Adipose tissue has active metabolic properties that contribute to the clinical effects of obesity. The contents of adipose tissue (including adipocytes, connective tissue matrix, nerve tissue, immune cells, stromovascular cells, and immune cells) work together to respond to multiple body signals by secreting factors (including leptin, other cytokines, adiponectin, complement components, plasminogen activator inhibitor-1, resistin, and proteins of the reninangiotensin system) with important endocrine functions. Metabolism of sex steroids and glucocorticoids also takes place in adipose tissue. Kershaw and Flier reviewed the endocrine functions of adipose tissue to clarify the adverse metabolic consequences of either tissue excess or deficiency.
Leptin, a polypeptide produced by adipocytes in proportion to body mass and nutritional status, is regulated by a variety of other body factors and affects hypothalamic pathways and peripheral tissue. Leptin is a signal of nutritional sufficiency and decreases in response to starvation, caloric restriction, or weight loss. Leptin levels are elevated in common forms of obesity, indicating a state of leptin resistance. Other important endocrine effects of leptin include immune function regulation, hematopoiesis, angiogenesis, and bone development.
Tumor necrosing factor α (TNFα) is a cytokine that causes tumor necrosis. Production of TNFα is increased in persons who are obese and may be related to induction of insulin resistance. Interleukin-6 is another cytokine produced by adipose tissue that has been positively correlated with obesity, impaired glucose tolerance, and insulin resistance. Concentrations of plasma levels of interleukin-6 predict risk for cardiovascular disease and type 2 diabetes. Activated macrophages that infiltrate adipose tissue in greater numbers in persons who are obese produce inflammatory factors that contribute to insulin resistance.
Plasminogen activator inhibitor-1, an inhibitor of fibrinolysis, is expressed by adipocytes and is elevated in persons who are obese and have insulin resistance. It correlates with development of the metabolic syndrome. Weight loss or treatment with insulin-sensitizer medications can reduce plasminogen activator inhibitor-1 levels. Adinopectin appears to decline before the onset of obesity or insulin resistance and increases when insulin sensitivity improves. Adinopectin appears to actually improve hepatic insulin sensitivity, reduce hepatic glucose output, and increase glucose use in the muscle. The polypeptides adipsin and resistin are positively correlated with adiposity, insulin resistance, dyslipidemia, and cardiovascular disease.
Adipose tissue produces several proteins of the renin angiotensin system including renin, angiotensin, angiotensin I, angiotensin II, and angiotensin-converting enzyme. Because angiotensin II is important in blood pressure regulation, adipose tissue production may be the link between obesity and hypertension.
Enzymes involved in the metabolism of steroid hormones and glucocorticoids also are produced in adipose tissue, having a direct effect on metabolism and secretion of sex steroids and glucocorticoids. These relationships hint at a possible role for adipose tissue in sexual dimorphism and the development of visceral obesity and the metabolic syndrome.
The authors conclude that further evaluation of the physiologic roles of adipose tissue–derived hormones may provide insight into energy homeostasis and other physiologic systems. This insight may result in better treatments for the metabolic consequences of adipose tissue excess (obesity) or deficiency.