title: Macrophage Proliferation Sustains Adipose Tissue Inflammation in Formerly Obese Mice.
abstract: Obesity causes dramatic proinflammatory changes in the adipose tissue immune environment, but relatively little is known regarding how this inflammation responds to weight loss (WL). To understand the mechanisms by which meta-inflammation resolves during WL, we examined adipose tissue leukocytes in mice after withdrawal of a high-fat diet. After 8 weeks of WL, mice achieved similar weights and glucose tolerance values as age-matched lean controls but showed abnormal insulin tolerance. Despite fat mass normalization, total and CD11c+adipose tissue macrophage (ATM) content remained elevated in WL mice for up to 6 months and was associated with persistent fibrosis in adipose tissue. ATMs in formerly obese mice demonstrated a proinflammatory profile, including elevated expression of interferon-γ, tumor necrosis factor-α, and interleukin-1β. T-cell-deficient Rag1-/-mice showed a degree of ATM persistence similar to that in WT mice, but with reduced inflammatory gene expression. ATM proliferation was identified as the predominant mechanism by which ATMs are retained in adipose tissue with WL. Our study suggests that WL does not completely resolve obesity-induced ATM activation, which may contribute to the persistent adipose tissue damage and reduced insulin sensitivity observed in formerly obese mice.
authors.affiliation: Graduate Program in Immunology, University of Michigan Medical School, Ann Arbor, MI.
authors.forename: Brian F
authors.identifier: 0000-0001-6549-4230
authors.initials: BF
authors.lastname: Zamarron
authors.affiliation: College of Literature Sciences and Arts, University of Michigan, Ann Arbor, MI.
authors.forename: Taleen A
authors.initials: TA
authors.lastname: Mergian
authors.affiliation: Soonchunhyang Institute of Medi-bio Science, Soonchunhyang University, Cheonan-si, Chungcheongnam-do, Korea.
authors.forename: Kae Won
authors.initials: KW
authors.lastname: Cho
authors.affiliation: Department of Cellular and Molecular Biology, University of Michigan Medical School, Ann Arbor, MI.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Martinez-Santibanez
authors.affiliation: College of Literature Sciences and Arts, University of Michigan, Ann Arbor, MI.
authors.forename: Danny
authors.initials: D
authors.lastname: Luan
authors.affiliation: Graduate Program in Immunology, University of Michigan Medical School, Ann Arbor, MI.|Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, MI.
authors.forename: Kanakadurga
authors.identifier: 0000-0001-8728-3800
authors.initials: K
authors.lastname: Singer
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, MI.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: DelProposto
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, MI.
authors.forename: Lynn M
authors.initials: LM
authors.lastname: Geletka
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, MI.
authors.forename: Lindsey A
authors.identifier: 0000-0002-1756-0325
authors.initials: LA
authors.lastname: Muir
authors.affiliation: Graduate Program in Immunology, University of Michigan Medical School, Ann Arbor, MI clumeng@umich.edu.|Department of Cellular and Molecular Biology, University of Michigan Medical School, Ann Arbor, MI.|Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, MI.
authors.forename: Carey N
authors.identifier: 0000-0003-0303-2604
authors.initials: CN
authors.lastname: Lumeng
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000276:immunology*; D000818:Animals; D001835:Body Weight; D049109:Cell Proliferation; D059305:Diet, High-Fat; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D005951:Glucose Tolerance Test; D018398:Homeodomain Proteins / Q000235:genetics; D015151:Immunoblotting; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology; D007328:Insulin / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008820:Mice, Obese; D009765:Obesity / Q000276:immunology*; D013601:T-Lymphocytes; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D015431:Weight Loss / Q000276:immunology*
chemical_list: D018398:Homeodomain Proteins; C587672:IL1B protein, mouse; D007328:Insulin; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; C064658:RAG-1 protein; D007371:Interferon-gamma