Evidence for a role of tumor necrosis factor α in disturbances of triglyceride and glucose metabolism predisposing to coronary heart disease

Elevated plasma levels of triglyceride-rich lipoproteins, a decreased high-density lipoprotein (HDL) cholesterol concentration, hyperinsulinemia, and impaired fibrinolytic function frequently aggregate in patients with premature coronary heart disease (CHD). Experimental studies suggest that the cytokine tumor necrosis factor alpha (TNF alpha) produced by adipocytes plays a part in the regulation of triglyceride and glucose metabolism. The present study examined whether TMF alpha is implicated in these metabolic and fibrinolytic disturbances in young postinfarction patients. TNFa levels were determined in two groups of young (age <45 years) male postinfarction patients (n = 92 and 60) and in matched, population-based control subjects (n = 63), Plasma TNF alpha was higher in patients than in controls (4.1 +/- 1.6 v 2.5 +/- 0.4 pg/mL, P < .0001). In hyperlipidemic patients, TNF alpha levels correlated significantly with the concentrations of very-low-density lipoprotein (VLDL) triglyceride and cholesterol and negatively with HDL cholesterol. Treatment with bezafibrate decreased VLDL triglycerides and increased HDL cholesterol, but did not affect TNF alpha levels. The TNF alpha concentration also correlated significantly with fasting glucose and proinsulin concentrations, as well as glucose and proinsulin levels after glucose ingestion. In contrast, no relations were found with the insulin level or degree of insulin resistance. The present results provide clinical evidence for a basic role of TNF alpha in hypertriglyceridemia, glucose intolerance, and the etiology of premature CHD. Copyright (C) 1998 by W.B. Saunders Company.