2026-08-29T09:25:23Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/175422024-11-29T19:13:29Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Djouder, Nabil
author
Tuerk, Roland D
author
Suter, Marianne
author
Salvioni, Paolo
author
Thali, Ramon F
author
Scholz, Roland
author
Vaahtomeri, Kari
author
Auchli, Yolanda
author
Rechsteiner, Helene
author
Brunisholz, René A
author
Viollet, Benoit
author
Mäkelä, Tomi P
author
Wallimann, Theo
author
Neumann, Dietbert
author
Krek, Wilhelm
funder
Swiss National Science Foundation (SNSF)
funder
European Union (EU)
funder
ETH Zurich
2024-02-08T11:46:29Z
2024-02-08T11:46:29Z
2010-01-20
EMBO J . 2010 ;29(2):469-81.
10.1038/emboj.2009.339
1460-2075
The EMBO journal
19942859
http://hdl.handle.net/20.500.12105/17542
The mobilization of metabolic energy from adipocytes depends on a tightly regulated balance between hydrolysis and resynthesis of triacylglycerides (TAGs). Hydrolysis is stimulated by beta-adrenergic signalling to PKA that mediates phosphorylation of lipolytic enzymes, including hormone-sensitive lipase (HSL). TAG resynthesis is associated with high-energy consumption, which when inordinate, leads to increased AMPK activity that acts to restrain hydrolysis of TAGs by inhibiting PKA-mediated activation of HSL. Here, we report that in primary mouse adipocytes, PKA associates with and phosphorylates AMPKalpha1 at Ser-173 to impede threonine (Thr-172) phosphorylation and thus activation of AMPKalpha1 by LKB1 in response to lipolytic signals. Activation of AMPKalpha1 by LKB1 is also blocked by PKA-mediated phosphorylation of AMPKalpha1 in vitro. Functional analysis of an AMPKalpha1 species carrying a non-phosphorylatable mutation at Ser-173 revealed a critical function of this phosphorylation for efficient release of free fatty acids and glycerol in response to PKA-activating signals. These results suggest a new mechanism of negative regulation of AMPK activity by PKA that is important for converting a lipolytic signal into an effective lipolytic response.
eng
PKA phosphorylates and inactivates AMPKalpha to promote efficient lipolysis.
journal article
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