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Involvement of PFKFB3/iPFK2 in the suppressive effect of rosiglitazone on diet‐induced intestine inflammatory response
Author(s) -
Li Honggui,
Guo Xin,
Thomas Laura,
Sturino Joseph,
Wu Chaodong
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.341.5
Subject(s) - rosiglitazone , overnutrition , endocrinology , medicine , proinflammatory cytokine , inflammation , metabolic syndrome , type 2 diabetes , glucose homeostasis , wild type , receptor , small intestine , insulin , insulin resistance , chemistry , biology , diabetes mellitus , biochemistry , mutant , obesity , gene
Overnutrition is a causal factor of metabolic syndrome. However, little attention has been paid to the regulation of overnutrition‐related intestinal inflammation as it relates to metabolic syndrome. The objective of this study is to define the role of PFKFB3/iPFK2, a master regulator of nutrient metabolism, in regulating diet‐induced intestine inflammatory response in mice. For this purpose, mice were fed a high‐fat diet (HFD) and treated with or without rosiglitazone, an insulin‐sensitizer that also has an anti‐inflammatory effect. Compared to wild‐type littermates, mice that lack one allele of PFKFB3 (PFKFB3 +/− mice) displayed a significant increase in the expression of intestinal inflammatory markers such as toll‐like receptor 4 and proinflammatory cytokines on a HFD. These data indicate that disruption of PFKFB3 exacerbates diet‐induced intestine inflammatory response. When treated with rosiglitazone, the expression of the above inflammatory markers was markedly decreased in HFD‐fed wild‐type mice, and, to a lesser extent, in HFD‐fed PFKFB3 +/− mice. Additionally, treatment with rosiglitazone normalized systemic insulin sensitivity and glucose homeostasis in HFD‐fed wild‐type mice, but not in HFD‐fed PFKFB3 +/− mice. Therefore, PFKFB3/iPFK2 is involved in the suppressive effect of rosiglitazone on diet‐induced intestine inflammatory response.