Metabolic dysfunction induced by a high‐fat diet modulates hematopoietic stem and myeloid progenitor cells in brown adipose tissue of mice

Kyle T Mincham, Kunjal Panchal, Prue H Hart, Robyn M Lucas, Martin Feelisch, Richard B Weller, Vance B Matthews, Deborah H Strickland, Shelley Gorman

Research output: Contribution to journalArticlepeer-review

Abstract

Brown adipose tissue (BAT) may be an important metabolic regulator of
whole-body glucose. While important roles have been ascribed to macrophages
in regulating metabolic functions in BAT, little is known of the roles of other
immune cells subsets, particularly dendritic cells (DCs). Eating a high-fat diet
may compromise the development of hematopoietic stem and progenitor cells
(HSPCs)—which give rise to DCs—in bone marrow, with less known of its
effects in BAT. We have previously demonstrated that ongoing exposure to
low-dose ultraviolet radiation (UVR) significantly reduced the ‘whitening’ effect
of eating a high-fat diet upon interscapular (i) BAT of mice. Here, we
examined whether this observation may be linked to changes in the phenotype
of HSPCs and myeloid-derived immune cells in iBAT and bone marrow of
mice using 12-colour flow cytometry. Many HSPC subsets declined in both
iBAT and bone marrow with increasing metabolic dysfunction. Conversely,
with rising adiposity and metabolic dysfunction, conventional DCs (cDCs)
increased in both of these tissues. When compared with a low-fat diet,
consumption of a high-fat diet significantly reduced proportions of myeloid,
common myeloid and megakaryocyte–erythrocyte progenitors in iBAT, and
short-term hematopoietic stem cells in bone marrow. In mice fed the high-fat
diet, exposure to low-dose UVR significantly reduced proportions of cDCs in
iBAT, independently of nitric oxide release from irradiated skin [blocked using
the scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-
oxide potassium salt (cPTIO)], but did not significantly modify HSPC subsets
in either tissue. Further studies are needed to determine whether changes in
these cell populations contribute towards metabolic dysfunction.
Original languageEnglish
JournalImmunology and Cell Biology
DOIs
Publication statusPublished - 18 Apr 2021

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