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Characterisation of receptor-specific TNFα functions in adipocyte cell lines lacking type 1 and 2 TNF receptors

Characterisation of receptor-specific TNFα functions in adipocyte cell lines lacking type 1 and 2 TNF receptors
Characterisation of receptor-specific TNFα functions in adipocyte cell lines lacking type 1 and 2 TNF receptors

Tumour necrosis factor-alpha (TNFα) is a multifunctional cytokine that exerts a myriad of biological actions in numerous different tissues including adipocytes through its two distinct cell surface receptors. To address the role of each TNF receptor in the biological actions of TNFα in adipocytes, we have developed four new preadipocyte cell lines. These were established from wild type controls (TNFR1(+/+)R2(+/+)) and from mice lacking TNFR1 (TNFR1(-/-)), TNFR2 (TNFR2(-/-)) or both (TNFR1(-/-)R2(-/-)). All four new cell lines can fully differentiate to form mature adipocytes, under appropriate culture conditions, as judged by cell morphology, expression of multiple adipogenic markers and the ability to mediate agonist-stimulated lipolysis and insulin-stimulated glucose transport. In wild type (TNFR1(+/+)R2(+/+)) and TNFR2(-/-) adipocytes, TNFα stimulated lipolysis and inhibited insulin-stimulated glucose transport as well as insulin receptor autophosphorylation. In contrast, these activities were completely lost in the TNFR1(-/-)R2(-/-) and TNFR1(-/-) cells. Taken together, these studies demonstrate that TNFα-induced lipolysis, as well as inhibition of insulin-stimulated glucose transport are predominantly mediated by TNFR1 and that the presence of TNFR2 is not necessary for these functions. This new experimental system promises to be useful in dissecting the molecular pathways activated by each TNF receptor in mediating the biological functions of TNFα in differentiated adipocytes. Copyright (C) 2000 Federation of European Biochemical Societies.

Adipogenesis, Glucose metabolism, Insulin resistance, Lipolysis, Preadipocyte, Tumor necrosis factor receptor
0014-5793
77-82
Sethi, Jaswinder K.
923f1a81-91e4-46cd-8853-bb4a979f5a85
Xu, Haiyan
b1f0cf46-146f-4482-b9d6-d78e786c0970
Uysal, K. Teoman
c38d081e-eacc-4e12-be9b-7b76781c1ca1
Wiesbrock, Sarah M.
242444aa-498c-4dcf-93f1-d7ea86706163
Scheja, Ludger
523f527f-0c26-47a9-96f0-ec12f7789ba6
Hotamisligil, Gökhan S.
59ea0e53-a259-4224-9d24-d503c4a29d15
Sethi, Jaswinder K.
923f1a81-91e4-46cd-8853-bb4a979f5a85
Xu, Haiyan
b1f0cf46-146f-4482-b9d6-d78e786c0970
Uysal, K. Teoman
c38d081e-eacc-4e12-be9b-7b76781c1ca1
Wiesbrock, Sarah M.
242444aa-498c-4dcf-93f1-d7ea86706163
Scheja, Ludger
523f527f-0c26-47a9-96f0-ec12f7789ba6
Hotamisligil, Gökhan S.
59ea0e53-a259-4224-9d24-d503c4a29d15

Sethi, Jaswinder K., Xu, Haiyan, Uysal, K. Teoman, Wiesbrock, Sarah M., Scheja, Ludger and Hotamisligil, Gökhan S. (2000) Characterisation of receptor-specific TNFα functions in adipocyte cell lines lacking type 1 and 2 TNF receptors. FEBS Letters, 469 (1), 77-82. (doi:10.1016/S0014-5793(00)01250-3).

Record type: Article

Abstract

Tumour necrosis factor-alpha (TNFα) is a multifunctional cytokine that exerts a myriad of biological actions in numerous different tissues including adipocytes through its two distinct cell surface receptors. To address the role of each TNF receptor in the biological actions of TNFα in adipocytes, we have developed four new preadipocyte cell lines. These were established from wild type controls (TNFR1(+/+)R2(+/+)) and from mice lacking TNFR1 (TNFR1(-/-)), TNFR2 (TNFR2(-/-)) or both (TNFR1(-/-)R2(-/-)). All four new cell lines can fully differentiate to form mature adipocytes, under appropriate culture conditions, as judged by cell morphology, expression of multiple adipogenic markers and the ability to mediate agonist-stimulated lipolysis and insulin-stimulated glucose transport. In wild type (TNFR1(+/+)R2(+/+)) and TNFR2(-/-) adipocytes, TNFα stimulated lipolysis and inhibited insulin-stimulated glucose transport as well as insulin receptor autophosphorylation. In contrast, these activities were completely lost in the TNFR1(-/-)R2(-/-) and TNFR1(-/-) cells. Taken together, these studies demonstrate that TNFα-induced lipolysis, as well as inhibition of insulin-stimulated glucose transport are predominantly mediated by TNFR1 and that the presence of TNFR2 is not necessary for these functions. This new experimental system promises to be useful in dissecting the molecular pathways activated by each TNF receptor in mediating the biological functions of TNFα in differentiated adipocytes. Copyright (C) 2000 Federation of European Biochemical Societies.

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e-pub ahead of print date: 8 March 2000
Published date: March 2000
Keywords: Adipogenesis, Glucose metabolism, Insulin resistance, Lipolysis, Preadipocyte, Tumor necrosis factor receptor

Identifiers

Local EPrints ID: 415414
URI: http://eprints.soton.ac.uk/id/eprint/415414
ISSN: 0014-5793
PURE UUID: ae53e072-7f05-4c03-9d7a-cc250856e7bd
ORCID for Jaswinder K. Sethi: ORCID iD orcid.org/0000-0003-4157-0475

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Date deposited: 09 Nov 2017 17:30
Last modified: 16 Mar 2024 04:31

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Contributors

Author: Haiyan Xu
Author: K. Teoman Uysal
Author: Sarah M. Wiesbrock
Author: Ludger Scheja
Author: Gökhan S. Hotamisligil

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