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High fat feeding impairs select features of M1 polarization in CD11c+ adipose tissue macrophages
Author(s) -
Bennett Grace,
Shaul Merav E.,
Strissel Katherine J.,
Defuria Jason,
Greenberg Andrew S.,
Obin Martin S.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.724.3
Subject(s) - adipose tissue , cd11c , medicine , endocrinology , cd163 , tlr2 , inflammation , tlr4 , chemistry , white adipose tissue , downregulation and upregulation , nitric oxide synthase , biology , nitric oxide , macrophage , biochemistry , in vitro , gene , phenotype
Toll‐Like Receptor (TLR) activation by saturated fatty acids and endotoxin is proposed to polarize recruited CD11c expressing adipose tissue macrophages (ATMΦ) toward the pro‐inflammatory (M1) state. This activation exacerbates adipose tissue (AT) inflammation as well as the metabolic and cardiovascular complications of obesity. Our objective was to assess M1/M2 activation of ATMΦ in high fat‐fed (obese) mice. Methods Gene expression (GE) of TLR2/4 and the M1 hallmark, inducible nitric oxide synthase (iNOS) was measured by QPCR in ATMΦs isolated by FACS from perigonadal AT of male C57BL/6j mice fed either a high fat diet (HFD, 60%/54% total energy from fat/lard) or low fat diet (LFD, 10%/4% energy from fat/lard) for 8 or 12 weeks. Results M1 markers (IL‐1β, IL‐12) were upregulated and M2 markers (CD206, CD163, IL‐10) were downregulated in CD11c+ ATMΦs from HFD mice, indicating M1 polarization. Surprisingly, TLR4 GE was reduced by 50% in CD11c+ ATMΦs at weeks 8 and 12 (p<0.05), and TLR2 GE was reduced 2–3 fold at week 12 (p= 0.001). iNOS GE was reduced >5‐fold at weeks 8 and 12 (p≤0.01). These data suggest that chronic HFD selectively impairs important aspects of innate immunity. How and where (bone marrow? circulation?) these effects of HFD on ATMΦs are initially manifest, their impact on metabolism and the role of specific fatty acids in this process remain to be elucidated. Grant Funding Source : NIH DK074979 , NIH T32 HL069772‐07 , Takeda Pharmaceuticals and USDA‐ARS # 5819507707