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SCD1 deficiency prevents obesity‐induced macrophage recruitment into white adipose tissue and improves the associated adipose insulin resistance
Author(s) -
Liu Xueqing,
Flowers Matthew,
Miyazaki Makoto,
Chu Kiki,
Ntambi James
Publication year - 2007
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.21.5.a295-b
Subject(s) - white adipose tissue , adipose tissue , proinflammatory cytokine , endocrinology , medicine , insulin resistance , inflammation , adipocyte , adipose tissue macrophages , chemistry , macrophage , biology , diabetes mellitus , biochemistry , in vitro
Macrophage infiltration into adipose tissue is a major cause for chronic inflammation in obesity. This study has explored the role of SCD1 in the recruitment of macrophage into white adipose tissue (WAT) using Agouti mouse model. Compared to Agouti mice, the WAT expression of proinflammatory genes is significantly lower in Agouti:SCD1‐/‐ mice, consistent with the reduced DNA binding activity of NF‐¦ÊB. Further immunohistological staining of WAT section and macrophage marker gene expression show the prevention of macrophage infiltration and formation of multinucleated giant macrophages in Agouti:SCD1‐/‐ mice, indicating that the decreased WAT inflammation is primarily due to reduced macrophage recruitment rather than suppression of proinflammatory genes in resident macrophages. This lower WAT inflammation is seen with improved WAT insulin sensitivity in Agouti:SCD1‐/‐ mice. To elucidate how SCD1 deficiency prevents adipose macrophage infiltration, we found that the adipocyte apoptosis, a major cause for macrophage infiltration, is prevented in WAT of Agouti:SCD1‐/‐ mice. Fatty acid composition analysis of triacylglycerol showed a dramatically higher percentage of saturated fatty acids (16:0 and 18:0) with lower monounsaturated fatty acids (16:1 and 18:1) in WAT of Agouti:SCD1‐/‐ mice. Fatty acid oxidation in WAT of Agouti:SCD1‐/‐ is not higher than that from Agouti mice, but with surprisingly higher expression of key lipogenic enzyme GPAT. We hypothesize that SCD1 deficiency in Agouti obese mice directs WAT to triacylglercerol synthesis rather than fatty acid oxidation, which neutralizes the excess saturated fatty acids, resulting in reduction of adipocyte apoptosis with marked decrease of macrophage infiltration.