Encyclopedia of Molecular Cell Biology and Molecular Medicine, Volume 16:

Book Preface

Although the physiology of adipose tissue and the molecular and cellular biology of the adipocyte have been subjects of research interest for many years, new work in this area has transformed our understanding of the adipocyte and its role in regulating human physiology. We now recognize that in addition to its long appreciated function as a lipid storage depot, the adipocyte plays a much more active role in regulating whole body fuel partitioning and metabolism. The growing interest in the physiology of adipose tissue and the role that it plays in metabolic regulation is fueled to a large degree by the realization that we are in the midst of a growing epidemic of the metabolic disorders of diabetes and obesity. In most developed countries, the incidence of both of these diseases has increased dramatically in the past few decades. Currently (as of 2003), there are 16 million diabetics in the United States, and the incidence of the disease has increased by 49% from 1990 to 2000, with projections indicating a 165% increase by 2050. There has also been a dramatic increase in the incidence of obesity, with over one-third of the population in the United States now classified as obese. Although the causal relationship between diabetes and obesity is not fully understood, a likely common link is the adipocyte.

In healthy individuals, excess fat is stored in adipocytes while only low amounts of triglyceride are maintained in nonadipocytes. It is thought that in obese individuals, the capacity for adipose tissue to accommodate excess lipid is exceeded, resulting in the abnormal accumulation of lipid in other tissues. This elevation in intracellular triglyceride content has been associated with physiological dysfunction (lipotoxicity) that contributes to the development of obesity-related type 2 diabetes. This pathological accumulation of lipid in nonadipose tissue may be the result of a physiological dysfunction of the adipocyte that is induced by the obese state. In this chapter, we will review the current state of knowledge about fat cell lipid metabolism, and how adipocytes function to balance storage and mobilization to meet the energetic demands of the organism without exposing nonadipose tissues to deleterious fat accumulation.

In addition to its function as an energystorage depot, we now understand that adipose tissue is also a bona fide endocrine organ, secreting hormones that regulate fat metabolism in other tissues throughout the body. The list of biologically active peptides known to be secreted by fat cells has grown significantly in recent years, and although the physiological function of most of these adipocyte-derived hormones (adipokines) is not fully understood, it is clear that they are important components of the physiological system that controls lipid storage, distribution, and utilization throughout the body. Our current knowledge of the regulation of adipokine production and their downstream metabolic effects is reviewed below. Our increased understanding of the active role that adipocytes play in regulating metabolism has stimulated a growing interest in adipose tissue as a therapeutic target for new agents to treat diabetes,obesity, and other metabolic diseases. The underlying assumption for this effort is that drugs acting on adipocyte lipid metabolism parameters or on hormone production pathways could have beneficial effects on metabolic abnormalities of diabetes and obesity. In support of this possibility are recent findings, which are reviewed below, demonstrating that an important family of antidiabetic drugs acts, at least in part, by modulating adipocyte physiology. A complete understanding of the medical significance of the adipocyte will require a comprehensive knowledge of the development of adipocytes and adipose tissue, of molecular biology and physiology of mature adipocyte, as well as the interaction of adipose tissue with the broader regulatory systems that control the whole body energy balance and fuel partitioning.vvv