Protein kinase G controls brown fat cell differentiation and mitochondrial biogenesis.
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.
Haas
Bodo
B
Institute for Pharmacology and Toxicology, Biomedical Center, University of Bonn, Bonn, Germany.
Mayer
Peter
P
Jennissen
Katja
K
Scholz
Daniela
D
Berriel Diaz
Mauricio
M
Bloch
Wilhelm
W
Herzig
Stephan
S
Fässler
Reinhard
R
Pfeifer
Alexander
A
D050156:Adipogenesis; D002001:Adipose Tissue, Brown / Q000166:cytology*; D000818:Animals; D002454:Cell Differentiation; D006152:Cyclic GMP; D017869:Cyclic GMP-Dependent Protein Kinases / Q000172:deficiency / Q000502:physiology*; D007328:Insulin / Q000378:metabolism; D007473:Ion Channels; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins; D009569:Nitric Oxide; D000071256:Uncoupling Protein 1; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein
D007328:Insulin; D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D009569:Nitric Oxide; D054460:rho-Associated Kinases; D017869:Cyclic GMP-Dependent Protein Kinases; D020742:rhoA GTP-Binding Protein; D006152:Cyclic GMP