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PGC‐1β suppresses saturated fatty acid‐induced macrophage inflammation by inhibiting TAK1 activation
Author(s) -
Chen Hongen,
Liu Yan,
Li Di,
Song Jiayi,
Xia Min
Publication year - 2016
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1002/iub.1470
Subject(s) - inflammation , coactivator , proinflammatory cytokine , microbiology and biotechnology , macrophage , chemistry , protein kinase b , adipose tissue , peroxisome proliferator activated receptor , kinase , receptor , endocrinology , signal transduction , medicine , biology , biochemistry , transcription factor , immunology , in vitro , gene
Inflammation of infiltrated macrophages in adipose tissue is a key contributor to the initiation of adipose insulin resistance. These macrophages are exposed to high local concentrations of free fatty acids (FFAs) and can be proinflammatory activated by saturated fatty acids (SFAs). However, the regulatory mechanisms on SFA‐induced macrophage inflammation are still elusive. Peroxisome proliferator‐activated receptor γ coactivator‐1β (PGC‐1β) is a member of the PGC‐1 family of transcriptional coactivators and has been reported to play a key role in SFAs metabolism and in the regulation of inflammatory signaling. However, it remains unclear whether PGC‐1β is involved in SFA‐induced macrophage inflammation. In this study, we found that PGC‐1β expression was significantly decreased in response to palmitic acid (PA) in macrophages in a dose dependent manner. PGC‐1β inhibited PA induced TNFα, MCP‐1, and IL‐1β mRNA and protein expressions. Furthermore, PGC‐1β significantly antagonized PA induced macrophage nuclear factor‐κB (NF‐κB) p65 and JUN N‐terminal kinase activation. Mechanistically, we revealed that TGF‐β‐activated kinase 1 (TAK1) and its adaptor protein TAK1 binding protein 1 (TAB1) played a dominant role in the regulatory effects of PGC‐1β. We confirmed that PGC‐1β inhibited downstream inflammatory signals via binding with TAB1 and thus preventing TAB1/TAK1 binding and TAK1 activation. Finally, we showed that PGC‐1β overexpression in PA treated macrophages improved adipocytes PI3K‐Akt insulin signaling in a paracrine fashion. Collectively, our results uncovered a novel mechanism on how macrophage inflammation induced by SFAs was regulated and suggest a potential target in the treatment of obesity induced insulin resistance. © 2016 IUBMB Life, 68(2):145–155, 2016