Table Of ContentVisceral and Ectopic Fat
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Visceral and Ectopic Fat
Risk Factors for Type 2 Diabetes,
Atherosclerosis, and Cardiovascular Disease
Edited by
Hildo J. Lamb
Prof. Hildo J. Lamb, MD, PhD. Department of Radiology,
Cardio Vascular Imaging Group (CVIG), Leiden University Medical Center,
Leiden, the Netherlands
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Contents
List of contributors xiii Sex 21
Preface xvii Genetics of visceral fat accumulation 21
Ethnicity 21
Chronic stress (cortisol) 21
Behavioral determinants of visceral fat 21
Part I Measurement of visceral fat in children 22
Fat stores Imaging techniques 22
The waist circumference or waist/height ratio
1. Overall, abdominal, and visceral as a measure of visceral fat in clinical
obesity in men and women: an practice and public health 22
Classification of abdominal obesity in children
introduction
3 by the waist/height ratio 22
Visceral fat and metabolic risk factors in
Rene´e de Mutsert and Jean-Pierre Despre´s
children and adolescents 23
Overweight and obesity: definition, Conclusions 23
prevalence, and relation to disease 3 References 24
Definition of overweight and obesity 3
Prevalence of overweight and obesity 5 3. Brown adipose tissue: metabolic role
Obesity-related mortalityand diseases 6 and non-invasive quantification in
Body fat distribution: abdominal obesity,
humans
25
visceral fat, and ectopic fat 8
Body fat distribution and abdominal obesity 8 Andreas Paulus and Matthias Bauwens
Visceral adipose tissue and subcutaneous
BAT physiology 25
adipose tissue 9
Background on historyof BAT: perceived
Lipid overflow hypothesis and ectopic fat
impact on human health and scientific
accumulation 11
interest in past three decades 25
Sex differences in body fat distribution and
Overviewof potential analysis techniques for
health consequences 11
assessing BATactivity 26
Summaryand conclusion 14
Invasive techniques 29
References 14
Noninvasive techniques 29
Overviewof tracers with their molecular
2. Obesity and fat distribution in targets 31
children and adolescents 19 Discussion: clinical applications? 32
References 33
Jacob C. Seidell
Childhood obesity has reached pandemic 4. Epicardial and pericoronary fat 39
proportions 19
Pa´l Maurovich-Horvat and Gyo¨rgy Jermendy
Abdominal obesity in children is a better
indicator of health risks than BMI 19 Introduction 39
Visceral fat in relation to cardiomentabolic Terminology 39
health in young people 20 Anatomical characteristics of EAT 40
Determinants of visceral fat in children and Data based on autopsy 40
adolescents 21 Findings from clinical settings 41
v
vi Contents
Biochemical features and physiological Ectopic lipids in the context of negativeenergy
function of EAT 41 balance 75
Cardiac imaging of EAT 42 Single bout of exercise 75
EAT in the pathomechanism of atherosclerosis 44 Fasting 78
EAT in other cardiac diseases 47 Ectopic lipids in the context of positiveenergy
Atrial fibrillation 47 balance 78
Heart failure 47 Short-term high fat diet 78
Inflammation 48 Long-term high fat diet 78
Epicardial fat necrosis 48 High fructose/glucose diet 78
EAT in metabolic diseases 49 References 79
EAT in patients with COVID-19 49
Treatment options for modifying EAT volume 50 7. Nonalcoholic fatty liver disease: from
References 50 a benign finding to a life-threatening
cardiometabolic liver disease
83
Part II Koen C. van Son, A.G. (Onno) Holleboom and
Maarten E. Tushuizen
Ectopic fat stores
Introduction 83
5. Non-invasive profiling of ectopic and Pathogenesis 84
adipose lipids using magnetic Genetic and epigenetic determinants 84
Nutrition 85
resonance spectroscopy and imaging
59 Insulin resistance and lipotoxicity 86
Radka Klepochova´ and Martin Kr(cid:1)s(cid:1)sa´k Inflammation and necroapoptosis 86
Adipocytokines 86
Introduction 59 Formation of fibrosis 86
Lipid composition and its consequences in
Urea cycle dysregulation 86
magnetic resonance spectroscopy 60 Bile acids 87
In vivo magnetic resonance spectroscopy 60 Microbiome 87
Magnetic resonance spectroscopydata
Clinical consequences 87
acquisition 61 Liver cirrhosis 87
Analysis of the magnetic resonance
Hepatocellular carcinoma 87
spectrscopydata 64 Cardiovascular disease 87
Magnetic resonance imaging 66 Diagnostics 88
Applications 66 Treatment 88
Adipose tissue (deep subcutaneous adipose
Obesityand lifestyle 88
tissue/visceral adipose tissue/brown adipose
Nutrition 89
tissue) 66 Insulin sensitivity 89
Bone marrow fat 67 GLP1 receptor agonists and GLP1 analogs 89
Breast 68 SGLT2 inhibitors 89
Liver 68 Lipotoxicity 89
Heart 69 Oxidative stress 89
Skeletal muscle 70 Bile acids 90
Summary 70 Apoptosis 90
References 70 Inflammation and fibrosis 90
Combination therapy 90
6. Flexibility of ectopic lipids in
Probiotics andfecal microbiometransplantation 90
skeletal/cardiac muscle and liver
75 Development and implementation of clinical
care paths and guidelines for NAFLD 91
Hannah Loher, Chris Boesch, Roland Kreis and
Primary care 91
Emanuel Christ
Secondaryand tertiary care 91
Measurement of the flexibilityof ectopic lipids 75 Conclusion 92
Biopsy 75 References 92
Contents vii
8. Myocardial lipidsdtechniques and
Imaging-based quantification 141
applications of proton magnetic Clinical implications of excessive kidney fat 142
resonance spectroscopy of the Association with chronic kidney disease and
human heart insulin resistance 142
99
Association with cardiovascular diseases 142
Adrianus J. Bakermans Implications for other diseases 143
Localized proton magnetic resonance Changes of excessive kidney fat after
spectroscopyof the heart 99 intervention 143
Summary and perspectives 143
Quantification of myocardial metabolite
References 144
content 104
Lipids in the healthy human
11. Skeletal muscle fat
myocardiumdeffects of nutrition, fasting, 149
and exercise 106 Ivica Just and Martin Kr(cid:1)s(cid:1)sa´k
Gender 106
Introduction 149
Aging 106
Skeletal muscle fat infiltration 149
Body mass index 106
Flexibilityof IMAT fatty infiltration 151
Athletes and exercise 107
Intramyocellular lipids 152
Nutrition 107
Myocardial lipids in disease 108 Flexibilityof IMCL 154
Methods to assess lipids in the muscle 155
Insulin resistance and type 2 diabetes 108
Computed tomographydCT 155
Other diseases 109
Concluding remarks and outlook 110 MRI of skeletal muscle 156
Postprocessing and assessment of fat
References 110
infiltration imaging 157
9. Pancreas ectopic fat: imaging-based MRS of skeletal muscle 158
Postprocessing and quantitation of 1H-MR
quantification
117 spectra from skeletal muscle 159
Alexandre Triay Bagur, Matthew Robson, Summary 160
Daniel Bulte and Michael Brady References 161
Introduction 117 12. Bone marrow adipose tissue
169
Pancreas and ectopic fat 118
Pancreas state assessment 120 Be´ne´dicte Gaborit, Sonia Severin and
Information from MRI 122 Philippe Valet
Pancreas volume 122 Abbreviations 169
MRI-derivedfat fraction 122 Introduction 170
Pancreas morphology 123 Bone marrow fat origin 170
Pancreas fibroinflammation 125 Main characteristics in physiology 171
Big Data and AI 125
Main characteristics 171
Future directions 126
Variation during growth 171
References 127
Variation with aging 172
Regional specific differences in BMAT
10. Fat accumulation around and
composition 172
within the kidney
131 Effect of exercise and caloric restriction 173
Impact of unloading 173
Ling Lin, Ilona A. Dekkers and Hildo J. Lamb
Microscopic aspect 174
Introduction 131 In vivo imaging 174
Perirenal fat and renal sinus fat 131 Computed tomography 174
Anatomical characteristics 131 Magnetic resonance imaging 176
Histological and pathophysiological Secretory profile and endocrine regulation
characteristics 134 of BMAT 178
Imaging-based quantification 135 BMATand skeletal health 179
Renal parenchyma triglyceride 139 BMATand hematopoiesis 180
Histological characteristics and BMAT in cancer 181
pathophysiological relevance 139 BMATand metabolic diseases 181
viii Contents
Concluding remarks 182 Adipose tissue and signaling pathways in
References 183 diabetes and heart disease 218
Sex differences in adipose tissue remodeling
effects on cardiovascular disease 221
Part III Adiponectin, proinflammatory
adipocytokines, and cardiovascular disease
Regulation of fat stores
in diabetes 222
Imaging ectopic adiposity in patients with
13. Regulation of fat storesd
endocrinological pathways type 2 diabetes mellitus 222
193 Conclusions 223
Peter Wolf, Thomas Scherer and References 223
Michael Krebs
16. Cardiovascular disease
229
Insulin 193
Thyroid hormone 195 Michiel Sala, Albert de Roos and
Growth hormone 196 Hildo J. Lamb
Cortisol 198 Introduction 229
Sex hormones 198 Obesity hypertension: role of magnetic
Summary 200 resonance imaging 229
Acknowledgments 201 Fat deposits in obesity hypertension 230
References 201 Cardiovascular structure and function in
14. Inflammation of the adipose tissue: obesity hypertension 232
Coronary arterydisease in obesity 234
metabolic consequences during
Arrhythmias 237
weight (re)gain and loss
205 Heart failure 238
Conclusion 241
Mandala Ajie and Rinke Stienstra
References 241
Introduction 205
Chronic low-grade inflammation of the 17. Obesity in relation to cardiorenal
adipose tissue 205 function
243
Weight gain 206
Weight loss 208 Isabel T.N. Nguyen, Jaap A. Joles,
Weight regain 209 Marianne C. Verhaar, Hildo J. Lamb and
Adipose tissue inflammation during obesity: Ilona A. Dekkers
howdoes it lead to complications? 211 Introduction 243
Insulin resistance 211 Obesity-related cardiorenal dysfunction 243
Atherosclerosis 211
Overview of five-part classification system
Determining adipose tissue inflammation 211
for cardiorenal syndrome 243
Conclusion 212
The pathophysiology of cardiorenal
References 212
syndrome 244
Preclinical studies 247
Obese animal models of cardiorenal
Part IV
syndrome 247
Clinical aspects The Zucker rat and substrains as proposed
models of the metabolic cardiorenal
15. Role of adipose tissue remodeling syndrome 250
in diabetic heart disease Abnormalities in cardiac function in obesity 250
217
Abnormalities in renal function in obesity 252
Amanda MacCannell, Sam Strawand CKD as a risk factor for HFpEF in obese
Eylem Levelt animals 252
Adipose tissue physiology in health and the Sex differences in the cardiorenal interaction 253
Epidemiological and translational studies in
pathophysiological role of adipose tissue
in transition from obesity to diabetes 217 humans 253
Contents ix
19. Obesity and the brain: structural
Estimating obesity’s risk for renal and cardiac
dysfunction 253 and functional imaging studies, and
Metabolic imaging studies of ectopic fat opportunities for large-scale
storage in heart and kidney 254 imaging genetics
281
Dietaryeffects on ectopic fat storage in heart
and kidney 255 Ilona A. Dekkers, Janey Jiang, Hildo J. Lamb
Effects of glycemic control on ectopic fat and Philip Jansen
storage in heart and kidney 258 Introduction 281
Future outlook 258 Structural brain imaging and obesity 281
Novel developments in preclinical studies 258
Body Mass Index 282
Multiorgan imaging in the management of
Fat distribution 283
CRS in obese individuals 258
Diffusion tensor imaging 283
Personalized approach in the management of
Visceral fat 283
obesity-related CRS 259
Hypothalamic function 284
Conclusion 259 Functional brain imaging studies and
Funding 259 obesity 285
References 259 Genetic analyses of obesityand the brain 288
18. Obesity and asthma Genome-wide association studies 288
265
Polygenic risk scores 290
Daisuke Murakami, Yuichi Saito and Mendelian randomization 290
Ryota Higuchi Future directions 290
Conclusions 291
Physical function: lung function and genetic
References 291
factors 265
Physical effects and genetic background of
obesityand asthma 265 Part V
Obesityand respiratory function 265
Interventions
Racial differences 266
Genetic factors in obesityand asthma 266
20. The impact of very-low-calorie
Epidemiology: clinical features and findings 267
diets on ectopic fat deposition
Epidemiological study of obesityand asthma 297
in children and adults 267
Jennifer J. Rayner and Ines Abdesselam
Epidemiological studies in children 267
Epidemiological studies in adults 269 Introduction 297
Disease pathogenesis: immunological Visceral adipose tissue 297
mechanisms 270 Hepatic ectopic fat 299
Pathogenesis of obesityand asthma 270 Very-low-calorie diet in the treatment of type
Abnormal lipid metabolism 270 II diabetes 300
Increased oxidative stress 270 Calorie restriction and cardiac lipid
Increased airway inflammation 271 deposition 301
Inflammation in adipose tissue 272 Skeletal muscle lipid metabolism and
Abnormalities in adipokines 272 very-low-calorie diets 302
Decreased steroid responsiveness 272 Impact of very-low-calorie diet on bone
Insulin resistance 272 marrow fat 303
Summary 273 Conclusion 303
Acknowledgments 273 References 304
References 273
