Neuron Signaling in Metabolic Regulation

Cover
Half Title
Series Page
Title Page
Copyright Page
Table of Contents
Preface
Notes on the Editor
List of Contributors
Chapter 1: Regulation of Energy Balance by Hypothalamic cAMP-Related Signaling
1.1 Cyclic AMP and Downstream Signaling
1.2 Hypothalamic Control of Energy Balance
1.3 Orexigenic Effect of cAMP Signaling in the Hypothalamus
1.4 Protein Kinase A
1.5 EPAC-Rap1 Signaling
1.5.1 EPAC1/2
1.5.2 Rap1
1.6 Gsα
1.7 Adenylyl Cyclases
1.8 Phosphodiesterase
1.9 cAMP and Leptin Action in the Hypothalamus
1.10 Potential Upstream Mediators of Hypothalamic cAMP Signaling
1.11 Conclusion
References
Chapter 2: Brain Melanocortins Regulate Weight in Animals and Humans
2.1 Introduction
2.2 The Melanocortin System
2.3 POMC
2.4 AGRP
2.5 MC4R
2.6 Leptin
2.7 Asprosin
2.8 Conclusions
References
Chapter 3: Neurotransmitter Co-transmission in Brain Control of Feeding and Body Weight
3.1 Introduction
3.2 Co-transmission in the Arcuate Nucleus Neurons
3.2.1 AgRP Neurons
3.2.2 Co-transmission from POMC Neurons
3.3 Co-transmission from Paraventricular Hypothalamic Neurons
3.4 Co-transmission from Lateral Hypothalamic Neurons
3.5 Co-transmission from VTA DA Neurons
3.6 Co-release from Hindbrain GLP1 Neurons
3.7 Summary
Acknowledgments
References
Chapter 4: Brain Glucagon-Like Peptide 1 Receptor Influence on Feeding Behavior
4.1 Introduction
4.2 Agonists for the Brain GLP-1R
4.3 Brain GLP-1R Effects on Food Intake
4.3.1 Does Endogenous Stimulation of Brain GLP-1Rs Play a Role in Feeding Control?
4.3.2 How Do Brain GLP-1Rs Affect Feeding?
4.3.3 Satiation and Satiety
4.3.4 Food Reward and Motivation
4.3.5 Feeding Effects Mediated by Hypothalamic Structures
4.3.6 Nausea, Aversion, and Stress-Induced Hypophagia
4.3.7 Effects of Fasting
4.4 Other Behavioral Effects of Brain GLP-1R Stimulation
4.4.1 Water Intake
4.4.2 Drug and Alcohol Consumption and Reward
4.4.3 Sexual Behavior
4.4.4 Non-Feeding Stress Responses and Anxiety-Like Behavior
4.5 Conclusions
Acknowledgments
References
Chapter 5: Dorsomedial Hypothalamic Regulation of Energy Balance and Glucose Homeostasis: Lessons from Adeno-Associated Virus-Mediated Gene Manipulation
5.1 Introduction
5.2 DMH Neuron Projections Determined by AAV-Mediated Humanized Renilla Green Fluorescent Protein
5.3 Determination of DMH Neuronal Functions via AAV-Mediated Gene Silencing
5.3.1 Feeding Effect of DMH NPY
5.3.2 Thermogenic Effect of DMH NPY
5.3.3 Glycemic Effect of DMH NPY
5.4 Determination of DMH Neuronal Functions via AAV-Mediated Gene Expression
5.5 Chemogenetic Determination of DMH Neuronal Functions
5.6 Optogenetic Determination of DMH Neuronal Functions
5.7 Conclusions
Acknowledgments
References
Chapter 6: The Ventromedial Hypothalamic Nucleus in the Regulation of Energy Homeostasis
6.1 Introduction
6.2 The Ventromedial Nucleus of the Hypothalamus (VMH)
6.2.1 Anatomy
6.2.2 Development and Cytoarchitecture
6.3 The Historical View on the Roles of the VMH
6.4 The SF1 Neurons
6.4.1 SF1 as a Marker of the VMH
6.4.2 SF1 Neuronal Connections
6.4.3 The Role of SF1 in the VMH
6.4.4 Genetic Modulation Reveals the Thermogenic Roles of SF1 Neurons
6.4.5 SF1 Neurons Regulate Glucose Homeostasis
6.5 Non-SF1 Neuronal Circuits in the VMH
6.5.1 VMH and ARC Crosstalk
6.5.2 Estrogen Receptor Alpha (ERα)-Expressing Neurons
6.5.3 Cholecystokinin Receptor B (CCKRB)-Expressing Neurons
6.6 Conclusions
Acknowledgments
References
Chapter 7: Current Genetic Techniques Available for Investigating Feeding Behavior and the Control of Energy Balance
7.1 Introduction
7.2 Chemogenetics
7.2.1 Chemogenetics: GPCRs
7.2.2 Chemogenetics: LGICs
7.2.3 Use of Chemogenetics
7.3 Optogenetics
7.3.1 Microbial Rhodopsins
7.3.2 Engineered Channelrhodopsins and Other Optogenetic Tools
7.3.3 Uses of Optogenetics
7.4 Genetically Encoded Indicators
7.5 Genetic Techniques in the Study of Energy Homeostasis
7.6 Conclusion
References
Chapter 8: The Central Action of Thyroid Hormone on Energy Metabolism
8.1 Introduction
8.1.1 Thyroid Hormone and Thyroid Hormone Receptor
8.1.2 Thyroid Dysfunction
8.1.3 Central Nervous System and Metabolism
8.1.4 TH Action on Metabolism Via the Central Nervous System
8.2 Central Action of TH on Energy Expenditure and Thermogenesis
8.3 Central Action of TH on Hepatic Glucose and Lipid Metabolism
8.4 Central Action of TH on Cardiovascular Function
8.5 Central Action of TH on Food Intake
8.6 Conclusion
8.6.1 Peripheral Role or Central Role?
8.6.2 Prospects
8.6.2.1 Targeted Drug Development
8.6.2.2 Novel Techniques Applied to Explore the Central Action of TH
Acknowledgments
References
Chapter 9: Oxytocinergic Regulation of Energy Balance
9.1 Introduction
9.2 Oxytocin and the Oxytocin Receptor
9.3 Regulation of Energy Balance by Oxytocin
9.4 The Neural Pathway of Feeding-Regulating Oxytocinergic Neurons
9.4.1 The Site of Oxytocin Action
9.4.2 The ARC POMC-to-PVN Oxytocin Pathway
9.4.3 The PVN Oxytocin-to-Hindbrain/Spinal Cord Pathway
9.4.4 The PVN Oxytocin-to-ARC POMC Pathway
9.4.5 The PVN Oxytocin-to-VTA Dopamine Pathway
9.4.6 The Hindbrain-to-PVN Oxytocin Pathway
9.5 Application of Genetic Techniques to Determine the Physiological Effects of Oxytocin and Neural Circuitry Involving Oxytocin Neurons
9.5.1 Gene Knockout and Knockdown
9.5.2 Reporter Lines
9.5.3 Ablation of Oxytocin Neurons
9.5.4 Manipulation of Oxytocin Release
9.5.5 Manipulation of Specific Oxytocin Neuron Activity
9.5.5.1 The ARC AgRP-to-PVN Oxytocin Pathway
9.5.5.2 The PVN Oxytocin-to-Hindbrain/Spinal Cord Pathway
9.5.5.3 The PVN Oxytocin-to-ARC POMC Pathway
9.5.5.4 The PVN Oxytocin-to-VTA Dopamine Pathway
9.6 The Possibility of Oxytocin Treatment as Anti-Obesity Therapy
9.7 Perspectives
References
Chapter 10: Lessons Learned about Metabolism from Traditional and Novel Tools for Studying the Structure and Function of the Vagus Nerve
10.1 Introduction
10.2 Tracers
10.2.1 Retrograde Tracers
10.2.1.1 Protocol
10.2.1.2 Advantages
10.2.1.3 Limitations
10.2.2 Anterograde
10.2.2.1 Protocol
10.2.2.2 Advantages
10.2.2.3 Limitations
10.2.3 What We Have Learned from Tracing Approaches
10.3 Methods to Study the Function of the Vagus Nerve
10.3.1 Vagal Nerve Stimulation
10.3.1.1 Electrode Design
10.3.1.2 Protocol
10.3.1.3 Advantages
10.3.1.4 Limitations
10.3.1.5 What We Have Learned from VNS
10.3.2 Tools to Inhibit Vagal Signaling
10.3.2.1 Vagotomy
10.3.2.1.1 Protocol
10.3.2.1.2 Advantages
10.3.2.1.3 Limitations
10.3.2.2 Selective Vagotomy
10.3.2.2.1 Protocol
10.3.2.2.2 Advantages
10.3.2.2.3 Limitations
10.3.2.3 Capsaicin
10.3.2.3.1 Protocol
10.3.2.3.2 Advantages
10.3.2.3.3 Limitations
10.3.2.4 Subdiaphragmatic Deafferentation
10.3.2.4.1 Procedure
Ventral Access
Dorsal Access
Contralateral Subdiaphragmatic Vagotomy
10.3.2.4.2 Advantages
10.3.2.4.3 Limitations
10.3.2.5 What We Have Learned from Approaches Inhibiting the Vagus Nerve
10.4 Novel Molecular and Genetic Tools
10.4.1 Cell-Type Specificity
10.4.1.1 CCK-saporin
10.4.1.1.1 Procedure
10.4.1.1.2 Advantages
10.4.1.1.3 Limitations
10.4.1.1.4 What We Have Learned from This Approach
10.4.1.2 Cre/Lox System
10.4.1.2.1 Promoters
10.4.1.2.1.1 Advantages
10.4.1.2.1.2 Limitations
10.4.1.2.1.3 New Developments
10.4.1.2.2 Retrograde Viral Mediated Cre Expression
10.4.1.2.2.1 Protocol
10.4.1.2.2.2 Advantages
10.4.1.2.2.3 Limitations
10.4.1.2.2.4 What We Have Learned Using This Approach
10.4.2 Viral Mediated Approaches to Study Vagal Afferent Neurons
10.4.2.1 Circuit Mapping
10.4.2.1.1 Transsynaptic Circuit Tracing
10.4.2.1.2 Polysynaptic Retrograde Tracing
10.4.2.1.3 Monosynaptic Retrograde Tracing
10.4.2.1.4 Anterograde Polysynaptic Tracing
10.4.2.1.5 Monosynaptic Anterograde Tracing
10.4.2.1.6 Functional Mapping
10.4.2.2 Activation Strategies
10.4.2.2.1 Short-Term Transient Neural Activation
10.4.2.2.1.1 Optogenetics
10.4.2.2.1.2 Chemogenetics
10.4.2.2.2 Chronic Stimulation
10.4.2.3 Inhibition Strategies
10.4.2.4 Imaging
10.5 Conclusions
References
Chapter 11: Neuronal Regulation of Adipose Tissue Biology
11.1 Adipose Tissue Diversity
11.2 Neuronal Control of Adaptive Thermogenesis in Brown Adipose Tissues
11.3 Neuronal Regulation of Lipolysis in White Adipose Tissues
11.4 Neuronal Control of the Browning/Beiging Process of White Adipose Tissues
11.5 Neuronal Mediation of the Adipose Tissue Endocrine Function
11.6 Neuronal Modulation of Vasculatures in Adipose Tissues
11.7 Sympathetic Innervation and Plasticity
11.8 The Pathophysiology of Sympathetic Innervations
11.9 Concluding Remarks
References
Chapter 12: Sex Differences in Feeding Regulated by Estrogen: Crosstalk between Dopaminergic Reward Circuitry and Adiposity Signals
12.1 Introduction
12.1.1 Feeding Behavior
12.1.2 Sex Differences in Eating Behaviors
12.1.3 General Effects of Estrogen on Eating Behaviors
12.2 Role of Dopaminergic Signaling in Sex Differences in Feeding Behaviors
12.2.1 Dopamine Determines Feeding Pattern and Food Choice
12.2.2 Dopamine-Mediated Behavioral Effects of Estrogen on Feeding
12.2.3 Estrogen-Mediated Feeding Effects on Dopamine
12.3 Crosstalk Between Circulating Adiposity Signals and Reward Circuitry
12.3.1 Circulating Factors Regulate Feeding Behavior Via Dopamine
12.3.2 Overview of Adiposity Signals Leptin and Insulin
12.3.3 Behavioral Effects of Estrogen on Feeding Mediated by Leptin and Insulin
12.3.3.1 Hypothalamus-Mediated Effects of Adiposity Signals on Feeding
12.3.3.2 Dopaminergic Effects of Adiposity Signals on Feeding
12.4 Clinical Implications and Future Research
12.4.1 Sex Differences in Eating Disorders and Obesity Due to Dysfunction of the Dopamine System
12.4.2 Gaps between Animal and Human Studies
12.4.3 Improvements Needed in Future Studies
Acknowledgment
Abbreviations
References
Chapter 13: High-Throughput Evaluation of Metabolic Activities Using Reverse Phase Protein Array Technology
13.1 Introduction
13.2 Materials
13.2.1 Antibodies Used in RPPA
13.2.2 Instrumentation and Small Equipment
13.2.3 Cell Culture
13.2.4 Sample Preparation
13.2.5 Reverse Phase Protein Array (RPPA) Sample Printing
13.2.6 Total Protein Staining
13.2.7 Reverse Phase Protein Array Immunostaining
13.3 Methods
13.3.1 Antibody Validation
13.3.2 Cell Culture
13.3.3 RPPA Sample Lysate Preparation
13.3.3.1 Protein Extraction (for Tissues)
13.3.3.2 Protein extraction (for Cultured Cells)
13.3.3.3 Preparation of RPPA Lysate Samples (Carried Out on the Same Day, Immediately Following the Above Lysis Preparation Procedure):
13.3.4 Reverse Phase Protein Array Design and Layout
13.3.4.1 Preparation of RPPA Controls
13.3.4.2 Design of the Slide Layout
13.3.5 Protocol for Printing Array Slides
13.3.6 Total Protein Staining and Antibody Labeling
13.3.6.1 SYPRO Ruby Total Protein Staining
13.3.6.2 Antibody Labeling
13.3.6.3 Control Slides for Data Normalization
13.3.7 Slides Scanning and Image Analyses
13.3.7.1 Slide Scanning
13.3.7.2 Image Analysis
13.3.8 Data Normalization and Data Processing
13.3.8.1 RPPA Data Normalization
13.3.8.2 Data Processing and Final Data Output
13.3.9 Statistical Analyses
13.4 Results and Discussion: An Example
13.4.1 Background
13.4.2 Changes in WT and TPC dKO MEF Cells in Response to Short-term Starvation
13.4.3 Homeostatic Alterations of Signaling Molecules between WT and TPC dKO MEF Cells
Acknowledgments
References
Index
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