TY - JOUR
T1 - Trehalose inhibits solute carrier 2A (SLC2A) proteins to induce autophagy and prevent hepatic steatosis
AU - DeBosch, Brian J.
AU - Heitmeier, Monique R.
AU - Mayer, Allyson L.
AU - Higgins, Cassandra B.
AU - Crowley, Jan R.
AU - Kraft, Thomas E.
AU - Chi, Maggie
AU - Newberry, Elizabeth P.
AU - Chen, Zhouji
AU - Finck, Brian N.
AU - Davidson, Nicholas O.
AU - Yarasheski, Kevin E.
AU - Hruz, Paul W.
AU - Moley, Kelle H.
N1 - Funding Information:
We thank H. Virgin, Washington University School of Medicine, for the ATG16L1HM mouse line. Funding: B.J.D. is a scholar of the Washington University Child Health Research Center (K12HD076224) and of the Children''s Discovery Institute (MI-FR-2014-426). This work was also supported by grants from Robert Wood Johnson Foundation, the AGA (American Gastroenterological Association)–Gilead Sciences Research Scholar Award in Liver Disease, the Pediatric Scientist Development Program (K12HD000850-29), the Nutrition Obesity Research Center (P30DK056341), the Washington University Digestive Disease Research Core Center (P30DK52574 to B.J.D. and N.O.D., specifically the Administration and Resource Access Core, the Advanced Imaging and Tissue Analysis Core, and the Murine Models Core; HL-38180 and DK-56260 to N.O.D.; and R01-DK078187 to B.N.F.), American Heart Association (grant 14PRE18320006 to T.E.K.), the Washington University S. T. Olin Fellowship (A.L.M.), the Washington University NIGMS (National Institute of General Medical Sciences) Institutional Training Grant in Cell and Molecular Biosciences (T32GM007067 to A.L.M.), NSF Graduate Student Fellowship (DGE-1143954), and the Washington University Biomedical Mass Spectrometry Research Facility (P41 GM103422, P30 DK020579). Author contributions:B.J.D., M.R.H., C.B.H., A.L.M., Z.C., M.C., T.E.K., E.P.N., B.N.F., N.O.D., K.E.Y., P.W.H., and K.H.M. designed the experiments. B.J.D., M.R.H., C.B.H., A.L.M., J.R.C., M.C., Z.C., E.P.N., and T.E.K. performed the experiments. B.J.D., M.H., C.B.H., A.L.M., Z.C., M.C., T.E.K., E.P.N., B.N.F., K.E.Y., P.W.H., and K.H.M. analyzed the data. B.J.D. wrote the manuscript. B.J.D., M.R.H., C.B.H., A.L.M., Z.C., T.E.K., B.N.F., N.O.D., K.E.Y., P.W.H., and K.H.M. edited and revised the manuscript. Competing interests: K.H.M. is on the scientific board of advisors for OvaScience. Data and materials availability: There are no restrictions on materials used in this study. Data and materials availability: There are no restrictions on materials used in this study.
Publisher Copyright:
© 2016 by the American Association for the Advancement of Science.
PY - 2016/2/23
Y1 - 2016/2/23
N2 - 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 inhibitedmembers of the SLC2A (also known asGLUT) 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 primarymurine hepatocyte cultures. Our data indicated that trehalose triggers beneficial cellular autophagy by inhibiting glucose transport.
AB - 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 inhibitedmembers of the SLC2A (also known asGLUT) 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 primarymurine hepatocyte cultures. Our data indicated that trehalose triggers beneficial cellular autophagy by inhibiting glucose transport.
UR - http://www.scopus.com/inward/record.url?scp=84959345504&partnerID=8YFLogxK
U2 - 10.1126/scisignal.aac5472
DO - 10.1126/scisignal.aac5472
M3 - Article
C2 - 26905426
AN - SCOPUS:84959345504
SN - 1945-0877
VL - 9
JO - Science Signaling
JF - Science Signaling
IS - 416
M1 - RA21
ER -