[HTML][HTML] miR-150 regulates obesity-associated insulin resistance by controlling B cell functions

W Ying, A Tseng, RCA Chang, H Wang, Y Lin… - Scientific reports, 2016 - nature.com
W Ying, A Tseng, RCA Chang, H Wang, Y Lin, S Kanameni, T Brehm, A Morin, B Jones…
Scientific reports, 2016nature.com
Adipose tissue resident B cells account for more than 20% of stromal cells within visceral
adipose tissues; however, their functions in the adipose tissue niche are poorly elucidated.
Here we report that miR-150 modulates adipose tissue function by controlling activation of B
cells and their interactions with other immune cells. miR-150KO mice displayed exacerbated
obesity-associated tissue inflammation and systemic insulin resistance, which is
recapitulated by adoptive transfer of B cells, but not purified immunoglobulin, into obese …
Abstract
Adipose tissue resident B cells account for more than 20% of stromal cells within visceral adipose tissues; however, their functions in the adipose tissue niche are poorly elucidated. Here we report that miR-150 modulates adipose tissue function by controlling activation of B cells and their interactions with other immune cells. miR-150KO mice displayed exacerbated obesity-associated tissue inflammation and systemic insulin resistance, which is recapitulated by adoptive transfer of B cells, but not purified immunoglobulin, into obese Bnull mice. Using purified cell populations, we found that enhanced proinflammatory activation of adipose tissue T cells and macrophages was due to miR-150KO B cells action but not cell-autologous mechanisms. miR-150KO B cells displayed significantly enhanced antigen presentation upon stimulation, ultimately leading to elevated inflammation and insulin resistance, compared to wild type B cells. Knockdown of identified miR-150 target genes, Elk1, Etf1 or Myb attenuated B cell action by altering B cell receptor pathways and MHCII cell surface presentation. Our results demonstrate a critical role for miR-150 in regulating B cell functions in adipose tissue which ultimately regulate both metabolic and immunologic homeostasis in the adipose tissue niche.
nature.com