Involvement of a cGMP-dependent pathway in the natriuretic peptide-mediated hormone-sensitive lipase phosphorylation in human adipocytes.
Our previous studies have demonstrated that natriuretic peptides (NPs), peptide hormones with natriuretic, diuretic, and vasodilating properties, exert a potent control on the lipolysis in human adipocytes via the activation of the type A guanylyl cyclase receptor (1, 2). In the current study we investigated the intracellular mechanisms involved in the NP-stimulated lipolytic effect in human preadipocytes and adipocytes. We demonstrate that the atrial NP (ANP)-induced lipolysis in human adipocytes was associated with an enhanced serine phosphorylation of the hormone-sensitive lipase (HSL). Both ANP-mediated lipolysis and HSL phosphorylation were inhibited in the presence of increasing concentrations of the guanylyl cyclase inhibitor LY-83583. ANP did not modulate the activity of the cAMP-dependent protein kinase (PKA). Moreover, H-89, a PKA inhibitor, did not affect the ANP-induced lipolysis. On primary cultures of human preadipocytes, the ANP-mediated lipolytic effect was dependent on the differentiation process. On differentiated human preadipocytes, ANP-mediated lipolysis, associated with an increased phosphorylation of HSL and of perilipin A, was strongly decreased by treatment with the inhibitor of the cGMP-dependent protein kinase I (cGKI), Rp-8-pCPT-cGMPS. Thus, ANP-induced lipolysis in human adipocytes is a cGMP-dependent pathway that induces the phosphorylation of HSL and perilipin A via the activation of cGKI. The present study shows that lipolysis in human adipocytes can be controlled by an independent cGKI-mediated signaling as well as by the classical cAMP/PKA pathway.
Sengenes
Coralie
C
Obesity Research Unit, INSERM U 586, Institut Louis Bugnard, Centre Hospitalier Universitaire Rangueil, Université Paul Sabatier, Toulouse, France. corasengenes@yahoo.com
Bouloumie
Anne
A
Hauner
Hans
H
Berlan
Michel
M
Busse
Rudi
R
Lafontan
Max
M
Galitzky
Jean
J
D017667:Adipocytes / Q000166:cytology / Q000201:enzymology*; D000634:Aminoquinolines / Q000494:pharmacology; D001483:Base Sequence; D002454:Cell Differentiation; D006152:Cyclic GMP / Q000502:physiology*; D017931:DNA Primers; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D045283:Natriuretic Agents / Q000502:physiology*; D010766:Phosphorylation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D002787:Sterol Esterase / Q000378:metabolism*
D000634:Aminoquinolines; D017931:DNA Primers; D004791:Enzyme Inhibitors; D045283:Natriuretic Agents; C041715:6-anilino-5,8-quinolinedione; D020928:Mitogen-Activated Protein Kinases; D002787:Sterol Esterase; D006152:Cyclic GMP