Protein Kinase G Controls Brown Fat Cell Differentiation and Mitochondrial Biogenesis
| Autor: | Wilhelm Bloch, Stephan Herzig, Alexander Pfeifer, Mauricio Berriel Diaz, Bodo Haas, Daniela Scholz, Peter Mayer, Katja Jennissen, Reinhard Fässler |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
medicine.medical_specialty
Brown fat cell differentiation Adipose tissue Nitric Oxide Biochemistry Ion Channels Mitochondrial Proteins Mice Adipose Tissue Brown Internal medicine Brown adipose tissue Cyclic GMP-Dependent Protein Kinases medicine Animals Insulin Cyclic GMP Molecular Biology Uncoupling Protein 1 Mice Knockout rho-Associated Kinases Adipogenesis biology Cell Differentiation Cell Biology Thermogenin Mitochondria Insulin receptor medicine.anatomical_structure Endocrinology Mitochondrial biogenesis biology.protein rhoA GTP-Binding Protein cGMP-dependent protein kinase |
| Zdroj: | Science Signaling. 2 |
| ISSN: | 1937-9145 1945-0877 |
| DOI: | 10.1126/scisignal.2000511 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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