title: miR-150 regulates obesity-associated insulin resistance by controlling B cell functions.
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 B(null) 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.
authors.affiliation: Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ying
authors.affiliation: College of Medicine, Texas A&M Health Science Center, College Station, TX, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Tseng
authors.affiliation: Department of Veterinary Physiology &Pharmacology, College of Veterinary Medicine &Biomedical Sciences, Texas A&M University, College Station, TX, USA.
authors.forename: Richard Cheng-An
authors.initials: RC
authors.lastname: Chang
authors.affiliation: Department of Veterinary Physiology &Pharmacology, College of Veterinary Medicine &Biomedical Sciences, Texas A&M University, College Station, TX, USA.
authors.forename: Haiqing
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Veterinary Physiology &Pharmacology, College of Veterinary Medicine &Biomedical Sciences, Texas A&M University, College Station, TX, USA.
authors.forename: Yu-Lieh
authors.initials: YL
authors.lastname: Lin
authors.affiliation: Department of Veterinary Physiology &Pharmacology, College of Veterinary Medicine &Biomedical Sciences, Texas A&M University, College Station, TX, USA.
authors.forename: Srikanth
authors.initials: S
authors.lastname: Kanameni
authors.affiliation: Department of Chemical Engineering, Texas A&M University, College Station, TX, USA.
authors.forename: Tyler
authors.initials: T
authors.lastname: Brehm
authors.affiliation: Department of Veterinary Physiology &Pharmacology, College of Veterinary Medicine &Biomedical Sciences, Texas A&M University, College Station, TX, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Morin
authors.affiliation: Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Jones
authors.affiliation: Department of Agriculture and Life Sciences, Texas A&M University, College Station, TX, USA.
authors.forename: Taylor
authors.initials: T
authors.lastname: Splawn
authors.affiliation: Department of Veterinary Pathobiology, College of Veterinary Medicine &Biomedical Sciences, Texas A&M University, College Station, TX, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Criscitiello
authors.affiliation: College of Medicine, Texas A&M Health Science Center, College Station, TX, USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Golding
authors.affiliation: Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
authors.forename: Fuller W
authors.initials: FW
authors.lastname: Bazer
authors.affiliation: Department of Veterinary Physiology &Pharmacology, College of Veterinary Medicine &Biomedical Sciences, Texas A&M University, College Station, TX, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Safe
authors.affiliation: Department of Immunology, University of Connecticut Health Center, Farmington, CT, USA.
authors.forename: Beiyan
authors.initials: B
authors.lastname: Zhou
mesh_terms: D000273:Adipose Tissue / Q000473:pathology; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D002450:Cell Communication; D005947:Glucose / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000473:pathology; D007333:Insulin Resistance / Q000235:genetics*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D009765:Obesity / Q000235:genetics* / Q000276:immunology*; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D035683:MicroRNAs; C529101:Mirn150 microRNA, mouse; D005947:Glucose
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