Verlag:
Springer International Publishing AG, Cham
Twenty years after its discovery, recombinant human leptin has been approved by the Food and Drug Administration for the treatment of patients with lipodystrophy. Beginning with a synthesis of the vast body of work on its discovery, dissection of...
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Universität Ulm, Kommunikations- und Informationszentrum, Bibliotheksservices
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Twenty years after its discovery, recombinant human leptin has been approved by the Food and Drug Administration for the treatment of patients with lipodystrophy. Beginning with a synthesis of the vast body of work on its discovery, dissection of mechanisms, and effects in experimental models , the focus of this book shifts to a consideration of the regulation and role of leptin in humans. The emphasis on human-level data is a unique feature of this book. The results of numerous studies indicate that leptin is indeed a regulated human hormone. Leptin provides a detailed account of the myriad physiological, hormonal, metabolic, immunological, mitogenic and inflammatory modulators and targets of leptin in a single volume. Next follows a comprehensive presentation of the therapeutic trials of recombinant leptin in patients with congenital leptin deficiency, lipodystrophy, hypothalamic amenorrhea, and other emerging areas, including leptin supplementation in leptin-replete subjects, leptin substitution for insulin in diabetic models, and novel combination regimens of leptin and other biogenic peptides. Unanswered questions and future directions in leptin research are highlighted in the Foreword by Dr. Jeffrey Friedman and throughout the volume. Identifying such questions helps direct research that could deepen understanding of the complex regulation of leptin under physiological and pathological conditions, a critical prerequisite to its rational deployment in the treatment of human disorders. Intro -- Foreword -- Background -- Wiring Diagram of a Complex Behavior -- Obesity Has a Substantial Genetic Component -- Leptin Deficiency -- Leptin Resistance -- Questions for the Future -- References -- Preface -- Contents -- Contributors -- 1: Discovery of Leptin and Elucidation of Leptin Gene Expression -- The Milieu Intérieur and Homeostasis -- VMH Lesions and the Controller System -- Douglas Coleman and Parabiosis -- Molecular Genetics: A Novel Approach to Identify the ob Gene -- Reverse Genetics and Positional Cloning -- Genetic Mapping -- Physical Mapping of the ob Gene -- Ob Gene Identification -- Elucidation of ob Gene Expression and Bioactivity -- Conclusions -- References -- 2: Leptin Receptors and Mechanism of Action -- Introduction -- LEPR Structure and Mechanism of Action -- LEPR Genomic Organization -- LEPR Isoforms -- LEPR Mechanisms of Action -- Cell Surface Localization -- Activation -- Signaling Pathways -- Genetic Abnormalities in Human LEPR -- Mutations in LEPR -- Clinical Consequences of LEPR Homozygous Mutations -- Management of Patients -- References -- 3: Leptin Interaction with Brain Orexigenic and Anorexigenic Pathways -- Introduction -- Leptin and the Brain -- Leptin Receptors in the CNS -- Leptin Actions on Hypothalamic Neurons -- Neuronal Responses to Leptin -- Connections of Leptin Target Neurons -- Interaction of Leptin with Satiety Signals -- Leptin Sensitive Pathways for Regulation of Energy Expenditure -- CNS Leptin Resistance and Obesity -- CNS Leptin Action and Diabetes -- Leptin Actions in Human Brain -- References -- 4: Measurement of Circulating Leptin and Soluble Leptin Receptors -- Introduction -- Measurement of Circulating Leptin -- Measurement of Soluble Leptin Receptor -- Summary and Conclusions -- References -- 5: Physiological and Hormonal Factors that Influence Leptin Production -- Introduction.