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Sci. Signal., 1 December 2009
Vol. 2, Issue 99, p. ra78
[DOI: 10.1126/scisignal.2000511]

RESEARCH ARTICLES

Protein Kinase G Controls Brown Fat Cell Differentiation and Mitochondrial Biogenesis

Bodo Haas1, Peter Mayer2*, Katja Jennissen1*, Daniela Scholz1, Mauricio Berriel Diaz3, Wilhelm Bloch4, Stephan Herzig3, Reinhard Fässler5, and Alexander Pfeifer1,6{dagger}

1 Institute for Pharmacology and Toxicology, Biomedical Center, University of Bonn, 53105 Bonn, Germany.
2 Federal Institute for Drugs and Medical Devices, 53175 Bonn, Germany.
3 Molecular Metabolic Control, DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ) Heidelberg, 69120 Heidelberg, Germany.
4 Department of Molecular and Cellular Sport Medicine, German Sport University, 50933 Cologne, Germany.
5 Department of Molecular Medicine, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
6 Pharma-Center, University of Bonn, 53105 Bonn, Germany.

* These authors contributed equally to this work.

Abstract: Brown adipose tissue (BAT) is a primary site of energy expenditure through thermogenesis, which is mediated by the uncoupling protein–1 (UCP-1) in mitochondria. Here, we show that protein kinase G (PKG) is essential for brown fat cell differentiation. Induction of adipogenic markers and fat storage was impaired in the absence of PKGI. Furthermore, PKGI mediated the ability of nitric oxide (NO) and guanosine 3',5'-monophosphate (cGMP) to induce mitochondrial biogenesis and increase the abundance of UCP-1. Mechanistically, we found that PKGI controlled insulin signaling in BAT by inhibiting the activity of RhoA and Rho-associated kinase (ROCK), thereby relieving the inhibitory effects of ROCK on insulin receptor substrate–1 and activating the downstream phosphoinositide 3-kinase–Akt cascade. Thus, PKGI links NO and cGMP signaling with the RhoA-ROCK and the insulin pathways, thereby controlling induction of adipogenic and thermogenic programs during brown fat cell differentiation.

{dagger} To whom correspondence should be addressed. E-mail: alexander.pfeifer{at}uni-bonn.de

Citation: B. Haas, P. Mayer, K. Jennissen, D. Scholz, M. B. Diaz, W. Bloch, S. Herzig, R. Fässler, A. Pfeifer, Protein Kinase G Controls Brown Fat Cell Differentiation and Mitochondrial Biogenesis. Sci. Signal. 2, ra78 (2009).

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