Obesity and Cancer 9789811618451, 9789811618468

Table of contents :
Acknowledgement
Contents
About the Editors
1: Obesity-Induced Chronic Low-Level Inflammation and Cancers
1.1 Introduction
1.2 Inflammatory Mechanisms in Obesity
1.3 Obesity-Induced Cancers
1.3.1 Esophageal Adenocarcinoma
1.3.2 Gallbladder Cancer
1.3.3 Liver Cancer
1.4 Obesity-Induced Gastrointestinal Complications
1.5 Conclusion
References
2: Adipose Tissue Produced Estrogen as Risk Factors for Cancers
2.1 Introduction
2.2 Abrupt Production of Estrogen by Fat/Adipose Tissue
2.3 Role of Increased Estrogen Levels as Risk Factors for Breast Cancer
2.4 Role of Increased Estrogen Levels as Risk Factors for Endometrial Cancer
2.5 Role of Increased Estrogen Levels as Risk Factors for Ovarian Cancer
2.6 Role of Estrogen Signaling Pathway Related to Obesity and Cancer
References
3: Insulin and Insulin-Like Growth Factor-1 Associated Cancers
3.1 Introduction
3.2 Insulin and IGF Signaling Systems to Exaggerate Neoplasm
3.2.1 Receptors
3.2.2 Ligands
3.2.3 Binding Proteins
3.3 Pathophysiology of Hyperinsulinemia and Dyslipidemia in Cancers
3.3.1 Hyperglycemia
3.3.2 Dyslipidemia
3.4 Adipose Tissue Factor: Adipokines
3.5 Types of Cancers Associated with Hyperinsulinemia
3.5.1 Role of Insulin and IGF-1 in Colon Cancer
3.5.2 Role of Insulin and IGF-I in Prostate Cancer
3.5.3 Role of Insulin and IGF-1 in Kidney Cancer
3.6 Gut Microbiome in Obesity, Diabetes, and Cancer
3.7 Conclusion
References
4: Adipokines Play Important Role in Cell Proliferation and Anti-proliferation
4.1 Introduction
4.2 Adipokines Regulate Adipose Tissue Homeostasis
4.3 Overview of Adipokine Functions in Obesity
4.3.1 Leptin
4.3.1.1 Leptin and Leptin Receptor Signalling in Obesity
4.3.1.2 Leptin Cause Proliferation and Activation of Immune Cells and Inflammation in Obesity
4.3.1.3 Leptin Induces Cellular Proliferation, Inhibit Apoptosis in Obesity-Related Breast Cancer
4.3.2 Adiponectin
4.3.2.1 Adiponectin Signalling and Its Role in the Regulation of Lipid Metabolism, Insulin Sensitivity, Glucose Metabolism, an...
4.3.2.2 Adiponectin Protects Against Obesity-Induced Inflammation
4.3.2.3 Adiponectin Plays an Important Role in Cell Growth Inhibition in Breast Cancer
4.3.3 Angiotensinogen
4.3.4 Omentin-1
4.3.5 Osteopontin
4.3.6 Resistin
4.3.7 Visfatin
4.3.8 Ghrelin
4.3.9 Obestatin
4.3.10 Wingless-Type MMTV Integration Site Family 5A (WNT-5A)
4.3.11 Lipocalin 2 (LCN-2)
4.3.12 Chitinase-3-Like Protein 1 (CHI3L1)
4.3.13 Chemerin
4.3.14 Tenascin C (TNC)
4.3.15 Calprotectin
4.3.16 Fibroblast Growth Factor 21 (FGF21)
4.3.17 Interleukin-32 (IL-32)
4.4 Conclusions and Future Prospective
References
5: mTOR and AMP-Activated Protein Kinase in Obesity and Cancer
5.1 Introduction
5.2 Adipose Tissue Inflammation and Development of Tumor Microenvironment
5.3 Obesity Induced mTOR Activity Leads to Uncontrolled Cell Proliferation, Metabolic Alteration, and Tumorigenesis
5.3.1 mTOR Signaling in Adipose Tissue
5.3.2 mTOR Complex
5.3.2.1 mTORC1 Downstream Signaling
5.3.2.2 mTORC2 Downstream Signaling
5.3.3 mTOR Signaling in Adipogenesis
5.3.4 mTOR Signaling in Lipolysis
5.3.5 mTOR Signaling in Tumor Growth, Metabolism, and Cancer
5.3.6 mTOR Signaling in Tumor Development
5.3.7 Targeting mTOR Pathway in Cancer
5.3.7.1 Esophageal Adenocarcinoma
5.3.7.2 Gastric Cancer
5.3.7.3 Hepatocellular Carcinoma
5.3.7.4 Prostate Cancer
5.4 Reduced AMPK Activity Leads to Adipose Tissue Inflammation and Enrichment of Tumor Microenvironment in Obesity
5.4.1 AMPK Signaling
5.4.2 AMPK Signaling Regulates Lipid Metabolism and Obesity
5.4.3 AMPK Signaling in Cancer
5.4.3.1 Anti-Tumor Effect of AMPK
5.4.3.2 AMPK as Drug Target in Cancer
5.5 Conclusion
References
6: Immune Response and Oxidative Stress in Obesity-Induced Cancer
6.1 Introduction
6.2 Obesity Regulatory Hormones and Their Role in Cancer
6.2.1 Insulin
6.2.2 Leptin
6.2.3 Adiponectin
6.3 Obesity-Associated Inflammation and Its Role in Cancer
6.3.1 Obesity and Inflammation
6.3.2 Role of Obesity-Associated Inflammation in Cancer
6.4 Alterations in the Immune Response by Obesity
6.4.1 Innate Immune Response and Obesity
6.4.2 Adaptive Immune Response and Obesity
6.5 Oxidative Stress in Obesity
6.6 Role of Obesity-Associated Oxidative Stress in Cancer
6.7 Conclusion and Future Prospective
References
7: Role of Gene Polymorphism in Obesity and Cancer
7.1 Introduction
7.2 Epidemiology and General Factors
7.3 Polymorphism and Obesity
7.4 Obesity Induced Cancer
7.4.1 Breast Cancer
7.4.2 Prostate Cancer
7.4.3 Lung Cancer
7.4.4 Hepatocellular Carcinoma
7.5 Relation of Gene Polymorphism and Obesity
7.6 Relation of Gene Polymorphism and Cancer
7.7 Conclusion and Future Perspectives
References
8: Therapeutic Role of Green Tea in Obesity and Cancer
8.1 Introduction
8.2 Green Tea Composition
8.3 Role of Green Tea in Obesity
8.3.1 Energy Expenditure
8.3.2 Appetite Inhibition
8.3.3 Modifications in Lipid Metabolism
8.3.4 Decline in Absorption of Nutrients
8.4 Role of Green Tea in Cancer
8.4.1 Effect of Green Tea on Tumour Suppressor Gene
8.4.2 Regulation of Apoptotic Pathways by EGCG
8.4.3 Inhibition of Angiogenesis by EGCG in Cancer Cells
8.4.4 Effect of Green Tea on TNF-α
8.4.5 Effects of Green Tea on Activity of Telomerases
8.4.6 Effect of Green Tea in Metastasis Inhibition
8.5 Anticancer Mechanisms of Green Tea
8.6 Other Health Benefits of Green Tea
8.6.1 Effects on Metal Ion Absorption
8.6.2 Effects on Drug Bio-Transforming Enzymes
8.6.3 Effects on Oxidative Stress and Antioxidant Markers
8.7 Conclusion and Future Perspectives
References
9: Effect of Dietary Phytochemicals in Obesity and Cancer
9.1 Introduction
9.2 Dietary Phytochemicals
9.2.1 Classes of Dietary Phytochemicals
9.3 Diabetes
9.4 Dietary Phytochemicals and Diabetes
9.5 Cancer
9.6 Dietary Phytochemicals and Cancers
9.6.1 Curcumin
9.6.2 Resveratrol
9.6.3 Genistein
9.6.4 Epigallocatechin Gallate (EGCG)
9.7 Effect of Phytochemicals in Obesity Induced Cancer
9.7.1 Obesity Induced Cancers
9.7.1.1 Obesity Induced Cancer Mechanism
9.7.2 Effects of Phytochemicals on Obesity Associated Cancer
9.7.2.1 Resveratrol
9.7.2.2 Curcumin
9.7.2.3 Ursolic Acid
9.7.2.4 Quercetin
References
10: Resveratrol as Anti-Obesity and Anticancer Agent
10.1 Introduction
10.2 Structure, Metabolism, and Bioavailability of Resveratrol
10.3 Effect of Resveratrol on Adipogenesis
10.4 Effect of Resveratrol on Lipogenesis and Lipolysis
10.5 Impact of Resveratrol-Modulated Gut Microbiota on Obesity
10.6 Anticancer Potential of Resveratrol and Associated Mechanisms
10.7 Adjunct Therapeutic Potential of Resveratrol Against Cancer
10.8 Conclusion
10.9 Future Prospective
References
11: EGCG as Anti-Obesity and Anticancer Agent
11.1 Introduction
11.2 Structural Details of EGCG
11.3 EGCG and Obesity
11.3.1 Role of EGCG Modulated Fat Metabolism in Obesity Prevention
11.3.2 Antioxidant Properties of EGCG in Obesity Prevention
11.3.3 Effect of EGCG on Adipogenesis and Apoptosis of Adipocytes
11.3.4 Effect of EGCG on Food Intake
11.4 EGCG and Cancer
11.4.1 Anti-Proliferative and Apoptosis Inducing Ability of EGCG Against Cancer
11.4.2 Anti-Angiogenic, Anti-Invasive, and Anti-Metastatic Potential of EGCG
11.4.3 Adjunct Therapeutic Potential of EGCG Against Cancer
11.5 Conclusion and Future Prospective
References
12: miRNAs as Therapeutic Target in Obesity and Cancer
12.1 Biology of MicroRNAs (miRNAs)
12.2 Obesity and miRNAs
12.3 miRNAs and Cancer
12.4 miRNA Association with Obesity and Cancer and Signaling Mechanism
12.5 miRNA Association with Obesity and Breast Cancer
12.6 miRNA Association with Obesity and Hepatocellular Carcinoma
12.7 miRNA Association with Obesity and Prostate Cancer
12.8 miRNA Association with Obesity and Clear Cell Renal Cell Carcinoma (ccRCC)
12.9 miRNA Association with Obesity and Colorectal Carcinoma
12.10 miRNA Association with Obesity and Polycystic Ovary Syndrome (PCOS)
12.11 MicroRNA Delivery and Therapeutic Approach
12.12 Conclusion
References
13: In Silico Updates on Lead Identification for Obesity and Cancer
13.1 Introduction
13.2 In Silico Targets in Obesity and Cancer
13.2.1 Insulin and IGF Pathway
13.2.2 Adipokine Signaling
13.2.3 Fatty Acid Metabolism
13.2.4 Tumor Necrosis Factor α (TNF-α)
13.3 In Silico Methods for Lead Identification
13.3.1 High Throughput Virtual Screening (HTVS)
13.3.2 Molecular Docking
13.3.2.1 Types of Molecular Docking
13.3.2.2 Analysis of Molecular Docking Results
13.3.2.3 Tools for Molecular Docking
13.3.3 Pharmacophore Modeling
13.3.3.1 Tools for Pharmacophore Modeling
13.3.3.2 Generation of Pharmacophore Model
13.3.3.3 Validation of Pharmacophore Model
13.3.4 Quantitative Structure-Activity Relationship (QSAR) Analysis
13.3.4.1 Tools for QSAR Analysis
13.3.4.2 Process of QSAR Analysis
13.3.5 Molecular Dynamics (MD) Simulation
13.3.5.1 Tools of MD Simulation
13.3.5.2 Setting Up MD Simulation
13.3.5.3 Analysis of MD Simulation Results
Trajectory Analysis
Principal Component Analysis
Cluster Analysis
Free Energy Landscape
13.3.6 Protein Modeling
13.3.6.1 Tools for Protein Modeling
13.3.6.2 Types of Protein Modeling
13.3.6.3 Analysis of Modeling Results
13.3.7 ADMET Prediction
13.3.7.1 Tools for ADMET Prediction
13.3.8 Sequence Analysis
13.3.8.1 Types of Sequence Analysis
13.4 Conclusion
References
14: In Vivo Models for Obesity and Obesity Related Carcinogenesis
14.1 Introduction
14.1.1 Key Factors Influencing Obesity and Obesity Related Cancer Research Using In Vivo Models
14.1.2 Physico-Chemical Methods and Tools to Measure Body Fat and Obesity
14.2 In Vivo Models for Obesity Research
14.2.1 Caenorhabditis elegans, Drosophila melanogaster, and Danio rerio
14.2.2 Rodent Models
14.2.2.1 Diet-Induced Obesity (DIO)
14.2.2.2 Sex/Gender of the In Vivo Animal Models
14.2.2.3 Age of the Animals
14.2.2.4 Nutritional Quality or Diet Regimen of the Animals
14.3 In Vivo Models for Obesity Related Carcinogenesis
14.3.1 Obesity Related Gastric Cancer
14.3.2 Obesity Related Liver Cancer
14.3.3 Obesity Related Pancreatic Cancer
14.3.4 Obesity Related Colon Cancer
14.3.5 Obesity Linked Prostate Cancer
14.3.6 Obesity Related Breast Cancer
14.3.7 Obesity Related Ovarian Cancers
14.4 Novel Knockout or Altered Expression Strategies
14.4.1 Epigenetic Inheritance of Diet Induced Obesity
14.4.2 Monogenic Rodent Models
14.4.3 Polygenic Rodent Models
14.4.4 Mechanically and Chemically Induced Animal Models of Obesity
14.5 Combined In Vivo Models for Obesity and Obesity Related Cancer Research
14.5.1 Tsumura Suzuki Obese Diabetes (TSOD) Mouse Model
14.5.2 Mito-Ob and mMito-Ob Mouse Models
14.6 Limitations of Currently Available In Vivo Models for Obesity Related Carcinogenesis Research
14.7 Conclusions and Future Direction
References
15: Estrogen Signaling Based Current and Potential Therapies Against Obesity and Related Diseases
15.1 Introduction
15.2 Estrogen Receptor Mechanism of Action
15.3 The Connection Between Obesity and Breast Cancer (BrCa) Risk
15.4 Estrogen Receptors in Osteoporosis
15.5 Estrogen Signaling Based Therapy for Neurodegenerative Diseases
15.5.1 Estrogen Based Therapy for Alzheimer´s Disease (AD)
15.5.2 Estrogen Based Therapy for Parkinson´s Disease (PD)
15.5.3 Effect of Estrogen on Frontotemporal Dementia
15.5.4 Estrogen Based Therapy of Amyotrophic Lateral Sclerosis (ALS)
15.6 Role of Estrogen Signaling in the Treatment of Cardiovascular Diseases
15.6.1 Estrogen and Oxidative Stress
15.6.2 Effect of Estrogen Against Fibrosis
15.6.3 Estrogen in Protecting the Vascular Injury and Inflammation
15.6.4 Estrogen in Angiogenesis
15.7 Estrogen Receptors and Diabetes Mellitus
15.7.1 Estradiol in the Regulation of Glucose Homeostasis
15.7.2 Estrogen in Glucose Uptake and Transporters
15.7.3 Selective ERα and/or ERbeta Modulators in GLUT4 Expression
15.8 Estrogen Signaling in Controlling Obesity
15.8.1 Estrogens and Estrogen Receptors in Regulating Fat Metabolism
15.8.2 Estrogen-Mediated Regulation of Adipocyte Cellularity
15.8.3 Estrogen Regulation of Appetite and Satiety
15.8.4 Estrogen Regulation of Energy
15.9 Estrogen Receptor and Gastrointestinal Disease
15.9.1 Role of Estrogen in Gastric Cancer
15.9.2 Role of Estrogen in the Mucosal Barrier
15.9.3 Estrogen and Intestinal Inflammation
15.10 Conclusion
References
16: Autophagy at the Crossroad of Obesity-Mediated Cancer Progression
16.1 Introduction
16.2 Autophagy
16.2.1 Autophagy Pathway
16.2.2 Regulators of Autophagy
16.3 Role of Obesity in Cancer
16.3.1 Autophagy Impairment in Obesity
16.3.2 Obesity Predisposes to Cancer Progression
16.3.3 Obesity Impaired Signaling Predisposes to Cancer
16.3.3.1 IGF Signaling
16.3.3.2 Leptin Signaling
16.3.3.3 Adiponectin Signaling
16.3.3.4 IL-6 Signaling
16.3.3.5 TNF-α Signaling
16.3.4 Autophagy as a Therapeutic Target for Obesity-Associated Cancers
16.4 Autophagy Regulation in Cancer
16.4.1 Dual Role of Autophagy in Cancer
16.4.1.1 Autophagy in Tumor Suppression
16.4.1.2 Autophagy in Cancer Progression
16.4.2 Autophagy Modulating Anticancer Phytochemicals
16.5 Conclusion and Future Prospective
References