A novel crosstalk between Alk7 and cGMP signaling differentially regulates brown adipocyte function
Objective: Obesity is an enormous burden for patients and health systems world-wide. Brown adipose tissue dissipates energy in response to cold and has been shown to be metabolically active in human adults. The type I transforming growth factor β (TGFβ) receptor Activin receptor-like kinase 7 (Alk7)...
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doaj-1e4230b53a404bb3bf756fcc5c6692eb2020-11-24T21:17:58ZengElsevierMolecular Metabolism2212-87782015-08-014857658310.1016/j.molmet.2015.06.003A novel crosstalk between Alk7 and cGMP signaling differentially regulates brown adipocyte functionAileen Balkow0Johanna Jagow1Bodo Haas2Franziska Siegel3Ana Kilić4Alexander Pfeifer5Institute of Pharmacology and Toxicology, University Hospital Bonn, University of Bonn, 53127 Bonn, GermanyInstitute of Pharmacology and Toxicology, University Hospital Bonn, University of Bonn, 53127 Bonn, GermanyInstitute of Pharmacology and Toxicology, University Hospital Bonn, University of Bonn, 53127 Bonn, GermanyInstitute of Pharmacology and Toxicology, University Hospital Bonn, University of Bonn, 53127 Bonn, GermanyInstitute of Pharmacology and Toxicology, University Hospital Bonn, University of Bonn, 53127 Bonn, GermanyInstitute of Pharmacology and Toxicology, University Hospital Bonn, University of Bonn, 53127 Bonn, GermanyObjective: Obesity is an enormous burden for patients and health systems world-wide. Brown adipose tissue dissipates energy in response to cold and has been shown to be metabolically active in human adults. The type I transforming growth factor β (TGFβ) receptor Activin receptor-like kinase 7 (Alk7) is highly expressed in adipose tissues and is down-regulated in obese patients. Here, we studied the function of Alk7 in brown adipocytes. Methods: Using pharmacological and genetic tools, Alk7 signaling pathway and its effects were studied in murine brown adipocytes. Brown adipocyte differentiation and activation was analyzed. Results: Alk7 is highly upregulated during differentiation of brown adipocytes. Interestingly, Alk7 expression is increased by cGMP/protein kinase G (PKG) signaling, which enhances brown adipocyte differentiation. Activin AB effectively activates Alk7 and SMAD3 signaling. Activation of Alk7 in brown preadipocytes suppresses the master adipogenic transcription factor PPARγ and differentiation. Stimulation of Alk7 during late differentiation of brown adipocytes reduces lipid content and adipogenic marker expression but enhances UCP1 expression. Conclusions: We found a so far unknown crosstalk between cGMP and Alk7 signaling pathways. Tight regulation of Alk7 is required for efficient differentiation of brown adipocytes. Alk7 has differential effects on adipogenic differentiation and the development of the thermogenic program in brown adipocytes.http://www.sciencedirect.com/science/article/pii/S2212877815000976Alk7cGMPBrown adipocytesUCP1Activin |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Aileen Balkow Johanna Jagow Bodo Haas Franziska Siegel Ana Kilić Alexander Pfeifer |
spellingShingle |
Aileen Balkow Johanna Jagow Bodo Haas Franziska Siegel Ana Kilić Alexander Pfeifer A novel crosstalk between Alk7 and cGMP signaling differentially regulates brown adipocyte function Molecular Metabolism Alk7 cGMP Brown adipocytes UCP1 Activin |
author_facet |
Aileen Balkow Johanna Jagow Bodo Haas Franziska Siegel Ana Kilić Alexander Pfeifer |
author_sort |
Aileen Balkow |
title |
A novel crosstalk between Alk7 and cGMP signaling differentially regulates brown adipocyte function |
title_short |
A novel crosstalk between Alk7 and cGMP signaling differentially regulates brown adipocyte function |
title_full |
A novel crosstalk between Alk7 and cGMP signaling differentially regulates brown adipocyte function |
title_fullStr |
A novel crosstalk between Alk7 and cGMP signaling differentially regulates brown adipocyte function |
title_full_unstemmed |
A novel crosstalk between Alk7 and cGMP signaling differentially regulates brown adipocyte function |
title_sort |
novel crosstalk between alk7 and cgmp signaling differentially regulates brown adipocyte function |
publisher |
Elsevier |
series |
Molecular Metabolism |
issn |
2212-8778 |
publishDate |
2015-08-01 |
description |
Objective: Obesity is an enormous burden for patients and health systems world-wide. Brown adipose tissue dissipates energy in response to cold and has been shown to be metabolically active in human adults. The type I transforming growth factor β (TGFβ) receptor Activin receptor-like kinase 7 (Alk7) is highly expressed in adipose tissues and is down-regulated in obese patients. Here, we studied the function of Alk7 in brown adipocytes.
Methods: Using pharmacological and genetic tools, Alk7 signaling pathway and its effects were studied in murine brown adipocytes. Brown adipocyte differentiation and activation was analyzed.
Results: Alk7 is highly upregulated during differentiation of brown adipocytes. Interestingly, Alk7 expression is increased by cGMP/protein kinase G (PKG) signaling, which enhances brown adipocyte differentiation. Activin AB effectively activates Alk7 and SMAD3 signaling. Activation of Alk7 in brown preadipocytes suppresses the master adipogenic transcription factor PPARγ and differentiation. Stimulation of Alk7 during late differentiation of brown adipocytes reduces lipid content and adipogenic marker expression but enhances UCP1 expression.
Conclusions: We found a so far unknown crosstalk between cGMP and Alk7 signaling pathways. Tight regulation of Alk7 is required for efficient differentiation of brown adipocytes. Alk7 has differential effects on adipogenic differentiation and the development of the thermogenic program in brown adipocytes. |
topic |
Alk7 cGMP Brown adipocytes UCP1 Activin |
url |
http://www.sciencedirect.com/science/article/pii/S2212877815000976 |
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