This text emphasizes the molecular regulation of lipid biogenesis in the context of adipocyte metabolism, differentiation, gene expression, hormone and growth signaling. Many disciplines such as genetics, cell biology and biochemistry are merging to provide a more detailed understanding of the dyamnic role that the fat cell plays in metabolism, disease and signaling.
Signal transduction comprises the intracellular biochemical signals which induce the appropriate cell response to an external stimulus. The players in signal transduction are diverse, from small molecules as first messengers, to proteins, receptors, transcription factors, among many others. The different signaling pathways and the crosstalk between them originates the unique signaling profile of every cell type in the human body. The cell signaling specificity depends on several aspects including protein composition, subcellular localization and complexes and gene promoters. This textbook provides a comprehensive overview of the specific signaling pathways on a variety of human tissues. This information can be of great value for health science researchers, professionals and students to understand key pathways for tissue-specific functions in the plethora of signals, signals receptors, transducers and effectors. Chapter 3 and 15 are available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.
This timely and most comprehensive reference available on the topic covers all the different aspects vital in the fight against the global obesity epidemic. Following a look at adipose tissue development and morphology, the authors go on to examine its metabolic and endocrine functions and its role in disease. The final section deals with comparative and evolutionary aspects of the tissue. The result is an essential resource for cell and molecular biologists, physiologists, biochemists, pharmacologists, and those working in the pharmaceutical industry.
This book is designed to provide a comprehensive insight into current perspectives and challenges in adipose tissue biology. In Adipose Tissue Biology, scientists and clinicians discuss adipocyte precursors, differentiation and growth, brown and white adipose tissue, gender, inflammation, dietary and genetic determinants of fat mass, together with evolutionary and developmental aspects of adiposity.
Obesity is a disease of society and economic transition spreading at an epidemic pace throughout the world. According to the World Health Organization, obesity is defined as an increased or abnormal accumulation of body fat mass to the extent that individual’s health will be negatively affected. Overweight is thus being considered as top at risk condition in the world and it is mandatory to identify the physiopathological causes involved in adipose tissue enlargement and related metabolic and cardiovascular health disorders.This volume provides the most up to date insights into the biology of a complex endocrine organ: the adipose tissue.
Hormonal Signaling in Biology and Medicine: Comprehensive Modern Endocrinology covers the endocrine secretions produced by every organ. This extensive collection of knowledge is organized by tissue, addressing how certain hormones are synthesized in multiple tissues, along with their structure, function and pathways, which are very applicable for researchers in drug design who need to focus on a specific step along the pathway. This is a must have reference for researchers in endocrinology and practicing endocrinologists, but it is also ideal for biochemists, pharmacologists, biologists and students. Serves as a valuable desk reference for researchers Provides information on the structure of a given hormone, its receptor(s), and the pathways that become activated Includes extensive citations to the literature that will enable the reader to dig more deeply into the effects of a given hormone
The world is faced with an epidemic of metabolic diseases such as obesity and type 2 diabetes. This is due to changes in dietary habits and the decrease in physical activity. Exercise is usually part of the prescription, the first line of defense, to prevent or treat metabolic disorders. However, we are still learning how and why exercise provides metabolic benefits in human health. This open access volume focuses on the cellular and molecular pathways that link exercise, muscle biology, hormones and metabolism. This will include novel “myokines” that might act as new therapeutic agents in the future.
The family of "stress" peptides that includes CRH and UCNs are emerging as important regulators of the homeostatic mechanisms regulating energy balance and metabolism. These peptides exert well documented central anorectic and thermogenic actions in controlling food uptake and optimise energy losses. Furthermore, CRH acting through specific G-protein coupled receptors, CRH-R1 and R2 can target multiple peripheral tissues such as skeletal muscle and adipose tissue to influence important metabolic pathways. Two types of adipose tissue exist in mammals: WAT and BAT. Since WAT is the largest energy reserve in mammals and BAT can utilize energy through adaptive thermogenesis, one of the goals in this study was to identify the presence of CRH system components in adipose tissue. Real time RT-PCR and immunofluorescence demonstrated that CRH-Rs as well as CRH, UCN-I, and UCN-II are expressed in both WAT and BAT, raising the possibility that CRH and UCNs are important regulators of energy storage and adaptive thermogenesis. Also the functional roles of CRH-Rs in adipose tissue were investigated. Using an experimental paradigm the T37i fibroblast that can differentiate into brown adipocyte, it was demonstrated that CRH at low (nanomolar) but not high (submicromolar) concentrations stimulated a signaling pathway involving the AC/cAMP/PKA/AMPK signaling cascade that regulates downstream phosphorylation of HSL. This was associated with a significant translocation of HSL toward lipid droplets and association with perilipin, as demonstrated with immunofluorescence. Studies applying quantitative RT-PCR also suggested that CRH-R1 appears to regulate genes important for adaptive thermogenesis, whereas CRH-R2 likely regulates brown adipocyte formation. Further analysis using an experimental paradigm the 3T3L1 fibroblast that can differentiate into white adipocyte showed that exposure of 3T3L1 cells to UCN-II (a specific CRH-R2 agonist) or NBI-27914 (a CRH-R1 specific antagonist) were able to induce morphological and biochemical characteristics suggesting adipocyte differentiation to a "beige" phenotype in white preadipocytes/adipocytes. Thus, CRH-R1 and R2 could be of potential importance in maintenance of energy homeostasis. Moreover, in vivo analysis showed that CRH system seems to demonstrate a certain degree of plasticity in response to stress perturbation. For instance, HFD significantly repressed the expression of CRH-Rs and their agonists, whereas food deprivation dramatically increased their expression. The analysis of quantitative RTPCR demonstrated that this activation of CRH system might be associated with induction of 'beige' cells in white fat depots. Since CRH-R1 KO mice displayed a lean phenotype and resistance to HFD-induced fat accumulation and these phenotypes can be reversed by supplementation of corticosterone, role of CRH-R2 in adipose tissue of these KO mice was investigated. Data showed that CRH-R2 activation likely induced BAT activity and transdifferentiation from WAT to BAT in CRH-R1 KO mice. Corticosterone reversed these changes in KO mice via potential suppression of CRH-R2.
The Endoplasmic Reticulum (ER) is an organelle with extraordinary signaling and homeostatic functions. It is the organelle responsible for protein folding, maturation, quality control and trafficking of proteins destined for the plasma membrane or for secretion into the extracellular environment. Failure, overloading or malfunctioning of any of the signaling or quality control mechanisms occurring in the ER may provoke a stress condition known as ‘ER stress’. Accumulating evidence indicates that ER stress may dramatically perturb interactions between the cell and its environment, and contribute to the development of human diseases, ranging from metabolic diseases and cancer to neurodegenerative diseases, or impact therapeutic outcome. This book primarily focuses on the pathophysiology of ER stress. It introduces the molecular bases of ER stress, the emerging relevance of the ER-mitochondria cross-talk, the signaling pathways engaged and cellular responses to ER stress, including the adaptive Unfolded Protein Response (UPR), autophagy as well as cell death. Next the book addresses the role of ER stress in physiology and in the etiology of relevant pathological conditions, like carcinogenesis and inflammation, neurodegeneration and metabolic disease. The last chapter describes how ER stress pathways can be targeted for therapeutic benefit. Altogether, this book will provide the reader with an exhaustive view of ER stress biology and the latest insights in the role of ER stress in relevant human diseases.
