Avtanski D., Poretsky L. (eds.) Obesity, Diabetes and Inflammation: Molecular Mechanisms and Clinical Management

Springer, 2023. — 235 p.Obesity is a worldwide epidemic that affects half a billion people. It has been estimated that, if current trends continue, by 2050, 60% of men and 50% of women worldwide will be obese. Hypertrophy and hyperplasia of white adipose tissue caused by overweight and obesity lead to a chronic inflammatory state, which results in impaired insulin sensitivity and the development of diabetes. Currently, the number of people affected by diabetes globally exceeds 400 million (rising more rapidly in low- and middle-income countries). In 2019, diabetes was the ninth leading cause of mortality, with an estimated 1.5 million direct deaths.
This book provides a comprehensive overview of the relationship between inflammation, obesity, and diabetes. It focuses on the pathogenesis and biological mechanisms of obesity, the interaction between adipose tissue and the immune system, the role of genetic and environmental factors, the progression of cardiovascular complications, and the association of obesity and inflammation with type 1 and type 2 diabetes, as well as gestational diabetes. This volume also includes practical recommendations for preventing and managing these conditions using both lifestyle modifications and pharmacological interventions.
Written by experts in the field, Obesity, Diabetes and Inflammation: Molecular Mechanisms and Clinical Management addresses the role of inflammation in both obesity and diabetes, its effect on vascular and non-vascular pathologies, oxidative stress, genetics, and epigenetics. This text aims to be a valuable resource for researchers, clinicians, and students of medicine at all levels.Preface
Inflammation: Pathogenesis and Biological Markers
Introduction
Brief History and Definitions
Clinical Biomarkers
Immunology of Inflammation
Innate Immune System
Cells of the Innate Immune System
Molecular Components of the Innate Immune System
Adaptive Immune System
Components of Adaptive Immunity
Chronic Inflammation Associated with Adaptive Immunity
Anti-Inflammatory Therapy
Conclusions
References
Obesity and Inflammation
Introduction
Obesity
Adipose Tissue
White Adipose Tissue and Obesity
Brown Adipose Tissue and Obesity
Obesity and Inflammation
Overview
Cytokines Involved in Obesity-Induced Inflammation
Leptin
Adiponectin
Resistin
TNFα
IL-6
Irisin
Inducers of Adipose Tissue Inflammation in Obesity
ER Stress
Imbalance in Fatty Acids Homeostasis
Hypoxia
Mitochondrial Dysfunction
Adipose Tissue Inflammation and Immune System Cells
Macrophages
Neutrophils
Dendritic Cells
Mast Cells
B Cells
T Cells
Conclusions
References
Inflammation and Diabetes Mellitus
Introduction
Epidemiology and Risk Factors
Genetics
Inflammation, the Immune System, and Diabetes
The Role of Cytokines in the Development of Diabetes
Immune Checkpoint Inhibitor-Induced Diabetes
Treatment
Metformin
Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists
Sodium-Glucose Co-Transporter 2 Inhibitors
Immune-Based Therapies
Systemic Inflammation and Diabetes
Conclusions
References
Diabetes, Obesity, and Oxidative Stress
Introduction
Oxidative Stress
Obesity, Diabetes and Insulin Resistance
Key Molecular Mechanisms of Obesity, IR and DM Include Mitochondrial Dysfunction, ER Stress and ROS-Induced DNA Damage, which Are Closely Connected with the Major Cellular Disturbances Caused by OS
Mitochondrial Dysfunction
Endoplasmic Reticulum Stress
ROS-Induced DNA Damage
Conclusions
References
Advanced Glycation End Products and Diabetes
Advanced Glycation End Products: Sources, Metabolism, Interaction with Receptors
Exogenous AGEs
Endogenous AGEs
Metabolism of AGEs
Interaction of AGEs with Receptors
AGEs in Type 2 Diabetes Mellitus: Pathophysiological Mechanisms
AGEs Are Toxic to β-Cells and Negatively Influence Insulin Production and Secretion
AGE-Induced Insulin Resistance
AGEs and Chronic Diabetic Complications
AGEs in Diabetic Cardiovascular Diseases
AGEs in Diabetic Kidney Disease
Therapeutic Options to Reduce AGEs in Diabetes
Dietary Intervention
Neutralization and Signaling Interference
Pharmacological Agents
Nutritional and Phytotherapeutic Options
References
Genetic and Epigenetic Basis of Obesity-Induced Inflammation and Diabetes
Introduction
Genetic Cause of Obesity and Leptin-Melanocortin Pathway
Monogenic Obesity
Congenital Leptin Deficiency (LEP-Related Monogenic Obesity)
Leptin Resistance (LEPR-Related Monogenic Obesity)
POMC Deficiency (POMC-Related Obesity)
MC4R Mutations
PC1/3 and PC2 Deficiency (PCSK1-Related Obesity)
SIM1 Deficiency
BDNF and NTRK2 Mutations
Syndromic Obesity
Role of Epigenetics in Obesity
DNA Methylation
Histone Modifications
Non-coding RNAs
Conclusion and Prospects for the Future
References
Inflammation and Vascular Pathologies
Introduction
Pathogenesis of Inflammation in the Development of Atherosclerosis
Inflammation and Lipid Profile
Inflammation in the Development of Acute Myocardial Infarction
Obesity and Inflammation
Cigarette Smoking and Inflammation
Therapies for Inflammation in Cardiovascular Disease
Diet, Exercise, and Weight Loss
Statin Therapy
PCSK9 Inhibitors
Eicosapentaenoic Acid
Colchicine
IL-1β Inhibition
Low-Dose Methotrexate
Conclusion
References
Environmental and Lifestyle Factors Influencing Inflammation and Type 2 Diabetes
Introduction
Role of Diet and Nutrition in Diabetes
Mediterranean Diet
Ketogenic/Very Low Carbohydrate Diets
Vegan Diet
Gluten-Free Diet
Role of Physical Activity in Diabetes
Role of the Intestinal Microflora in Obesity-Induced Inflammation and Diabetes
Intestinal Microflora and Obesity
Intestinal Microflora and Inflammation
Intestinal Microflora and T2DM
Conclusions and Further Directions
References
Inflammation in Pregnant Women with Obesity and Gestational Diabetes Mellitus
Introduction
Epidemiology of Obesity and Gestational Diabetes
Fetal Programming
Role of the Immune System in Pregnancy
Obesity
Physiology
Definition/Diagnosis
Inflammation in Pregnant Women with Obesity
Fetal Programming
Gestational Diabetes Mellitus
Physiology
Diagnosis
Role of Inflammation in Gestational Diabetes
Fetal Programming
Recommendations
Antenatal and Natal Nutritional and Behavioral Modifications
Optimizing BMI Prior to Pregnancy
Medications
Bariatric Surgery
Supplementation
Conclusions and Implications for Future Research
References
Potential Pharmaceutical and Non-pharmaceutical Approaches to Obesity and Diabetes: Focus on Inflammation
Introduction
Molecular Mechanisms
Adipose Tissue
ATMs
Pro-inflammatory Cytokines
TNFα
IL-1β
IL-6 and CRP
Leptin
Anti-inflammatory Cytokines
Adiponectin
Non-pharmacological Approaches
Nutrition and Dietary Interventions
Diet Types
Specific Foods
Exercise and Physical Activity
Pharmacological Approaches
Metformin
GLP-1 Agonists
GLP-1/GIP Dual Agonists
SGLT-2 Inhibitors
Additional Anti-Obesity Medications and Anti-Diabetic Agents
Conclusion
References
Index