Context: Low-grade systemic inflammation is a feature of most lifestyle-related chronic diseases. Enhanced tumor necrosis factor alpha (TNF-) concentrations have been implicated in the development of hyperlipidemia.

Objective: We hypothesized that an acute elevation of TNF- in plasma would cause an increase in lipolysis raising circulatory free fatty acid levels.

Subjects and Methods: Using a randomized controlled, crossover design healthy young male individuals (n = 10) received recombinant human (rh) TNF- (700 ng·m–2·h–1) for 4h and energy metabolism was evaluated by using a combination of tracer dilution methodology and arterials-venous differences over the leg.

Results: Plasma TNF- levels increased from 0.7 ± 0.04 to 16.7 ± 1.8 pg/ml and plasma interleukin-6 (IL-6) increased from 1.0 ± 0.2 to 9.2 ± 1.0 pg/ml (P < 0.05) after 4h of rhTNF- infusion. Here we demonstrate that 4h of rhTNF- infusion increases whole body lipolysis by 40% (P < 0.05) with a concomitant increase in free fatty acid clearance with no changes in skeletal muscle free fatty acid uptake, release or oxidation. Of note, systemic glucose turnover and lactate and catecholamine levels were unaffected by rhTNF- infusion.

Conclusion: This study demonstrates that a relatively low dose of rhTNF- induces systemic lipolysis, and that the skeletal muscle fat metabolism is unaffected.