Cover -- Half-title -- Title -- Copyright -- Contents -- Preface -- Contributors -- 1 Introductory chapter -- 1. Definition of obesity -- 2. Complications of obesity -- 3. Causes of obesity -- 4. Treatments for obesity -- 5. Conclusions -- References -- 2 Genetics of human and rodent body weight regulation -- 1. Introduction -- 2. Rare monogenic obesity -- 2.1 Leptin and leptin receptor deficiencies -- 2.2 Proopiomelanocortin-derived peptides deficiency -- 2.3 Proconvertase deficiency -- 2.4 Other rare monogenetic forms -- 3. Obesity with monogenic influence -- 3.1 Mutations in the melanocortin 4 receptor -- 3.2 Other suspected genes -- 4. Polygenic obesity -- 4.1 General and theoretical approach -- 4.2 Genomic regions -- 4.3 Candidate genes -- 4.4 Genes involved in the leptin/melanocortin axis -- 4.5 Genes identified by positional cloning -- 4.6 Gene-environment interaction -- 5. Lessons learned from genetic studies -- 6. Conclusion -- Acknowledgements -- References -- 3 Hypothalamic control of energy homeostasis -- 1. Introduction -- 2. Classical role of the hypothalamus in feeding regulation -- 3. The hypothalamus mediates metabolic adaptations -- 4. Overview of hypothalamic circuits controlling energy balance -- 5. Peripheral nutrient-related signals and vagal inputs influence hypothalamic output -- 6. Integration of peripheral signals by the arcuate nucleus -- 7. Hypothalamic signal transduction -- 8. Electrophysiological responses of hypothalamic neurons to energy fluxes -- 9. Role for hypothalamic plasticity in energy balance? -- 10. Neuropeptide and neurotransmitter mediators of energy balance -- 10.1 Arcuate nucleus -- Neuropeptide Y -- Melanocortins -- Cocaine and amphetamine-regulated transcript -- Endocannabinoids -- 10.2 Paraventricular nucleus -- Thyrotropin-releasing hormone -- Corticotropin-releasing hormone.

10.3 Dorsomedial nucleus -- 10.4 Lateral hypothalamic and perifornical areas -- 10.5 Ventromedial nucleus -- 11. Brainstem pathways -- 12. Cognitive and reward pathways -- 13. Summary -- References -- 4 Leptin and insulin as adiposity signals -- 1. Summary -- 2. Introduction -- 3. Is obesity a disease? -- 4. Evidence in favor of tight regulation of energy balance -- 5. Adiposity signals -- 6. Adiposity signal definition -- 7. Current model of energy homeostasis -- 8. Insulin as an adiposity signal: the catabolic nature of insulin action in the CNS -- 9. Adiposity signal access to the CNS -- 10. Evolutionary basis of adiposity signaling -- 11. Insulin as an adiposity signal: other evidence -- 12. Leptin as an adiposity signal: other evidence -- 13. Insulin and leptin signal transduction -- 14. Cross-talk between leptin and insulin action in hypothalamus -- 15. Important unanswered questions: relative role of JAK-STAT vs. PI3K signaling -- 16. Differential coupling in anabolic (NPY) vs. catabolic (POMC) neurons -- 17. Termination of adiposity signaling -- 18. Insulin and leptin as adiposity signals, energy homeostasis and obesity -- 19. What is the difference between ''experimental obesity'' and common human obesity or rodent diet-induced obesity? -- 20. Typical obesity and CNS adiposity signal resistance -- 21. Concordance of diabetes and obesity: a common mechanism for the development of adiposity signal resistance? -- 22. Dietary induction of adiposity signal resistance and propensity to weight gain -- 23. Macronutrient composition and weight loss -- 24. ''Reward'' and potentiation of obesity -- role of insulin and leptin -- 25. Conclusions -- References -- 5 Convergence of leptin and insulin signaling networks in obesity -- 1. Introduction -- 2. Signaling networks -- 2.1 Distinct insulin and leptin signaling components -- Receptors.

JAK-STAT signaling -- 2.2 Signalling molecules common to insulin and leptin action -- The receptor substrates -- Inositol lipid signaling -- The p42/p44 MAPK cascade -- SH2-B -- Suppressor of cytokine signaling (SOCS)-3 -- The mTOR pathway -- AMP kinase -- PDE3B -- Other signaling molecules -- Common gene targets -- 2.3 Negative regulation of the pathways -- SHP2 -- PTP1B -- PTEN -- SHIP2 -- 3. Signaling mechanisms as therapeutic targets -- 3.1 Interplay between insulin and leptin signaling -- 3.2 Novel therapeutic strategies for the treatment of obesity and T2DM -- Conclusions -- References -- 6 Diet-induced obesity in animal models and what they tell us about human obesity -- 1. Introduction -- 1.1 Survival, the "thrifty phenotype" and obesity -- 1.2 Neural plasticity and the defended body weight -- 1.3 Metabolic sensing neurons and the regulation of energy homeostasis -- 2. Animal models of diet-induced obesity -- 2.1 Diet-induced obesity in rodents -- 2.2 Factors predisposing to DIO:why some individuals become obese -- 2.3 Conclusion -- 3. Diet-induced obesity in non-rodent species -- 3.1 Dogs -- 3.2 Baboons -- 3.3 Rhesus macaques -- 4. Summary and conclusions -- References -- 7 Melanocortins and the control of body weight -- 1. Introduction -- 2. Anatomy and neurochemistry of the melanocortin system -- 2.1 POMC and AGRP neurons -- 2.2 Melanocortin receptors -- 3. Comparative vertebrate physiology of the melanocortin system -- 4. Rodent genetic models of altered melanocortin function -- 5. Central actions of melanocortins in the regulation of energy balance -- 5.1 Regulation of appetite and food intake -- 5.2 Dissection of the component processes underlying melanocortin effects on intake -- 5.3 Regulation of the autonomic nervous system -- Control of brown adipose tissue and thermogenesis -- Control of white adipose tissue metabolism.

Control of insulin secretion and glucose homeostasis -- 6. Electrophysiologic actions of melanocortins -- 7. Peripheral actions of melanocortins relevant for energy balance -- 8. Pharmacotherapy -- 9. Conclusion -- Acknowledgements -- References -- 8 Role of opiate peptides in regulating energy balance -- 1. Discovery and characterization of the endogenous opioids and their receptors -- 2. Opioids and feeding behaviour: early studies -- 3. Opioids and reward-related feeding -- 4. Effects of opioids on macronutrient intake -- 5. Effect of opioid receptor subtypes and injection sites in food intake -- 5.1 Receptor subtype agonists and ventricular studies -- 5.2 Site-specific effects of opioid agonists upon feeding -- 5.3 Site-specific effects of opioid antagonists upon feeding -- 6. Opioids and feeding: molecular models -- 6.1 Ingestive behaviors affect opioid peptide and receptor genes -- 6.2 Knockout and antisense approaches alter opioid-mediated ingestion -- 7. Opioid-feeding interactions with dopamine and neuropeptides -- 8. Conclusions -- References -- 9 Ghrelin: an orexigenic signal from the stomach -- 1. Introduction -- 2. Ghrelin: the endogenous GHS -- 2.1 Ghrelin and food intake -- 2.2 Ghrelin receptorsrole in energy balance -- 2.3 Ghrelin and the hypothalamic regulation of energy balance -- 2.4 Ghrelin and appetite: is it all hypothalamic? -- The brainstem and food intake -- Ghrelin and reward circuits -- Ghrelin and circadian rhythmicity -- 2.5 Brain ghrelin? -- 2.6 Clinical implications -- 2.7 Conclusion -- References -- 10 Central nervous system controls of adipose tissue apoptosis -- 1. Background -- 2. Molecular mechanisms of apoptosis -- 3. Adipocyte apoptosis -- 4. Central nervous system control of adipose tissue apoptosis -- 4.1 Leptin -- 4.2 Melanocortins -- 4.3 Cocaine and amphetamine-regulated transcript (CART).

4.4 Ciliary neurotrophic factor -- 4.5 Sympathetic nervous system -- 5. Role of CNS in bone marrow adipose apoptosis -- 6. Conclusion -- References -- 11 Potential therapies to limit obesity -- 1. Drugs acting centrally on appetite and energy regulation -- 1.1 Drugs acting on satiety -- 1.2 Drugs acting on appetite through unknown mechanisms -- 1.3 Drugs acting centrally which may or may not reduce food intake -- 2. Drugs acting peripherally -- 2.1 Blockade of digestion and absorption -- 2.2 Peripheral satiety signaling hormones -- 2.3 Drugs which stimulate energy expenditure -- 3. Summary -- Acknowledgements -- References -- Index.