechanisms of
Cockayne Syndrome, Molecular Mechanisms of Ataxia Telangiectasia,
Diseases of DNA repair, Neurodegenerative Diseases, and Diabetes: An Old
Disease, a New Insight. Also a co-author for the book Diabetes: A
Comprehensive Treatise for Patients and Caregivers.

Dr. Syed Khalid Imam is an Assistant Professor of Medicine and Consultant

Endocrinologist. He acquired Fellowship in Internal Medicine from College
of Physicians and Surgeons Pakistan (CPSP) and Fellowship in Endocrinology
from American College of Endocrinology (FACE). He was trained as a
Clinical Fellow in Endocrinology at Liaquat National Hospital and Medical
College, Karachi-Pakistan, one of the biggest private tertiary care hospitals of
the country.
He affiliated with the abovementioned institute for more than fifteen years
and accomplished postgraduate training, professional and career growth from
this renowned health care industry. He fulfilled his responsibilities for several
years as Head of Department of Diabetes, Endocrinology and Metabolism,
Program Director of Internal Medicine Residency Training, and Chairman of
Research and Ethics Committee. He is also a supervisor of Endocrinology
Fellowship of CPSP.
He is a member of American Association of Clinical Endocrinologists and
Pakistan Chapter of American Association of Clinical Endocrinologists, an
executive member of Pakistan Endocrine Society, and served as the General
Secretary of the society as well. He also serves as a member of an executive
advisory panel of International Foundation for Mother and Child Health
(IFMCH).
He has published several review articles in national and international journals and participated in many conferences as an invited speaker. Obesity and
diabetes are his areas of special interest and research.

About the Editors


Contents

1

White Adipose Tissue: Beyond Fat Storage . . . . . . . . . . . . . . . . . . 1

Syed Khalid Imam

2

Brown Adipose Tissue and Obesity . . . . . . . . . . . . . . . . . . . . . . . . 13
Gema Jiménez, Elena López-Ruiz, Carmen Griñán-Lisón,
Cristina Antich, and Juan Antonio Marchal

3

Long-Chain Omega-3 Polyunsaturated Fatty Acids
and Obesity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
Mahinda Y. Abeywardena and Damien P. Belobrajdic

4

Leptin and Obesity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
Yuanyuan Zhang and Jun Ren

5

Role of Neuro-Endocrine System in Obesity . . . . . . . . . . . . . . . . 59
Altaf Jawed Baig

6

Oxidative Stress and Obesity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
Isabella Savini, Valeria Gasperi, and Maria Valeria Catani

7

Genetics of Human Obesity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
David Albuquerque, Licínio Manco, and Clévio Nóbrega

8

Obesity and Coronary Heart Disease . . . . . . . . . . . . . . . . . . . . . 107
Helena Tizón-Marcos and Paul Poirier

9

Obesity and Diabetes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117
Shamim I. Ahmad

10

Obesity and Breathing Related Sleep Disorders . . . . . . . . . . . . 131
Antonello Nicolini, Ines M.G. Piroddi, Elena Barbagelata,
and Cornelius Barlascini

11

Gastro-Oesophageal Reflux Disease and Obesity:
Pathophysiology and Putative Treatment . . . . . . . . . . . . . . . . . . 139
Waleed Al-Khyatt and Syed Yousuf Iftikhar

12

Obesity and Gastrointestinal Disorders in Children . . . . . . . . . 149
Uma Padhye Phatak, Madhura Y. Phadke,

and Dinesh S. Pashankar

13

Non-alcoholic Fatty Liver Disease in Obesity. . . . . . . . . . . . . . . 159
Silvia M. Ferolla, Luciana C. Silva,
Claudia A. Couto, and Teresa C.A. Ferrari
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Contents

14

Obesity, Cardiometabolic Risk,
and Chronic Kidney Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181
Samuel Snyder and Natassja Gangeri

15

Polycystic Ovary Syndrome and Obesity . . . . . . . . . . . . . . . . . . 199
Thomas M. Barber, George K. Dimitriadis,
and Stephen Franks

16

Obesity and Cancer. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 211
Xiang Zhang, William K.K. Wu, and Jun Yu

17

Obesity and Thyroid Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . 221
Marjory Alana Marcello, Lucas Leite Cunha,
Fernando De Assis Batista, and Laura Sterian Ward

18

Depression and Obesity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 235
Nina Schweinfurth, Marc Walter, Stefan Borgwardt,
and Undine E. Lang

19

Obesity: Orthopaedics and Trauma Surgery . . . . . . . . . . . . . . . 245
Louis Dagneaux, Sébastien Parratte, Matthieu Ollivier,
and Jean-Noël Argenson

20

New Technology in the Assessment
and Treatment of Obesity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 257
Sofia M. Ramalho, Cátia B. Silva, Ana Pinto-Bastos,
and Eva Conceição

21

Obstetrical Risks in Obesity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 267
Stefania Triunfo

22

Bariatric Surgery in Obesity . . . . . . . . . . . . . . . . . . . . . . . . . . . . 275
Emanuele Lo Menzo, Alex Ordonez,
Samuel Szomstein, and Raul J. Rosenthal

23

Underlying Physiological Mechanisms
of Bariatric Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 285
Diana Vetter and Marco Bueter

24

Infant Nutrition and Obesity . . . . . . . . . . . . . . . . . . . . . . . . . . . . 297
Lisa G. Smithers and Megan Rebuli

25

Disordered Eating and Obesity . . . . . . . . . . . . . . . . . . . . . . . . . . 309
Ana Pinto-Bastos, Sofia M. Ramalho, Eva Conceição,
and James Mitchell

26

Physical Activity in Obesity and Diabetes . . . . . . . . . . . . . . . . . 321
Samannaaz S. Khoja, Sara R. Piva, and Frederico G.S. Toledo

27

Obesity Prevention in Young Children . . . . . . . . . . . . . . . . . . . . 335
Ruby Natale, Catherina Chang, and Sarah Messiah

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 351


Contributors

Mahinda Y. Abeywardena, BSc (Hons), PhD CSIRO Food and Nutrition
Flagship, Adelaide, BC, Australia
Shamim I. Ahmad, MSc, PhD School of Science and Technology,
Nottingham Trent University, Nottingham, UK
David Albuquerque, BSc, MSc, PhD Department of Life Science,
Research Center for Anthropology and Health (CIAS), University of
Coimbra, Coimbra, Portugal
Waleed Al-Khyatt, MRCS, PhD The East Midlands Bariatric and
Metabolic Institute, Royal Derby Hospital, Derby, UK
Cristina Antich Biosanitary Institute of Granada (ibs.GRANADA),
University Hospitals of Granada-University of Granada, Granada, Spain
Jean-Noël Argenson Department of Orthopaedic Surgery, Institute for
Locomotion, Aix-Marseille University, Marseille, France
Fernando De Assis Batista, MSc Laboratory of Cancer Molecular
Genetics (GEMOCA), Faculty of Medical Sciences, University of Campinas
(FCM-Unicamp), Campinas – Sao Paulo, SP, Brazil
Altaf Jawed Baig Liaquat National Hospital & Medical College, Karachi,
Pakistan
Elena Barbagelata Department of Medicine, Hospital of Sestri Levante,
Sestri Levante, Italy
Thomas M. Barber, MA Hons, MRCP, FRCP, DPhil Division of

Translational and Systems Medicine, Warwick Medical School,
The University of Warwick, Clinical Sciences Research Laboratories,
University Hospitals Coventry and Warwickshire, Coventry, UK
Warwickshire Institute for the Study of Diabetes, Endocrinology and
Metabolism, University Hospitals Coventry and Warwickshire,
Coventry, UK
Cornelius Barlascini Department of Health Medicine, Hospital of Sestri
Levante, Sestri Levante, Italy
Damien P. Belobrajdic, BSc Hons, Grad Dip Ed, PhD CSIRO Food and
Nutrition Flagship, Adelaide, BC, Australia
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xviii

Stefan Borgwardt, MD University Psychiatric Clinics (UPK), Basel,
Switzerland
Adult Psychiatric Hospital, Universitäre Psychiatrische Kliniken, Basel,
Switzerland
Marco Bueter, MD, PhD Department of Abdominal- and Transplant
Surgery, University Hospital of Zurich, Zurich, Switzerland
Maria Valeria Catani Department of Experimental Medicine and Surgery,
University of Rome Tor Vergata, Rome, Italy
Catherina Chang Florida International University, Miami, FL, USA
Eva Conceição, PhD School of Psychology, University of Minho, Braga,
Portugal
Lucas Leite Cunha, PhD Federal University of São Paulo, Sao Paulo, SP,
Brazil
Laboratory of Cancer Molecular Genetics (GEMOCA), Faculty of Medical
Sciences, University of Campinas (FCM-Unicamp, Campinas – Sao Paulo,

SP, Brazil
Louis Dagneaux Department of Orthopaedic Surgery, Institute for
Locomotion, Aix-Marseille University, Marseille, France
George K. Dimitriadis, MD, MSc (Hons) Division of Translational and
Systems Medicine, Warwick Medical School, The University of Warwick,
Clinical Sciences Research Laboratories, University Hospitals Coventry and
Warwickshire, Coventry, UK
Warwickshire Institute for the Study of Diabetes, Endocrinology and
Metabolism, University Hospitals Coventry and Warwickshire,
Coventry, UK
Silvia M. Ferolla Departmento de Clinica Medica, Faculdade de Medicina,
Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
Stephen Franks, MD, Hon MD, FRCP, FMedSci Institute of
Reproductive and Developmental Biology, Imperial College, London, UK
Natassja Gangeri, BS, DO Department of Internal Medicine, Mount Sinai
Medical Center, Osteopathic Internal Medicine Residency Program, Miami
Beach, FL, USA
Valeria Gasperi Department of Experimental Medicine and Surgery,
University of Rome Tor Vergata, Rome, Italy
Carmen Griñán-Lisón Biopathology and Regenerative Medicine Institute
(IBIMER), Centre for Biomedical Research, University of Granada,
Granada, Spain
Biosanitary Institute of Granada (ibs.GRANADA), University Hospitals of
Granada-University of Granada, Granada, Spain

Contributors


Contributors

xix

Syed Yousuf Iftikhar, DM, FRCS The East Midlands Bariatric and
Metabolic Institute, Royal Derby Hospital, Derby, UK
Syed Khalid Imam, FCPS, FACE Al Mouwasat Hospital, Jubail,
Kingdom of Saudi Arabia
Gema Jiménez Biopathology and Regenerative Medicine Institute
(IBIMER), Centre for Biomedical Research, University of Granada,
Granada, Spain
Department of Human Anatomy and Embryology, Faculty of Medicine,
University of Granada, Granada, Spain
Biosanitary Institute of Granada (ibs.GRANADA), University Hospitals of
Granada-University of Granada, Granada, Spain
Samannaaz S. Khoja, PT, MS Department of Physical Therapy, School of
Health and Rehabilitation Science, University of Pittsburgh, Pittsburgh, PA,
USA
Undine E. Lang, MD, PhD Adult Psychiatric Hospital, Universitäre
Psychiatrische Kliniken, Basel, Switzerland
Psychiatric Department, University Hospital Basel (UPK), Basel,
Switzerland
Elena López-Ruiz Biopathology and Regenerative Medicine Institute
(IBIMER), Centre for Biomedical Research, University of Granada,
Granada, Spain
Department of Health Sciences, University of Jaén, Jaén, Spain
Licínio Manco, BSc, PhD Department of Life Science, Research Center
for Anthropology and Health (CIAS), University of Coimbra, Coimbra,
Portugal
Marjory Alana Marcello, PhD Laboratory of Cancer Molecular Genetics
(GEMOCA), Faculty of Medical Sciences, University of Campinas (FCMUnicamp, Campinas – Sao Paulo, SP, Brazil
Juan Antonio Marchal Biopathology and Regenerative Medicine Institute

(IBIMER), Centre for Biomedical Research, University of Granada,
Granada, Spain
Department of Human Anatomy and Embryology, Faculty of Medicine,
University of Granada, Granada, Spain
Biosanitary Institute of Granada (ibs.GRANADA), University Hospitals
of Granada-University of Granada, Granada, Spain
Emanuele Lo Menzo, MD, PhD, FACS, FASMBS The Bariatric and
Metabolic Institute, Cleveland Clinic Florida, Weston, FL, USA
Sarah Messiah Miller School of Medicine, University of Miami, Miami,
FL, USA


xx

James Mitchell Neuropsychiatric Research Institute, Fargo, ND, USA
Department of Psychiatry and Behavioral Science, University of North
Dakota, School of Medicine and Health Sciences, Fargo, ND, USA
Ruby Natale, PhD, PsyD Division of Community Research and Training,
Miller School of Medicine, University of Miami, Miami, FL, USA
Antonello Nicolini, MD Department of Respiratory Diseases Unit,
Hospital of Sestri Levante, Sestri Levante, Italy
Clévio Nobrega, BSc, PhD Center for Neurosciences & Cell Biology
(CNC), University of Coimbra, Coimbra, Portugal
Matthieu Ollivier Department of Orthopaedic Surgery, Institute for
Locomotion, Aix-Marseille University, Marseille, France
Alex Ordonez, MD The Bariatric and Metabolic Institute, Cleveland Clinic
Florida, Weston, FL, USA
Sébastien Parratte Department of Orthopaedic Surgery, Institute for
Locomotion, Aix-Marseille University, Marseille, France
Dinesh S. Pashankar, MD, MRCP Division of Pediatric Gastroenterology,

Department of Pediatrics, Yale University School of Medicine, New Haven,
CT, USA
Madhura Y. Phadke, MD Division of Pediatric Gastroenterology,
Department of Pediatrics, Yale University School of Medicine, New Haven,
CT, USA
Uma Padhye Phatak, MD Division of Pediatric Gastroenterology,
Department of Pediatrics, Yale University School of Medicine, New Haven,
CT, USA
Ana Pinto-Bastos, MSc, PhD School of Psychology, University of Minho,
Braga, Portugal
Ines M.G. Piroddi Department of Respiratory Diseases Unit,
Hospital of Sestri Levante, Sestri Levante, Italy
Sara R. Piva, PhD, PT, OCS, FAAOMPT Department of Physical
Therapy, School of Health and Rehabilitation Science,
University of Pittsburgh, Pittsburgh, PA, USA
Paul Poirier, MD, PhD, FRCPC, FACC, FAHA Cardiac Prevention/
Rehabilitation Program, Department of Cardiology, Institut universitaire
de cardiologie et de pneumologie de Québec, Québec, QC, Canada
Faculty of Pharmacy, Université Laval, Québec, QC, Canada
Sofia M. Ramalho, MSc School of Psychology, University of Minho,
Braga, Portugal
Megan Rebuli Discipline of Public Health, School of Population Health,
The University of Adelaide, Adelaide, Australia

Contributors


Contributors

xxi

Jun Ren Center for Cardiovascular Research and Alternative Medicine,
University of Wyoming College of Health Sciences, Laramie, WY, USA
Raul J. Rosenthal, MD, FACS, FASMBS The Bariatric and Metabolic
Institute, Cleveland Clinic Florida, Weston, FL, USA
Isabella Savini Department of Experimental Medicine and Surgery,
University of Rome Tor Vergata, Rome, Italy
Nina Schweinfurth University Psychiatric Clinics (UPK), Basel,
Switzerland
Cátia B. Silva, MSc School of Psychology, University of Minho, Braga,
Portugal
Lisa G. Smithers Discipline of Public Health, School of Population
Health, The University of Adelaide, Adelaide, Australia
Samuel Snyder, DO Department of Internal Medicine, Nova Southeastern
University College of Ostepathic Medicine, Fort Lauderdale, FL, USA
Samuel Szomstein, MD, FACS, FASMBS The Bariatric and Metabolic
Institute, Cleveland Clinic Florida, Weston, FL, USA
Helena Tizon-Marcos, MD, MSc Department of Cardiology,
Interventional Cardiology and Cardiac Magnetic Resonance Imaging,
Hospital del Mar, Barcelona, Spain
Heart Diseases Biomedical Research Group, IMIM (Hospital del Mar
Medical Research Institute), Barcelona, Spain
Frederico G.S. Toledo, MD Division of Endocrinology and Metabolism,
Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
Stephania Triunfo, MD, PhD BCNatal-Barcelona Center for MaternalFetal and Neonatal Medicine, Hospital Clínic and Hospital Sant Joan de
Deu, University of Barcelona, Barcelona, Spain
Diana Vetter Department of Abdominal- and Transplant Surgery,
University Hospital of Zurich, Zurich, Switzerland
Marc Walter, MD, PhD University Psychiatric Clinics (UPK), Basel,
Switzerland

Adult Psychiatric Hospital, Universitäre Psychiatrische Kliniken, Basel,
Switzerland
Laura Sterian Ward, PhD Laboratory of Cancer Molecular Genetics
(GEMOCA), Faculty of Medical Sciences, University of Campinas (FCMUnicamp), Campinas – Sao Paulo, SP, Brazil
William K.K. Wu, PhD, FRCPath Department of Anaesthesia and
Intensive Care and State Key Laboratory of Digestive Diseases, The
Chinese University of Hong Kong, Hong Kong, China
Department of Medicine and Therapeutics, Institute of Digestive Disease,
The Chinese University of Hong Kong, Hong Kong, China


xxii

Jun Yu, MBBS, MMed, MD, PhD Department of Medicine and
Therapeutics, Institute of Digestive Disease, The Chinese University of
Hong Kong, Hong Kong, China
Yuanyuan Zhang National Institutes of Health, Bethesda, MD, USA
Xiang Zhang, MBBS, Master of Medicine, PhD Department of Medicine
and Therapeutics, Institute of Digestive Disease, The Chinese University of
Hong Kong, Hong Kong, China

Contributors


1

White Adipose Tissue:
Beyond Fat Storage
Syed Khalid Imam

Introduction
Adipose is a loose connective tissue that fills up
space between organs and tissues and provides
structural and metabolic support. In humans, adipose tissue is located beneath the skin (subcutaneous fat), around internal organs (visceral fat), in
bone marrow (yellow bone marrow) and in the
breast tissue. Apart from adipocytes, which comprise the highest percentage of cells within adipose
tissue, other cell types are also present, such as
preadipocytes, fibroblasts, adipose tissue macrophages, and endothelial cells. Adipose tissue contains many small blood vessels as well. In the skin
it accumulates in the deepest level, the subcutaneous layer, providing insulation from heat and cold.
White adipocytes store lipids for release as
free fatty acids during fasting periods; brown adipocytes burn glucose and lipids to maintain thermal homeostasis. A third type of adipocyte, the
pink adipocyte, has recently been characterized
in mouse subcutaneous fat depots during pregnancy and lactation [1].
Pink adipocytes are mammary gland alveolar
epithelial cells whose role is to produce and
secrete milk. Emerging evidence suggests that
they are derived from the transdifferentiation of

S.K. Imam
Department of Internal Medicine,
Al Mouwasat Hospital, Jubail,
Kingdom of Saudi Arabia
e-mail:

subcutaneous white adipocytes. All mammals
possess both white and brown adipose tissues.
White adipocytes contain a single large lipid
droplet occupying about 90 % of the cell volume.
The nucleus is squeezed to the cell periphery and
the cytoplasm forms a very thin rim. The organelles are poorly developed; in particular mitochondria are small, elongated and have short,

randomly organized cristae. Because of these
ultrastructural characteristics, these cells are also
called unilocular adipocytes [2].
Brown adipose fat cells are smaller in size and
quantity and derive their color from the high concentration of mitochondria for energy production
and vascularization of the tissue. These mitochondria contain a unique uncoupling protein 1
(UCP1), that supports the thermogenic function
of brown adipocytes These cells are also called
multilocular adipocytes [3].
The lipid in brown fat is burned to provide high
levels of energy as heat in animals who hibernate
and infants who may need additional thermal protection. The concept of white adipose tissue as an
endocrine organ originated in 1995 with the discovery of leptin and its wide-ranging biological
functions [4]. Adipose tissue was traditionally
considered an energy storage organ, but over the
last decade, it has emerged as an endocrine organ.
It is now recognized that adipose tissue produces
multiple bioactive peptides, termed ‘adipokines’,
which not only influence adipocyte function in an
autocrine and paracrine fashion but also affect
more than one metabolic pathway [5–7].

© Springer International Publishing Switzerland 2016
S.I. Ahmad, S.K. Imam (eds.), Obesity: A Practical Guide, DOI 10.1007/978-3-319-19821-7_1

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2

To maintain normal body functions, each adipocyte secretes diverse cytokines and bioactive
substances into the surrounding environment
which act locally and distally through autocrine,
paracrine and endocrine effects. Although each
adipocyte produces a small quantity of adipocytokines, as adipose tissue is the largest organ in the
human body, their total amount impacts on body
functions. Furthermore, as adipose tissue is supplied by abundant blood stream adipocytokines
released from adipocytes pour into the systemic
circulation. In obesity the increased production of
most adipokines impacts on multiple functions
such as appetite and energy balance, immunity,
insulin sensitivity, angiogenesis, blood pressure,
lipid metabolism and haemostasis, all of which
are linked with cardiovascular disease. Obesity,
associated with unfavourable changes in adipokine expression such as increased levels of Tumor
Necrosis Factor-alpha (TNF-α), Interleukin-6
(IL-6), resistin, Plasminogen Activator Inhibitor
(PAI-1) and leptin, and reduced levels of adiponectin affect glycemic homeostasis, vascular
endothelial function and the coagulation system,
thus accelerating atherosclerosis. Adipokines and
a ‘low-grade inflammatory state’ may be the link
between the metabolic syndrome with its cluster
of obesity and insulin resistance and cardiovascular disease.

Adipokines and Their Metabolic
Function
See Table 1.1.

Leptin
Leptin, a 16-kDa adipocyte-derived cytokine is

synthesized and released from fat cells in
response to changes in body fat. It is encoded by
a gene called ob (from obesity mice), and was
named leptin from the Greek word meaning thin.
Leptin circulates partially bound to plasma proteins and enters the CNS by diffusion through
capillary junctures in the median eminence and
by saturable receptor transport in the choroid

S.K. Imam
Table 1.1 Important adipokines
Adipokines
Leptin

Adiponectin

Adipsin

IL-6

TNF

PAI-1
Resistin
Angiotensinogen
Aromatase

11Beta HSD

Metabolic functions
Improves insulin sensitivity,

inhibits lipogenesis, increases
lipolysis, satiety signals
Improves insulin sensitivity,
increases fatty acid oxidation,
inhibits gluconeogenesis
Inhibits lipolysis, increases
fatty acid re-esterification,
triglyceride storage in adipose
cells
Impairs appetite, inflammation,
insulin resistance, increases
hepatic fatty acid synthesis
Inflammation, insulin
resistance, reduces adiponectin
synthesis
Inhibits activity of tissue type
plasminogen activator
Insulin resistance, endothelial
dysfunction?
Significantly correlated with
hypertension
Driving fat to subcutaneous and
breast tissues by converting
androstenidione to estrone
Synthesizes cortisol from
cortisone

plexus. In the hypothalamus, leptin binds to
receptors that stimulate anorexigenic peptides
such as proopiomelanocortin and cocaine- and

amphetamine-regulated transcript and inhibits
orexigenic peptides, e.g. neuropeptide Y and the
agouti gene-related protein [8].
Leptin reduces intracellular lipid levels in
skeletal muscle, liver and pancreatic beta cells,
thereby improving insulin sensitivity. There is
strong evidence showing that the dominant action
of leptin is to act as a ‘starvation signal’. Leptin
declines rapidly during fasting, and triggers a rise
in glucocorticoids, and reduction in thyroxine
(T4), sex and growth hormones [9]. Moreover,
the characteristic decrease in thermogenesis during fasting and postfast hyperphagia is mediated,
at least in part, through a decline in leptin.
Therefore, leptin deficiency could lead to hyperphagia, decreased metabolic rate and changes in
hormone levels, designed to restore energy balance [10].