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Human Recombinant TNF Suppresses Lipoprotein Lipase Activity and Stimulates Lipolysis in 3T3-L1 Cells1
Abstract
Tumor necrosis factor (TNF) has been reported to be identical to "cachectin," a monokine which we have previously proposed as a mediator of the enhanced catabolism observed in patients or animals responding to various invasive stimuli such as infections. Detailed quantitative studies were conducted on the effects of TNF on fatty acid metabolism in 3T3-L1 cells in order to explore the extent of the catabolic effects exerted by TNF compared with those by the crude cachectin. 3T3-L1 adipocytes responded to recombinant human TNF, showing a decrease in LPL activity and an increase in intracellular lipolysis. When TNF in the crude cachectin preparation was completely neutralized with anti-TNF antibody, about 75% of LPL suppression activity in the crude cachectin was absorbed, indicating that most of the mediator responsible for LPL suppression in the crude preparation is TNF. In contrast to the above effect on LPL, TNF markedly increased the lipolysis of stored fat in the cells. The effect on LPL was observed as early as 2 h after the addition of TNF, but enhancement of lipolysis required a time lag of at least 3 h before any increase of glycerol release became apparent. The effective concentrations of TNF for the stimulation of lipolysis were much higher (2.5 to 49 nM) than those for LPL suppression (50 pM to 50 nM), but both were in the same range as the concentration required for tumoricidal effect. These results demonstrate that cachectin is synonymous with TNF and that it plays an important role in the pathophysiology of deranged lipid metabolism through both suppression of LPL and enhancement of lipolysis in patients coping with invasive conditions such as infections.
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Increased levels of TNF-α and TWEAK inhibit expression of anabolism hormones such as insulin and IGF-1.
“Increased levels of TNF‐α and TWEAK have been shown to inhibit the expression of anabolism hormones such as insulin and insulin growth factor 1 (IGF‐1).[ 70 ]”
From Pathogenesis of sarcopenia and the relationship with fat mass: descriptive review (2022) · cites this paper as [70]
Pro-inflammatory cytokines TNFα and IL-1β blunt local IGF-1 expression, leading to impairment of glucose disposal into muscle and resistance of mTORC1 activation from IRS1 phosphorylation and downstream cascade.
“Additionally, the local expression of IGF‐1 is blunted by pro‐inflammatory cytokines TNFα and IL‐1β, leading to impairment of glucose disposal into the muscle and the resistance of mTORC1 activation from insulin receptor substrate 1 (IRS1) phosphorylation and its downstream cascade, an example of the synergy between IR and anabolic resistance.[ 70 ]”
From Pathogenesis of sarcopenia and the relationship with fat mass: descriptive review (2022) · cites this paper as [70]
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Metadata
- Authors
- KAWAKAMI, M., MURASE, T., OGAMA, H., ISHIBASHI, S., MORI, N., TAKAKU, F., & SHIBATA, S.
- Affiliations
- Tokyo Medical Center (JP)
- The University of Tokyo (JP)
- Venue
- The Journal of Biochemistry
- Publisher
- Oxford University Press (OUP)
- Published
- 1987-02
- Volume
- 101
- Issue
- 2
- Pages
- 331-338
- ISSN
- 0021-924X (ISSN-L)
- 1756-2651
- OpenAlex
- W2177671852
- Cited by
- 183
- References
- 0
- Citations by year
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- FWCI
- 8.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- TNF-α, lipoprotein lipase, lipolysis, 3T3-L1 adipocytes, fatty acid metabolism, lipid degradation, glycerol release
- MeSH terms
- Adipose Tissue, Animals, Antibodies, Cell Line, Cell Survival, Fatty Acids, Glycoproteins, Humans, Interleukin-1, Lipolysis, Lipoprotein Lipase, Recombinant Proteins, Tumor Necrosis Factor-alpha
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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