Tumor Necrosis Factor-α Modulates Humanin VivoLipolysis

Abstract

Context: Low-grade systemic inflammation is a feature of most lifestyle-related chronic diseases. Enhanced TNF-α concentrations have been implicated in the development of hyperlipidemia. Objective: We hypothesized that an acute elevation of TNF-α in plasma would cause an increase in lipolysis, increasing circulatory free fatty acid (FFA) levels. Subjects and Methods: Using a randomized controlled, crossover design, healthy young male individuals (n = 10) received recombinant human (rh) TNF-α (700 ng/m⁻²·h⁻¹) for 4 h, and energy metabolism was evaluated using a combination of tracer dilution methodology and arterial-venous differences over the leg. Results: Plasma TNF-α levels increased from 0.7 ± 0.04 to 16.7 ± 1.8 pg/ml, and plasma IL-6 increased from 1.0 ± 0.2 to 9.2 ± 1.0 pg/ml (P < 0.05) after 4-h rhTNF-α infusion. Here, we demonstrate that 4-h rhTNF-α infusion increases whole body lipolysis by 40% (P < 0.05) with a concomitant increase in FFA clearance, with no changes in skeletal muscle FFA uptake, release, or oxidation. Of note, systemic glucose turnover and lactate and catecholamine levels were unaffected by rhTNF-α infusion. Conclusion: This study demonstrates that a relatively low dose of rhTNF-α induces systemic lipolysis and that the skeletal muscle fat metabolism is unaffected.