CONTEXT: 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. SUBJECTS AND METHODS: Using a randomized controlled, crossover design, healthy young male individuals (n = 10) receivedrecombinant 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. CONCLUSION: This study demonstrates that a relatively low dose of rhTNF-alpha induces systemic lipolysis and that the skeletal muscle fat metabolism is unaffected.
RCT Entities:
CONTEXT: 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. SUBJECTS AND 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. CONCLUSION: This study demonstrates that a relatively low dose of rhTNF-alpha induces systemic lipolysis and that the skeletal muscle fat metabolism is unaffected.
Authors: Margaret Chui Ling Tse; Oana Herlea-Pana; Daniel Brobst; Xiuying Yang; John Wood; Xiang Hu; Zhixue Liu; Chi Wai Lee; Aung Moe Zaw; Billy K C Chow; Keqiang Ye; Chi Bun Chan Journal: Diabetes Date: 2017-04-12 Impact factor: 9.461
Authors: Nathan A Stephens; Richard J E Skipworth; Alisdair J Macdonald; Carolyn A Greig; James A Ross; Kenneth C H Fearon Journal: J Cachexia Sarcopenia Muscle Date: 2011-05-31 Impact factor: 12.910
Authors: N V Batista; R V S Pereira; M L M Noviello; L P A Dourado; D A Perez; G Foureaux; A J Ferreira; A V M Ferreira; D C Cara Journal: Clin Exp Immunol Date: 2014-12 Impact factor: 4.330
Authors: Christina Wu; Soledad A Fernandez; Tamara Criswell; Tarek A Chidiac; Denis Guttridge; Miguel Villalona-Calero; Tanios S Bekaii-Saab Journal: Pancreas Date: 2013-07 Impact factor: 3.327