Tumor Necrosis Factor-α Modulates Human in Vivo Lipolysis
Abstract
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.
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TNF-α infusion increases whole-body lipolysis by 40% with a concomitant increase in FFA clearance, but with no changes in skeletal muscle FFA uptake, release, or oxidation.
“Moreover, it was recently demonstrated that TNF-alpha infusion increases whole-body lipolysis by 40% with a concomitant increase in FFA clearance, but with no changes in skeletal muscle FFA uptake, release, or oxidation [45].”
From Exercise as a Mean to Control Low‐Grade Systemic Inflammation (2008) · cites this paper as [45]
Findings on TNF effects on both glucose and fat metabolism provide a direct molecular link between low-grade systemic inflammation and the metabolic syndrome.
“The findings with regard to an effect of TNF on both glucose and fat metabolism provide a direct molecular link between low-grade systemic inflammation and the metabolic syndrome [44, 45].”
From Exercise as a Mean to Control Low‐Grade Systemic Inflammation (2008) · cites this paper as [45]
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Self-citation
- Authors
- Plomgaard, P., Fischer, C. P., Ibfelt, T., Pedersen, B. K., & van Hall, G.
- Affiliations
- University of Copenhagen (DK)
- Copenhagen Muscle Research Centre (P.P., C.P.F., T.I., G.v.H.), Rigshospitalet, 2400 Copenhagen, Denmark
- Corresponding author
- Plomgaard, Peter
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2008-02-01
- Volume
- 93
- Issue
- 2
- Pages
- 543-549
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2057628895
- Cited by
- 97
- References
- 42
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 4 · 2023: 3 · 2022: 2 · 2021: 3 · 2018: 5 · 2017: 5 · 2016: 4 · 2015: 5 · 2014: 12 · 2013: 9 · 2012: 10
- FWCI
- 3.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- National Research Foundation
- Danmarks Grundforskningsfond (02-512-555, DG 02–512‐555)
- Rigshospitalet
- Novo Nordisk Fonden
- Diabetesforeningen
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- TNF-α, lipolysis, hyperlipidemia, low-grade inflammation, interleukin-6, energy metabolism, glucose turnover
- MeSH terms
- Adult, Blood Glucose, Energy Metabolism, Humans, Lactates, Male, Palmitates, Recombinant Proteins, Tumor Necrosis Factor-alpha, Interleukin-6, Muscle, Skeletal, Cross-Over Studies, Lipid Metabolism
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