Adipose Tissue and Adipokines in Health and Disease

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Adipose Tissue and Insulin Resistance (p. 281-282)

Stephen E. Borst

21 Abstract

Adiposity, especially visceral adiposity, is an important risk factor for the development of insulin resistance and type 2 diabetes. In addition to its role in storing energy, adipose tissue also secretes into the circulation a number of hormones and other factors that can alter the response to insulin in distant tissues, such as liver and muscle. Many of these factors are cytokines, which have been associated with the immune system.

Fat-derived hormones that can enhance insulin signaling include leptin, adiponectin, and possibly visfatin. Those impairing insulin signaling include tumor necrosis factor- , resistin, and several of the interleukins. Obesity has also been identified as a low-grade inflammatory state. Several possible mechanisms are discussed whereby rapid growth of adipose tissue might trigger a local inflammatory response. It is suggested that this inflammatory response and associated release of cytokines may constitute the link between obesity and insulin resistance.

Key Words: Tumor necrosis factor, resistin, adiponectin, interleukins, free fatty acids, subcutaneous fat, visceral fat, insulin signaling.

INTRODUCTION

Obesity and type 2 diabetes are the most common metabolic diseases in Western society, together affecting as much as half of the adult population (1). Not only is the prevalence of these conditions high, but it also continues to increase. Insulin resistance a prediabetic condition, characterized by a failure of target organs to respond normally to insulin. Insulin resistance includes a central component (incomplete suppression of hepatic glucose output) and a peripheral component (impaired insulin-mediated glucose uptake in skeletal muscle and adipose tissue) (2). When increased insulin secretion is no longer sufficient to prevent hyperglycemia, the subject progresses from insulin resistance to type 2 diabetes. Insulin resistance is associated with other conditions such as central obesity, hypertension, and dyslipidemia, all risk factors for cardiovascular disease. The constellation of these metabolic abnormalities has been termed metabolic syndrome.

Obesity is a well-recognized risk factor for the development of insulin resistance and metabolic syndrome. In addition to the total amount of fat, distribution of adipose tissue also important, with most studies concluding that visceral fat contributes considerably more to insulin resistance than does subcutaneous fat (3). However, one report, by Misra al., documented a robust correlation between posterior abdominal subcutaneous fat and insulin resistance (4). Underscoring the importance of visceral fat is the report by Klein et al. that liposuction, resulting in a substantial reduction of subcutaneous fat, did not enhance insulin responsiveness in insulin-resistant subjects (5). In rats, we (6) and others (7) have found that surgical removal of visceral fat reverses insulin resistance.

Traditionally, adipose tissue has been regarded largely as a depot for stored fat. More recently, it has become clear that adipose tissue plays an active role in energy metabolism and is the source of hormones, cytokines, and metabolites that play an important role in whole-body metabolism (8). The role of these substances may be either autocrine or endocrine. Adipose tissue, especially visceral fat, is the source of a number of substances that might play a role in the development of insulin resistance. Among the latter are tumor necrosis factor (TNF)- , adiponectin, interleukin (IL)-6, resistin, and free fatty acids. The difference in the metabolic effects of visceral versus subcutaneous fat may be attributed both to differences in the hormones secreted by the two types of fat and to the fact that hormones secreted by visceral fat reach the liver in high concentration. The latter is due to the fact that visceral fat drains into the portal circulation, whereas subcutaneous fat drains into the systemic circulation (8). This review will focus on the regulation of insulin responsiveness by adipokines and on evidence supporting the hypothesis that these hormones play a role in the pathophysiology of insulin resistance.