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Cited by 434

The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.

Tumor Necrosis Factor-α Stimulates Lipolysis in Differentiated Human Adipocytes Through Activation of Extracellular Signal-Related Kinase and Elevation of Intracellular cAMP

Open access
Zhang, Hui H., Halbleib, Melanie, Ahmad, Faiyaz, Manganiello, Vincent C., Greenberg, Andrew S.·2002·Diabetes
DOI 10.2337/diabetes.51.10.2929
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Abstract

Tumor necrosis factor-α (TNF-α) stimulates lipolysis in human adipocytes. However, the mechanisms regulating this process are largely unknown. We demonstrate that TNF-α increases lipolysis in differentiated human adipocytes by activation of mitogen-activated protein kinase kinase (MEK), extracellular signal-related kinase (ERK), and elevation of intracellular cAMP. TNF-α activated ERK and increased lipolysis; these effects were inhibited by two specific MEK inhibitors, PD98059 and U0126. TNF-α treatment caused an electrophoretic shift of perilipin from 65 to 67 kDa, consistent with perilipin hyperphosphorylation by activated cAMP-dependent protein kinase A (PKA). Coincubation with TNF-α and MEK inhibitors caused perilipin to migrate as a single 65-kDa band. Consistent with the hypothesis that TNF-α induces perilipin hyperphosphorylation by activating PKA, TNF-α increased intracellular cAMP ∼1.7-fold, and the increase was abrogated by PD98059. Furthermore, H89, a specific PKA inhibitor, blocked TNF-α-induced lipolysis and the electrophoretic shift of perilipin, suggesting a role for PKA in TNF-α-induced lipolysis. Finally, TNF-α decreased the expression of cyclic-nucleotide phosphodiesterase 3B (PDE3B) by ∼50%, delineating a mechanism by which TNF-α could increase intracellular cAMP. Cotreatment with PD98059 restored PDE3B expression. These studies suggest that in human adipocytes, TNF-α stimulates lipolysis through activation of MEK-ERK and subsequent increase in intracellular cAMP.

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Metadata

Authors
Zhang, H. H., Halbleib, M., Ahmad, F., Manganiello, V. C., & Greenberg, A. S.
Venue
Diabetes
Publisher
American Diabetes Association
Published
2002-10-01
Volume
51
Issue
10
Pages
2929-2935
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
DOI
10.2337/diabetes.51.10.2929
OpenAlex
W2161012482
Cited by
434
References
41
FWCI
6.36
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Tumor Necrosis Factor-α Stimulates Lipolysis in Differentiated Human Adipocytes Through Activation of Extracellular Signal-Related Kinase and Elevation of Intracellular cAMP. https://app.cochat.ai/papers/10.2337/diabetes.51.10.2929
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Zhang, H. H., Halbleib, M., Ahmad, F., Manganiello, V. C., & Greenberg, A. S. (2002). Tumor Necrosis Factor-α Stimulates Lipolysis in Differentiated Human Adipocytes Through Activation of Extracellular Signal-Related Kinase and Elevation of Intracellular cAMP. Diabetes. https://doi.org/10.2337/diabetes.51.10.2929

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Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.