Introduction To Adipose Tissue
Adipose tissue (AT) is composed of adipocytes and a diverse population of nonadipocytes that are commonly referred to as stromal-vascular cells (SVC). Adipose tissue has traditionally been considered a passive storage energy depot that serves as a long-term reservoir for fuel stored as triglyceride. However, laboratory, clinical, and epidemiological studies over the past decade have redefined and greatly expanded our understanding of the physiological role of AT. We now appreciate that AT is an endocrine organ with important roles in maintaining whole-body energy homeostasis and systemic metabolism. This appreciation derives in large part from the identification of multiple AT-secreted factors that modulate central and peripheral processes. These include free fatty acids (FFA), which have significant effects on glucose and insulin homeostasis, as well as bioactive peptides termed adipokines. Adipokines act in an autocrine, paracrine, and/or endocrine fashion to promote metabolic homeostasis, and integrate adipose tissue, liver, muscle, and CNS physiology.
There are currently more than 50 known adipokines, as well as locally generated hormones and metabolites that, together, affect multiple physiological functions including food intake, glucose homeostasis, lipid metabolism, inflammation, vascular tone, and angiogenesis (Fig. 1) (1). Because they affect such diverse and important processes, regulation of adipokine secretion from AT is critically important to regulating systemic metabolism. Notably, increased AT mass (as in obesity) induces characteristic qualitative and quantitative changes in adipose tissue metabolism and adipokine secretion. These changes are now implicated in the development of metabolic syndrome and its progression to more severe obesity-associated pathologies, including type 2 diabetes and cardiovascular disease.
The goal of this chapter is to provide the practicing physician with an overview of clinically relevant adipokines, the pathophysiological impacts of their dysregulation in obesity, and current therapies directed at ameliorating this dysregulation and/or its sequelae.
Before describing the specific actions of adipokines, it is important to understand that adipocytes have an active role in modulating normal health. Our understanding of the role of adipocytes in maintaining normal metabolism was enhanced by a series of elegant experiments that utilized mice that were genetically engineered to not express adipocytes. These fatless, or lipoatrophic, mice were found to have elevated circulating levels of fatty acids, hyperglycemia, and hypertriglyceridemia. Additional abnormalites included increased hyperglycemia and insulin resistance (2). Remarkably, transplantation of adipocytes back into the lipoatrophic mice normalized many of these metabolic parameters. These observations could be explained by the fact that adipocytes serve as a reservoir of fatty acids and/or secrete hormones that modulate systemic metabolism.