title: Trehalose inhibits solute carrier 2A (SLC2A) proteins to induce autophagy and prevent hepatic steatosis.
abstract: Trehalose is a naturally occurring disaccharide that has gained attention for its ability to induce cellular autophagy and mitigate diseases related to pathological protein aggregation. Despite decades of ubiquitous use as a nutraceutical, preservative, and humectant, its mechanism of action remains elusive. We showed that trehalose inhibited members of the SLC2A (also known as GLUT) family of glucose transporters. Trehalose-mediated inhibition of glucose transport induced AMPK (adenosine 5'-monophosphate-activated protein kinase)-dependent autophagy and regression of hepatic steatosis in vivo and a reduction in the accumulation of lipid droplets in primary murine hepatocyte cultures. Our data indicated that trehalose triggers beneficial cellular autophagy by inhibiting glucose transport.
authors.affiliation: Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USA. debosch_b@kids.wustl.edu.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: DeBosch
authors.affiliation: Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Monique R
authors.initials: MR
authors.lastname: Heitmeier
authors.affiliation: Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Allyson L
authors.initials: AL
authors.lastname: Mayer
authors.affiliation: Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Cassandra B
authors.initials: CB
authors.lastname: Higgins
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Jan R
authors.initials: JR
authors.lastname: Crowley
authors.affiliation: Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Kraft
authors.affiliation: Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Maggie
authors.initials: M
authors.lastname: Chi
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Elizabeth P
authors.initials: EP
authors.lastname: Newberry
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Zhouji
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Brian N
authors.initials: BN
authors.lastname: Finck
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Nicholas O
authors.initials: NO
authors.lastname: Davidson
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Kevin E
authors.initials: KE
authors.lastname: Yarasheski
authors.affiliation: Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Hruz
authors.affiliation: Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Kelle H
authors.initials: KH
authors.lastname: Moley
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001343:Autophagy; D005234:Fatty Liver / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D014199:Trehalose / Q000378:metabolism*
chemical_list: D051246:Glucose Transport Proteins, Facilitative; D014199:Trehalose; D055372:AMP-Activated Protein Kinases