Insulin Resistance in States of Energy Excess: Underlying Pathophysiological Concepts

Abstract

KEY POINTS The epidemic of obesity and associated metabolic and cardiovascular disorders are of increasing prevalence and, thus, importance. Despite significant progress made during this past decade, the pathophysiological mechanisms underlying the development of these diseases are still poorly understood. A dysfunctional adipose tissue is currently considered the "conditio sine qua non" for the development of the metabolic syndrome; this may result front either an a priori limited or an exhausted storage capacity of adipocytes in states of lipoatrophy or chronic energy excess, respectively. The latter is associated with hypertrophy of adipocytes and when coupled with excessive fat deposition in muscle and liver leads to a derangement in the release of fatty acids, hormones, adipokines, proinflammatory cytokines, and other molecules, which, in turn, result in insulin resistance and a low grade inflammation. According to our current understanding, chronic inflammation may contribute further toward the development of both insulin resistance and artherosclerosis. Impairment of insulin action in the periphery and activation of certain immunological responses lead over time to the special features and comorbidites of the metabolic syndrome. This chapter provides information on factors and molecules involved in the pathogenesis of insulin resistance and other aspects of the metabolic syndrome and discusses our present understanding of the role adipokines, free fatty acids, and inflammatory markers play in the development of this syndrome.