Hyperglycemia-induced production of acute phase reactants in adipose tissue

Chronic elevation of systemic levels of acute phase reactants and inflammat ory cytokines found in patients with diabetes and the often-associated meta bolic syndrome X (hypertriglyceridemia, low serum high density lipoprotein cholesterol, hypertension, and accelerated atherosclerosis) may be responsi ble for the increased incidence of cardiovascular problems in this populati on. Here we examine the contribution of adipose tissue to the systemic elev ation of acute phase reactants associated with chronic hyperglycemia. We de monstrate that adipose tissue expresses a number of acute phase reactants a t high levels, including serum amyloid A3 (SAA3), alpha1-acid glycoprotein, the lipocalin 24p3 as well as plasminogen activator inhibitor-1 (PAI-1). A dditionally, we show SAA3 is expressed at low levels under normal condition s but in the diabetic state is dramatically up-regulated in adipose tissue while down-regulated in liver. Furthermore, pro-inflammatory stimuli and hi gh glucose can lead to the induction of SAA3 in adipose tissue in vivo as w ell as in the 3T3-L1 adipocyte cell line. Adipose tissue may therefore play a major role in the pathogenic sequelae of Type II diabetes, in particular the cardiovascular problems associated with prolonged hyperglycemia.