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Long, F.* ; Ghosh, A.* ; Xu, T.* ; Ding, L.* ; Wu, C.* ; Khandelwal, R.* ; Noé, F.* ; Sun, W.* ; Dong, H.* ; Wang, T.* ; Hoffmann, A. ; Gardeux, V.* ; Deplancke, B.* ; Abu-Nawwas, L.* ; Stefanicka, P.* ; Varga, L.* ; Ruiz, J.R.* ; Blüher, M. ; Balaz, M.* ; Sharma, A.K.* ; Wolfrum, C.*

MEDAG functions as an A-kinase-anchoring protein in adipocytes.

Mol. Cell 86, 937-953.e9 (2026)
Verlagsversion Forschungsdaten DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
Induction of catabolic adipocyte activity independent of mitochondrial uncoupling to induce energy expenditure has received increasing attention. In this study, we identified mesenteric estrogen-dependent adipogenesis gene (MEDAG), a poorly studied gene, as a promising therapeutic target for enhancing energy expenditure in adipocytes. We demonstrated that adipose MEDAG expression positively correlates with obesity and metabolic dysfunction in humans. Consistently, adipocyte-specific ablation of Medag in mice leads to increased energy expenditure, offering protection from diet-induced obesity. Mechanistically, we show that MEDAG functions as an A-kinase-anchoring protein (AKAP), which can directly regulate protein kinase A (PKA) activity through a negative feedback loop, involving direct interaction with PKA leading to MEDAG phosphorylation and consequent feedback fine-tuning of PKA activity. Specifically, the direct interaction of MEDAG with the PKA-RIIβ subunit regulates the stability of PKA-RIIβ to prevent PKA hyperactivation. These findings position MEDAG as a target for adipose energy expenditure and uncover its AKAP activity.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Akap ; Medag ; Pka ; Camp-pka Signaling ; Catabolic Adipocytes ; Energy Expenditure ; Glucose Uptake And Utilization ; Lipolysis ; Metabolic Diseases ; Obesity; Brown Adipose-tissue; Ppar-gamma; Fat; Identification; Metabolism; Signal; Mouse; Gene; Camp; Disruption
ISSN (print) / ISBN 1097-2765
e-ISSN 1097-4164
Zeitschrift Molecular Cell
Quellenangaben Band: 86, Heft: 5, Seiten: 937-953.e9 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Begutachtungsstatus Peer reviewed
Institut(e) Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)
Förderungen
r Diabetesforschung (DZD)
Deutsches Zentrum fuuml
DFG Projektnummer
VEGA