title: Transforming growth factor β/activin signaling functions as a sugar-sensing feedback loop to regulate digestive enzyme expression.
abstract: Organisms need to assess their nutritional state and adapt their digestive capacity to the demands for various nutrients. Modulation of digestive enzyme production represents a rational step to regulate nutriment uptake. However, the role of digestion in nutrient homeostasis has been largely neglected. In this study, we analyzed the mechanism underlying glucose repression of digestive enzymes in the adult Drosophila midgut. We demonstrate that glucose represses the expression of many carbohydrases and lipases. Our data reveal that the consumption of nutritious sugars stimulates the secretion of the transforming growth factor β (TGF-β) ligand, Dawdle, from the fat body. Dawdle then acts via circulation to activate TGF-β/Activin signaling in the midgut, culminating in the repression of digestive enzymes that are highly expressed during starvation. Thus, our study not only identifies a mechanism that couples sugar sensing with digestive enzyme expression but points to an important role of TGF-β/Activin signaling in sugar metabolism.
authors.affiliation: Global Health Institute, School of Life Sciences, EPFL, Station 19, 1015 Lausanne, Switzerland. Electronic address: alfred.chng@epfl.ch.
authors.forename: Wen-Bin Alfred
authors.initials: WA
authors.lastname: Chng
authors.affiliation: Global Health Institute, School of Life Sciences, EPFL, Station 19, 1015 Lausanne, Switzerland.
authors.forename: Maroun S Bou
authors.initials: MSB
authors.lastname: Sleiman
authors.affiliation: Global Health Institute, School of Life Sciences, EPFL, Station 19, 1015 Lausanne, Switzerland.
authors.forename: Fanny
authors.initials: F
authors.lastname: Schüpfer
authors.affiliation: Global Health Institute, School of Life Sciences, EPFL, Station 19, 1015 Lausanne, Switzerland. Electronic address: bruno.lemaitre@epfl.ch.
authors.forename: Bruno
authors.initials: B
authors.lastname: Lemaitre
mesh_terms: D028341:Activins / Q000378:metabolism*; D000818:Animals; D004330:Drosophila; D005947:Glucose / Q000378:metabolism; D006026:Glycoside Hydrolases / Q000096:biosynthesis* / Q000378:metabolism; D008071:Lipoprotein Lipase / Q000096:biosynthesis* / Q000378:metabolism; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D016212:Transforming Growth Factor beta; D028341:Activins; D008071:Lipoprotein Lipase; D006026:Glycoside Hydrolases; C019822:carbohydrase; D005947:Glucose