RT Journal Article
SR Electronic
T1 Adipose Triglyceride Lipase is needed for homeostatic control of Sterol Element-Binding Protein-1c driven hepatic lipogenesis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.11.02.363440
DO 10.1101/2020.11.02.363440
A1 Beatrix Irene Wieser
A1 Paola Peña de la Sancha
A1 Silvia Schauer
A1 Helga Reicher
A1 Wolfgang Sattler
A1 Rolf Breinbauer
A1 Martina Schweiger
A1 Peter John Espenshade
A1 Rudolf Zechner
A1 Gerald Hoefler
A1 Paul Willibald Vesely
YR 2020
UL http://biorxiv.org/content/early/2020/11/11/2020.11.02.363440.abstract
AB Sterol Regulatory Element-Binding Protein-1c (SREBP-1c) is translated as an inactive precursor-protein that is proteolytically activated to promote fatty-acid (FA) biosynthesis, when unsaturated (u)FAs are scarce. During fasting, however, lipogenesis is low, and adipose-tissue lipolysis supplies the organism with FAs. Adipose TriGlyceride Lipase (ATGL) is the rate-limiting enzyme for lipolysis, and it preferentially hydrolyzes uFAs. Therefore, we hypothesized that ATGL-derived FAs may suppress the proteolytic activation of SREBP-1c in the liver. Here we show that (i) SREBP-1c is inactive during fasting but active after refeeding, (ii) uFA species liberated by ATGL suppress SREBP-1c activation in vitro, (iii) SREBP-1c is hyper-activated in livers of mice lacking ATGL, and (iv) pharmacological inhibition of ATGL selectively activates SREBP-1c in hepatocytes. Our findings highlight an ATGL/SREBP-1c axis, instrumental to coordinate lipogenesis and lipolysis, whose homeostatic regulation is crucial to avoid severe diseases including diabetes, cardiomyopathy, and even cancer.Competing Interest StatementThe authors have declared no competing interest.