Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.02.363440v1?rss=1 Authors: Wieser, B. I., Pena de la Sancha, P., Schauer, S., Reicher, H., Sattler, W., Breinbauer, R., Schweiger, M., Espenshade, P. J., Zechner, R., Hoefler, G., Vesely, P. W. Abstract: 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 hyperactivated 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. Copy rights belong to original authors. Visit the link for more info