Table Of ContentAdvances in Neurobiology 19
Liliana Letra
Raquel Seiça E ditors
Obesity
and Brain
Function
Advances in Neurobiology
Volume 19
Series Editor
Arne Schousboe
More information about this series at http://www.springer.com/series/8787
Liliana Letra • Raquel Seiça
Editors
Obesity and Brain Function
Editors
Liliana Letra Raquel Seiça
Institute of Physiology, Institute Institute of Physiology, Institute
for Biomedical Imaging and Life for Biomedical Imaging and Life
Sciences—IBILI Sciences—IBILI
Faculty of Medicine, University of Coimbra Faculty of Medicine, University of Coimbra
Coimbra, Portugal Coimbra, Portugal
Neurology Department
Centro Hospitalar do Baixo Vouga
Aveiro, Portugal
ISSN 2190-5215 ISSN 2190-5223 (electronic)
Advances in Neurobiology
ISBN 978-3-319-63259-9 ISBN 978-3-319-63260-5 (eBook)
DOI 10.1007/978-3-319-63260-5
Library of Congress Control Number: 2017952609
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Preface
The concept of this book arose from an increasing interest in one of the greatest
epidemics of modern societies—obesity. Just a few years ago, adipose tissue func-
tion and dysfunction were not even included in Physiology books while currently
they became the focus of extensive and exciting investigation.
Obesity and Brain Function emerges, then, by the recognition of the influence of
adipose tissue and particularly of its derived products (adipokines) on brain struc-
ture and function as well as their role in the development and progression of neuro-
logical diseases. It is written by talented basic researchers and skilled clinical
neurologists who were gathered by their interest on this particular topic and whom
the editors thank for their dedication and diligent work.
This book is expected to provide a comprehensive, though concise and practical,
review of adipose tissue biology in health and in neurological disease, also compris-
ing hot topics such as bariatric surgery and functional neuroimaging, and ultimately
serve as a useful resource to researchers and/or physicians interested in obesity.
Enjoy.
Coimbra, Portugal Liliana Letra
Raquel Seiça
v
Contents
Part I Adipose Tissue Biology and Crosstalks
1 Function and Dysfunction of Adipose Tissue . . . . . . . . . . . . . . . . . . . . 3
Paulo Matafome and Raquel Seiça
2 The Role of Brain in Energy Balance . . . . . . . . . . . . . . . . . . . . . . . . . . 33
Paulo Matafome and Raquel Seiça
3 Neuroendocrinology of Adipose Tissue and Gut–Brain Axis . . . . . . . 49
Paulo Matafome, Hans Eickhoff, Liliana Letra, and Raquel Seiça
Part II Obesity as a Risk Factor for Neurological Disease
4 Hypothalamic Dysfunction in Obesity and Metabolic Disorders . . . . 73
Sara Carmo-Silva and Cláudia Cavadas
5 Diabesity and Brain Energy Metabolism:
The Case of Alzheimer’s Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117
Susana Cardoso, Raquel Seiça, and Paula I. Moreira
6 The Influence of Adipose Tissue on Brain Development,
Cognition, and Risk of Neurodegenerative Disorders . . . . . . . . . . . . . 151
Liliana Letra and Isabel Santana
7 Cerebrovascular Disease: Consequences
of Obesity-Induced Endothelial Dysfunction . . . . . . . . . . . . . . . . . . . . 163
Liliana Letra and Cristina Sena
8 Multiple Sclerosis: Implications of Obesity
in Neuroinflammation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191
Ana Margarida Novo and Sónia Batista
vii
viii Contents
Part III Brain Function After Bariatric Surgery
9 Central Modulation of Energy Homeostasis
and Cognitive Performance After Bariatric Surgery. . . . . . . . . . . . . . 213
Hans Eickhoff
Part IV Neuroimaging in Obesity
10 Functional Neuroimaging in Obesity Research . . . . . . . . . . . . . . . . . . 239
Liliana Letra, Daniela Pereira, and Miguel Castelo-Branco
Part I
Adipose Tissue Biology and Crosstalks
Chapter 1
Function and Dysfunction of Adipose Tissue
Paulo Matafome and Raquel Seiça
Abstract Adipose tissue is an endocrine organ which is responsible for postpran-
dial uptake of glucose and fatty acids, consequently producing a broad range of
adipokines controlling several physiological functions like appetite, insulin sensi-
tivity and secretion, immunity, coagulation, and vascular tone, among others. Many
aspects of adipose tissue pathophysiology in metabolic diseases have been described
in the last years. Recent data suggest two main factors for adipose tissue dysfunc-
tion: accumulation of nonesterified fatty acids and their secondary products and
hypoxia. Both of these factors are thought to be on the basis of low-grade inflamma-
tory activation, further increasing metabolic dysregulation in adipose tissue. In turn,
inflammation is involved in the inhibition of substrate uptake, alteration of the
secretory profile, stimulation of angiogenesis, and recruitment of further inflamma-
tory cells, which creates an inflammatory feedback in the tissue and is responsible
for long-term establishment of insulin resistance.
Keywords Nutrient storage • Adipokines • Lipid intermediates • Hypoxia •
Inflammation • Angiogenesis
1.1 Adipose Tissue Structure
Adipose tissue is a complex and heterogeneous tissue composed by cells with lipid
storage functions, called adipocytes, and a stromovascular function, composed by
endothelial and mesenchymal stem cells, preadipocytes, fibroblasts, and resident
cells from the immune system (Rajala and Scherer 2003; Juge-Aubry et al. 2005a;
P. Matafome (*)
Institute of Physiology, Institute for Biomedical Imaging and Life Sciences—IBILI,
Faculty of Medicine, University of Coimbra, Coimbra, Portugal
Department of Complementary Sciences, Coimbra Health School (ESTeSC), Instituto
Politécnico de Coimbra, Coimbra, Portugal
e-mail: [email protected]
R. Seiça
Institute of Physiology, Institute for Biomedical Imaging and Life Sciences—IBILI,
Faculty of Medicine, University of Coimbra, Coimbra, Portugal
© Springer International Publishing AG 2017 3
L. Letra, R. Seiça (eds.), Obesity and Brain Function, Advances in
Neurobiology 19, DOI 10.1007/978-3-319-63260-5_1
4 P. Matafome and R. Seiça
Guilherme et al. 2008b; Christiaens and Lijnen 2010). During the embryonic devel-
opment, the vascular network develops before adipocytes and the extracellular
matrix which supports blood vessels is the first to be deposited, showing the crucial
role of the vascular system in adipose tissue development (Neels et al. 2004;
Christiaens and Lijnen 2010). In fact, during the embryonic development, a close
communication between the stromovascular fraction and the adipocytes results in a
mutual control between angiogenesis and adipogenesis. Recent data show that adi-
pocytes may develop from capillary networks as the progenitor cells respond to pro-
angiogenic stimuli in association with the expanding capillaries (Min et al. 2016).
In adult life, a well-developed vascular network is observable at the microscope
and each adipocyte is surrounded by at least one capillary (Neels et al. 2004;
Rutkowski et al. 2009; Christiaens and Lijnen 2010). The capillaries of the adipose
tissue are fenestrated and are rich in trans-endothelial channels, which allow a close
communication with the adipocytes (Christiaens and Lijnen 2010). Moreover, even in
the adult life, this vascular network is very dynamic and is continuously adapting to
changing nutritional fluxes. However, the mechanisms governing such remodeling are
still far from being understood. Interestingly, the dynamics of vascular remodeling
apparently influence adipocyte behavior during expansion. Adipocyte hypertrophy is
usually associated with the formation of aberrant capillaries, while adipocyte hyper-
plasia is usually associated with increased angiogenesis and development of new cap-
illaries. Hyperplasia is considered a harmless form of adipose tissue expansion, given
the formation of smaller well-irrigated adipocytes with lower inflammatory activity
than hypertrophic ones (Christiaens and Lijnen 2010). When the tissue is forced to
expand, the formation of local phenomena of hypoxia leads to the expression of
angiogenic factors which stimulate angiogenesis, including several cytokines and adi-
pokines. The balance between these factors determines vessel density and permeabil-
ity, and thus the “good” physiological or the “bad” pathophysiological expansion of
the adipose tissue. The mechanisms will be detailed in the following sections.
1.2 Metabolic Functions of the Adipose Tissue
Although its important endocrine functions, the primary function of the adipose tissue
is to store energy in the form of lipids, mainly in intracellular triglycerides droplets, also
regulating lipid catabolism in different tissues due to the actions of adipokines (Rajala
and Scherer 2003; Juge-Aubry et al. 2005a; Guilherme et al. 2008b). Lipid droplets are
coated by a group of proteins, which the main one is Perilipin A (Per A), which prevent
the contact between the stored triglycerides and the cytoplasm. In times of energetic
need, such triglycerides are quickly hydrolyzed into free fatty acids and glycerol, a
process called lipolysis, and released to the blood in order to feed other organs demands
(Arner 2005; Guilherme et al. 2008b; Galic et al. 2010). Thus, the adipose tissue is able
to recognize the metabolic state of the organism, not only by local energetic sensors, but
also through different inputs coming mainly from the gut after and between meals.
Moreover, adipocytes also regulate cholesterol metabolism, as they are able to produce
high-density lipoproteins (HDL) in order to send excessive cholesterol to the liver.
