@article{10902/37223,
year = {2024},
url = {https://hdl.handle.net/10902/37223},
abstract = {Promoting brown adipose tissue (BAT) activity innovatively targets obesity and metabolic disease. While thermogenic activation of BAT is well understood, the rheostatic regulation of BAT to avoid excessive energy dissipation remains ill-defined. Here, we demonstrate that adenylyl cyclase 3 (AC3) is key for BAT function. We identified a cold-inducible promoter that generates a 5' truncated AC3 mRNA isoform (Adcy3-at), whose expression is driven by a cold-induced, truncated isoform of PPARGC1A (PPARGC1A-AT). Male mice lacking Adcy3-at display increased energy expenditure and are resistant to obesity and ensuing metabolic imbalances. Mouse and human AC3-AT are retained in the endoplasmic reticulum, unable to translocate to the plasma membrane and lack enzymatic activity. AC3-AT interacts with AC3 and sequesters it in the endoplasmic reticulum, reducing the pool of adenylyl cyclases available for G-protein-mediated cAMP synthesis. Thus, AC3-AT acts as a cold-induced rheostat in BAT, limiting adverse consequences of cAMP activity during chronic BAT activation.},
publisher = {Nature Research},
publisher = {Nature Metabolism, 2024, 6, 1053-1075},
title = {Cold-induced expression of a truncated adenylyl cyclase 3 acts as rheostat to brown fat function},
author = {Khani, Sajjad and Topel, Hande and Kardinal, Ronja and Tavanez, Ana Rita and Josephrajan, Ajeetha and Larsen, Bjiork Ditlev Marcher and Gaudry, Michael James and Leyendecker, Philipp and Egedal, Nadia Miencke and Güller, Aylin Seren and Stanic, Natasa and Ruppert, Phillip M. M. and Gaziano, Isabella and Hansmeier, Nils Rouven and Schmidt, Elena and Klemm, Paul and Vagliano, Lara-Marie and Stahl, Rainer and Rada Iglesias, Álvaro},
}