We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Myeloid-specific Asxl2 deletion limits diet-induced obesity by regulating energy expenditure.
- Authors
Wei Zou; Rohatgi, Nidhi; Brestoff, Jonathan R.; Moley, John R.; Yongjia Li; Williams, Jesse W.; Alippe, Yael; Hua Pan; Pietka, Terri A.; Mbalaviele, Gabriel; Newberry, Elizabeth P.; Davidson, Nicholas O.; Dey, Anwesha; Shoghi, Kooresh I.; Head, Richard D.; Wickline, Samuel A.; Randolph, Gwendalyn J.; Abumrad, Nada A.; Teitelbaum, Steven L.; Zou, Wei
- Abstract
We previously established that global deletion of the enhancer of trithorax and polycomb (ETP) gene, Asxl2, prevents weight gain. Because proinflammatory macrophages recruited to adipose tissue are central to the metabolic complications of obesity, we explored the role of ASXL2 in myeloid lineage cells. Unexpectedly, mice without Asxl2 only in myeloid cells (Asxl2ΔLysM) were completely resistant to diet-induced weight gain and metabolically normal despite increased food intake, comparable activity, and equivalent fecal fat. Asxl2ΔLysM mice resisted HFD-induced adipose tissue macrophage infiltration and inflammatory cytokine gene expression. Energy expenditure and brown adipose tissue metabolism in Asxl2ΔLysM mice were protected from the suppressive effects of HFD, a phenomenon associated with relatively increased catecholamines likely due to their suppressed degradation by macrophages. White adipose tissue of HFD-fed Asxl2ΔLysM mice also exhibited none of the pathological remodeling extant in their control counterparts. Suppression of macrophage Asxl2 expression, via nanoparticle-based siRNA delivery, prevented HFD-induced obesity. Thus, ASXL2 controlled the response of macrophages to dietary factors to regulate metabolic homeostasis, suggesting modulation of the cells' inflammatory phenotype may impact obesity and its complications.
- Subjects
CELL metabolism; PREVENTION of obesity; PROTEIN metabolism; ENERGY metabolism; PROTEINS; OBESITY; RESEARCH; ANIMAL experimentation; INFLAMMATION; RESEARCH methodology; MACROPHAGES; ANIMAL nutrition; RNA; EVALUATION research; MEDICAL cooperation; WEIGHT gain; COMPARATIVE studies; CELLS; IMMUNITY; RESEARCH funding; GENETIC techniques; MICE; ADIPOSE tissues
- Publication
Journal of Clinical Investigation, 2020, Vol 130, Issue 5, p2644
- ISSN
0021-9738
- Publication type
journal article
- DOI
10.1172/JCI128687