Tumor necrosis factor-alpha modulates human in vivo lipolysis.
BACKGROUND
Low-grade systemic inflammation is a feature of most lifestyle-related chronic diseases. Enhanced TNF-alpha concentrations have been implicated in the development of hyperlipidemia.


OBJECTIVE
We hypothesized that an acute elevation of TNF-alpha in plasma would cause an increase in lipolysis, increasing circulatory free fatty acid (FFA) levels.


METHODS
Using a randomized controlled, crossover design, healthy young male individuals (n = 10) received recombinant human (rh) TNF-alpha (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-alpha 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-alpha infusion. Here, we demonstrate that 4-h rhTNF-alpha 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-alpha infusion.


CONCLUSIONS
This study demonstrates that a relatively low dose of rhTNF-alpha induces systemic lipolysis and that the skeletal muscle fat metabolism is unaffected.
Plomgaard
Peter
P
Centre of Inflammation and Metabolism, Department of Infectious Diseases, Faculty of Health Sciences, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark. plomgaard@dadlnet.dk
Fischer
Christian P
CP
Ibfelt
Tobias
T
Pedersen
Bente K
BK
van Hall
Gerrit
G
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D018592:Cross-Over Studies; D004734:Energy Metabolism / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D007773:Lactates / Q000097:blood; D050356:Lipid Metabolism / Q000187:drug effects*; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D010168:Palmitates / Q000097:blood; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000494:pharmacology*
D001786:Blood Glucose; D015850:Interleukin-6; D007773:Lactates; D010168:Palmitates; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha