HDL and Glut1 inhibition reverse a hypermetabolic state in mouse models of myeloproliferative disorders

Emmanuel L. Gautier, Marit Westerterp, Neha Bhagwat, Serge Cremers, Alan Shih, Omar Abdel-Wahab, Dieter Lütjohann, Gwendalyn J. Randolph, Ross L. Levine, Alan R. Tall, Laurent Yvan-Charvet

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


A high metabolic rate in myeloproliferative disorders is a common complication of neoplasms, but the underlying mechanisms are incompletely understood. Using three different mouse models of myeloproliferative disorders, including mice with defective cholesterol efflux pathways and two models based on expression of human leukemia disease alleles, we uncovered a mechanism by which proliferating and inflammatory myeloid cells take up and oxidize glucose during the feeding period, contributing to energy dissipation and subsequent loss of adipose mass. In vivo, lentiviral inhibition of Glut1 by shRNA prevented myeloproliferation and adipose tissue loss in mice with defective cholesterol efflux pathway in leukocytes. Thus, Glut1 was necessary to sustain proliferation and potentially divert glucose from fat storage. We also showed that overexpression of the human ApoA-I transgene to raise high-density lipoprotein (HDL) levels decreased Glut1 expression, dampened myeloproliferation, and prevented fat loss. These experiments suggest that inhibition of Glut-1 and HDL cholesterol-raising therapies could provide novel therapeutic approaches to treat the energy imbalance observed in myeloproliferative disorders.

Original languageEnglish
Pages (from-to)339-353
Number of pages15
JournalJournal of Experimental Medicine
Issue number2
StatePublished - Feb 2013


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