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Temporal effects of peroxisome proliferator‐activated receptor γ activation on macrophage inflammatory responses (1037.3)
Author(s) -
Guo Xin,
Guo Ting,
Li Honggui,
Pei Ya,
Xu Hang,
Qi Ting,
Hu Xiang,
Zhao Yan,
Zhao Jiajia,
Wu Chaodong
Publication year - 2014
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.28.1_supplement.1037.3
Subject(s) - endocrinology , peroxisome proliferator activated receptor , medicine , macrophage , proinflammatory cytokine , overnutrition , inflammation , pioglitazone , receptor , chemistry , biology , type 2 diabetes , diabetes mellitus , biochemistry , in vitro , obesity
Peroxisome proliferator‐activated receptor γ (PPARγ) activation suppresses macrophage inflammatory responses, thereby improving overnutrition‐associated insulin resistance. Because circadian clocks gate the rhythmicity of macrophage inflammatory responses, we explored the temporal effects of PPARγ activation on macrophage proinflammatory responses. To characterize the rhythmicity of macrophage inflammatory responses, RAW cells were synchronized at CT0 (circadian time 0) and treated with palmitate (250 µM) at 1 hr (CT1), 7 hr (CT7), 13 hr (CT13), and/or 19 hr (CT19) after CT0 for 4 hr. As indicated by the phosphorylation of c‐Jun N‐terminal kinase 1 (JNK1), RAW cells displayed the strongest inflammatory responses at CT7. Although decreased at CT13, JNK phosphorylation remained at relatively high levels at CT13 and CT19. Next, bone marrow‐derived macrophages (BMDM), at CT7 and CT19, were treated with pioglitazone (1 µM) for 48 hr in the presence of lipopolysaccharide for the last 30 min. Consistently, BMBM displayed stronger inflammatory responses at CT7 than at CT19. Interestingly, BMDM also responded better to pioglitazone at CT7 than at CT19. Together, these results suggest that circadian clocks critically regulate the anti‐inflammatory effects of PPARγ activation. As such, time‐based treatment may be an essential strategy for managing overnutrition‐associated metabolic diseases. Grant Funding Source : Supported by ADA, AHA, NIH