2026-08-29T10:10:16Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/175422024-11-29T19:13:29Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc 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 author 2010-01-20 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. 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 PKA phosphorylates and inactivates AMPKalpha to promote efficient lipolysis.