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

• DOI: 10.1084/jem.20121357
• Publication Date: 2013-01-15T04:54:00Z
• Authors: Emmanuel L. Gautier; Marit Westerterp; Neha Bhagwat; Serge Cremers; Alan Shih; Omar Abdel-Wahab; Dieter Lütjohann; Gwendalyn J. Rand...; Ross L. Levine; Alan R. Tall; Laurent Yvan-Charvet
• Keywords: Myeloproliferative Disorders

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