Metabolic Syndrome: An Important Risk Factor for Stroke, Alzheimer Disease, and Depression

428 Pages·2013·7.64 MB·English

by  Akhlaq A. Farooqui (auth.)

Akhlaq A. Farooqui
Metabolic
Syndrome
An Important Risk Factor for Stroke,
Alzheimer Disease, and Depression
Metabolic Syndrome

Akhlaq A. Farooqui

Metabolic Syndrome
An Important Risk Factor for Stroke,
Alzheimer Disease, and Depression
Akhlaq A. Farooqui
Ohio State University
Columbus , OH , USA
ISBN 978-1-4614-7317-6 ISBN 978-1-4614-7318-3 (eBook)
DOI 10.1007/978-1-4614-7318-3
Springer New York Heidelberg Dordrecht London
Library of Congress Control Number: 2013937291
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This monograph is dedicated to Tahira, my
wife, companion, colleague, and friend.

Preface
Brain function depends on the complex architecture of neuronal networks and this
complexity arises from the morphological intricacy that neurons acquire during the
course of differentiation, a process, which is regulated by growth factors, cytokines,
transcription factors and soluble as well as membrane-bound receptors. The meta-
bolic syndrome is a highly prevalent condition that affects a considerable number of
adult Americans and has become increasingly relevant to many disciplines in clini-
cal medicine. At the molecular level, metabolic syndrome is accompanied not only
by dysregulation in the expression of adipocytokines, cytokines, and chemokines,
but also by alterations in levels of lipid mediators. These changes modulate immune
response and infl ammation that lead to alterations in the hypothalamic “bodyweight/
appetite/satiety set point” resulting in the initiation and development of the meta-
bolic syndrome. Metabolic syndrome is a risk factor for neurological disorders such
as stroke, depression, and Alzheimer disease (AD). Having the metabolic syndrome
approximately doubles the risk of having a stroke, AD, and depression compared
with age-matched healthy humans.
Recent studies have also indicated that patients with metabolic syndrome and
AD show insulin resistance. Insulin not only modulates levels of β-amyloid protein
aggregation, the primary constituent of senile plaques and neuropathological hall-
marks of AD, but also inhibits the activity of glycogen synthase kinase-3, prevent-
ing the phosphorylation of tau protein and thereby inhibiting the formation of
neurofi brillary tangles, the other neuropathological hallmark of AD. Psychosocial
factors activate the HPA axis, producing hypersecretion of corticotrophin-releasing
hormone, adrenocorticotropic hormone, and cortisol. This dysregulation of the
HPA axis promotes deposition of visceral adipose tissue which secretes adipocyto-
kines and infl ammatory cytokines. These adipokines and cytokines have been
implicated in insulin resistance, an important component of the metabolic syn-
drome. The molecular mechanism underlying the mirror relationship between met-
abolic syndrome and neurological disorders is not fully understood. However, all
cellular and biochemical alterations observed in metabolic syndrome such as
impairment of endothelial cell function, abnormality in essential fatty acid
vii
viii Preface
metabolism, and alterations in lipid mediators along with abnormal insulin/leptin
signaling, and insulin resistance may represent a pathological bridge between meta-
bolic syndrome and neurological disorders such as stroke, AD, and depression.
Information on the link among metabolic syndrome, stroke, AD, and depression
is scattered throughout the literature mainly in the form of original papers and some
reviews. Many books are available on the biochemical aspects of metabolic syn-
drome, but at present there are no books on the relationship between metabolic
syndrome and neurological disorders. As baby boomers grow older, the enormous
impact of metabolic syndrome and the above mentioned neurological disorders will
be felt by the American society. At present more than 800,000 people suffer from
stroke every year (approximately 1 person every 45 s), approximately 5.1 million
people over the age of 65 in the USA suffer from AD, and about 38 million US
adults have experienced depression at some point during their lifetime. The pro-
jected cost to Medicare for treating these neurological diseases is estimated to be
about 5 trillion dollars by 2050. This number does not include other visceral and
neurological diseases. Such an amount will not only burst National Institute of
Health budget but will seriously affect the US economy. Available drugs may not
reverse the stroke, AD, and depression. However, healthy diet, regular exercise, and
retardation of metabolic syndrome may produce benefi cial effects not only on
motor and cognitive functions but also on memory defi cits that occur to some extent
during normal aging and to a large extent in stroke, AD, and depression. This mono-
graph provides readers with a comprehensive and cutting-edge description of links
among metabolic syndrome, stroke, AD, and depression in a manner that is useful
not only to students and teachers but also to researchers, dietitians, nutritionists,
and physicians.
This monograph has ten chapters. The fi rst chapter describes the effects of life-
style on metabolic syndrome and neurological disorders. Chapter 2 describes glu-
cose and fructose-induced toxicity in the liver and brain. Chapter 3 deals with the
effects of essential fatty acid metabolism on metabolic syndrome and neurological
disorders. Chapters 4 and 5 focus on cutting edge information on the contribution of
lipid mediators in the pathogenesis of metabolic syndrome and neurological disor-
ders and molecular aspects of obesity and insulin resistance in metabolic syndrome
and neurological disorders. Chapter 6 describes the effect of dietary phytochemicals
on metabolic syndrome and neurological disorders. Chapters 7 and 8 are devoted to
molecular mechanisms associated with the metabolic link among metabolic syn-
drome, stroke, and AD. Chapter 9 describes the cutting-edge information on signal
transduction processes and the metabolic link between metabolic syndrome and
depression. Chapter 1 0 provides readers with a perspective that will be important
for future research work on the relationship between metabolic syndrome and neu-
rological disorders. My presentation and demonstrated ability to present compli-
cated information on signal transduction processes in metabolic syndrome and
neurological disorders will make this book particularly accessible to neuroscience
graduate students, teachers, and fellow researchers. It can be used as a supplemental
text for a range of neuroscience and biochemistry courses. Clinicians, neuroscien-
tists, neurologists, and pharmacologists will fi nd this book useful for understanding
Preface ix
the molecular aspects of metabolic syndrome and its impact on the brain and its
vulnerability to neurological disorders. To the best of my knowledge, this mono-
graph will be the fi rst to provide a comprehensive description of signal transduction
processes associated with the relationship between metabolic syndrome and neuro-
logical disorders.
The choices of topics presented in this monograph are personal. They are based
not only on my interest in the biochemistry of metabolic syndrome, stroke, AD, and
depression but also on areas where major progress has been made. I have tried to
ensure uniformity and mode of presentation as well as a logical progression of sub-
jects from one topic to another and have provided the extensive bibliography. For
the sake of simplicity and uniformity a large number of fi gures with chemical struc-
tures of drugs used for the treatment of metabolic syndrome and neurological disor-
ders along with line diagrams of colored signal transduction pathways are also
included. I hope that my attempt to integrate and consolidate the knowledge on
metabolic links among metabolic syndrome, stroke, AD, and depression will initiate
more studies on molecular mechanisms that link metabolic syndrome with neuro-
logical disorders. This knowledge may be useful in developing novel therapeutic
interventions for metabolic syndrome, stroke, Alzheimer’s disease, and depression.
Columbus , OH, USA Akhlaq A. Farooqui