The Mechanobiology of Obesity and Related Diseases

298 Pages·2015·7.49 MB·English

by  Amit Gefen

Studies in Mechanobiology, Tissue Engineering and
Biomaterials 16
Amit Gefen
Dafna Benayahu Editors
The
Mechanobiology
of Obesity and
Related Diseases
Studies in Mechanobiology, Tissue Engineering
and Biomaterials
Volume 16
Series editor
Amit Gefen, Ramat Aviv, Israel
More information about this series at http://www.springer.com/series/8415
Amit Gefen Dafna Benayahu
(cid:129)
Editors
The Mechanobiology
of Obesity and Related
Diseases
123
Editors
Amit Gefen Dafna Benayahu
Faculty ofEngineering, Faculty ofMedicine, Department of Cell
Department ofBiomedical Engineering andDevelopmental Biology
TelAvivUniversity TelAvivUniversity
TelAviv Ramat Aviv
Israel Israel
ISSN 1868-2006 ISSN 1868-2014 (electronic)
ISBN 978-3-319-09335-2 ISBN 978-3-319-09336-9 (eBook)
DOI 10.1007/978-3-319-09336-9
LibraryofCongressControlNumber:2014951144
SpringerChamHeidelbergNewYorkDordrechtLondon
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Preface
Adipose tissues are responsible for the control of energy balance and lipid
homeostasis. Only in the last decade the complex functions of adipose are clari-
fying,anditbecomesevidentthatotherthanservingthepurposeofenergystorage
intheformoftriglyceridedepots,adiposeisresponsibleforsecretinghormonesand
cytokines, so it is connected to the endocrinal system as well. Adipose is now
known to also host mesenchymal stem cells (MSCs) with potential of tissue repair
and regeneration.
With respect to the energy storage capacities of adipose tissues, conventional
thinking is that adipogenesis initiates when energy intake exceeds nutritional
requirements which then affects different biochemical pathways. However, a dif-
ferent thinking is currently becoming recognized, that adipogenesis is also a
mechanosensitive-regulated process, and so, mechanotransduction plays a major
role in the development and progression of obesity, as well as of related diseases
including type-2 diabetes and insulin resistance, hyperlipidemia and hypercholes-
terolemia, vascular diseases, metabolic inflammations, and several cancers. This
volumedescribesthestate-of-knowledgeinthestudyoftheintriguingrelationships
between mechanical loading states in tissues and cells, and these serious, yet
common pathophysiologies that are all related to the increase in mass of adipose
tissues and/or hyperglycemia.
As revealed byourown research(reviewed inthisvolume),there appears tobe
fundamental interactions between the loading states in tissues and cells and adi-
pogenesis. The Israel Science Foundation kindly provided us a 4-year grant (ISF
grant no. 611/12) to research these relationships to depth, given that obesity and
diabetesarenowseenasepidemicsindevelopedaswellasindevelopingcountries.
Actually, obesity and diabetes are so close together in underlying factors and
complications that they are sometimes being referred to as one single disease
—“diabesity.”Inadditiontocarbohydrate-richandsugar-richnutrition,riskfactors
for obesity and diabetes relate to gender, age, pre-existing medical conditions, and
also, clearly to the genetics of the individual, but all these were heavily studied
before. Mechanotransduction as a direct, primary factor leading to, or accelerating
v
vi Preface
obesityanddiabetesisanewandemergingconcept,andthisbooksummarizesthe
pioneering efforts in this regard across the leading laboratories in the world.
Ourgrowingunderstandingisthatdiseasesandconditionsthattraditionallywere
neverthoughttorelatetobiomechanics(suchasbreastcancerorinfertility)arenow
fully appreciated as such, particularly at the cellular and subcellular levels. This is
truly fascinating in the sense that (bio)mechanics is found to be involved nearly
everywhere in the body! And, obesity appears to be no exception. Not only with
regardtothefactthatabnormalbodyweightiscausingwell-documentedsecondary
orthopedic disorders, e.g., gradually deforming the feet and impairing the gait
pattern, or contributing to osteoarthritis and accelerated joint wear-out (topics that
are also covered in this book). In a much more fundamental sense, biomechanics
andmechanobiologyareattherootsofobesityanddiabetesthemselves,andbegin
to play a role at the cellular, the subcellular, and even at the molecular scales.
These roots of the diseases can, for example, be seen to originate in the MSCs
thatare,asmentionedabovealready,hostedbyadiposetissues.MSCsareknownto
have the potential to differentiate into either adipose cells (adipocytes) or to other,
e.g.,myogenicorosteogeniccelltypes.Indeed,oneofthechaptershereisfocusing
on the role of mechanical stimulations in directing MSC adipogenesis. Even after
differentiation, adipocytes are still influenced by their mechanical loading envi-
ronmentandactivelyrespondtoit;specifically,asdemonstratedbyourownwork,
adipocytes have been shown to respond to static loading regimes by accelerating
adipogenesis.Wesummarizeourresearchinthisregardinthebook,bydescribing
the adipogenesis spiral, and particularly how a sedentary life style and hormonal
effectsatacellscalecanmanifestasabnormalriseinfattissue massatthewhole-
bodyscale.Themechanicalbehavioroffattissuesisstillinsufficientlyunderstood,
and one of the chapters is a comprehensive review of work to characterize this
behaviorandpropertiesinthelarge-deformationandviscoelastictestingdomain.It
is known however that internally in adipose tissues, the mechanical stiffnesses of
both the cells and extracellular matrix play a role in determining the profile of the
adipogenesis process. Indeed, one chapter discusses how matrix stiffness interacts
withadiposetissuemetabolismandalsowithinflammation,whichcouldbechronic
in adipose of morbidly obese individuals. Both the cell-scale mechanical loading
conditions and the inflammatory condition connect to mechanically activated sig-
naling pathways and molecular mechanisms, and these are discussed in several
chapters as well. Finally, the interactions of adipocytes with cells of the immune
system,thevascularsystemandcellswithamalignantphenotypearediscussed,to
show how diabetes, vascular diseases, and cancers all relate to obesity through
cellular signaling and molecular mechanisms. The roles and potential of state-of-
the-art experimental cellular and biomolecular measurement techniques, as well as
sophisticated mathematical and computational bioengineering modeling, are evi-
dent throughout the book in exploring all these exciting relationships.
The book hence summarizes the efforts of an international group of authors,
from universities and government research institutes in the USA, Japan, the
Netherlands, Australia, Finland, and Israel. The chapters included altogether
make an extremely unique comprehensive, rigorous, and concise description,
Preface vii
summarizing the state-of-science in the journey toward understanding the role of
mechanotransduction in obesity and related diseases. We are certain that scien-
tists working in the fields of obesity, diabetes, hypertension, hyperlipidemia,
orthopedic, and cancer research (which is actually where most of the biomedical
research efforts are currently focused) will find this book very useful, and so will
graduate students in medicine, bioengineering and biophysics, and medical
doctors with an interest in basic and medical sciences. Obesity is not only a
metabolic disease, it is also a mechanobiological disorder, and the present book
provides the compilation of evidence to describe it as such.
Tel Aviv, Israel Amit Gefen
Dafna Benayahu
Contents
Part I From Tissues to Cells
Mechanical Behavior and Properties of Adipose Tissue. . . . . . . . . . . . 3
Cees Oomens and Gerrit Peters
Mathematical Models of Adipose Tissue Dynamics . . . . . . . . . . . . . . . 11
Junghyo Jo, Zeina Shreif, Jonathan R. Gaillard, Matilde Arroyo,
Samuel W. Cushman and Vipul Periwal
Mechanical Stretching and Signaling Pathways in Adipogenesis. . . . . . 35
Yoshiyuki Tanabe, Maki Tanji Saito and Koichi Nakayama
Role of Mechanical Stimulations in Directing Mesenchymal Stem
Cell Adipogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
Hillary Stoll and Jung Yul Lim
The Vicious Cycle of Estrogen Consumption and Obesity:
The Role of Mechanotransduction . . . . . . . . . . . . . . . . . . . . . . . . . . . 89
Naama Shoham, Natan T. Shaked, Dafna Benayahu and Amit Gefen
Extracellular Matrix Remodeling and Mechanical Stresses
as Modulators of Adipose Tissue Metabolism and Inflammation . . . . . 105
Kyongbum Lee and Catherine K. Kuo
Part II The Biomechanics and Mechanobiology in Comorbidities
of Obesity
The Impact of Obesity and Weight Loss on Gait in Adults . . . . . . . . . 125
Tarja Lyytinen, Timo Bragge, Tuomas Liikavainio, Paavo Vartiainen,
Pasi A. Karjalainen and Jari P. Arokoski
ix
x Contents
Excessive Weight Bearing Compromises Foot Structure
and Function Across the Lifespan . . . . . . . . . . . . . . . . . . . . . . . . . . . 149
Julie R. Steele, Diane L. Riddiford-Harland and Karen J. Mickle
Obesity, Osteoarthritis and Aging: The Biomechanical Links. . . . . . . . 181
Yao Fu and Timothy M. Griffin
Impaired Neutrophil Mechanoregulation by Fluid Flow:
A Potential Contributing Factor for Microvascular Dysfunction
in Obesity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 203
Michael L. Akenhead, Xiaoyan Zhang and Hainsworth Y. Shin
Mechanotransduction and the Myogenic Response in Diabetes. . . . . . . 233
Sewon Lee, Srijita Dhar, Kwangseok Hong, Yan Yang
and Michael A. Hill
Role of Adipose Cells in Tumor Microenvironment. . . . . . . . . . . . . . . 271
Tao Zhang and Mikhail G. Kolonin
Author Index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 295