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Genistein and daidzein, typical soy isoflavones, inhibit TNF ‐α‐mediated downregulation of adiponectin expression via different mechanisms in 3 T 3‐ L 1 adipocytes
Author(s) -
Yanagisawa Masayoshi,
Sugiya Masahiro,
Iijima Hiroshi,
Nakagome Izumi,
Hirono Shuichi,
Tsuda Takanori
Publication year - 2012
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201200284
Subject(s) - downregulation and upregulation , adiponectin , genistein , endocrinology , daidzein , medicine , isoflavones , tumor necrosis factor alpha , chemistry , biology , insulin , insulin resistance , biochemistry , gene
Scope Previous reports suggest that soy isoflavones have multiple biological functions and may help to restore adiponectin expression and insulin sensitivity. However, little is known about whether soy isoflavones can inhibit the downregulation of adiponectin and their molecular mechanisms. In the present study, we demonstrate that genistein ( G en) or daidzein ( D ai) can significantly inhibit the downregulation of adiponectin expression via unique and different molecular mechanisms. Methods and results Pretreatment with G en or D ai significantly inhibited the tumor necrosis factor‐alpha ( TNF ‐α)‐mediated downregulation of adiponectin expression in 3 T 3‐ L 1 adipocytes. G en inhibited the TNF ‐α‐induced c‐ J un‐ NH 2 ‐terminal kinase ( JNK ) signaling that is involved in adiponectin expression. Molecular docking studies based on JNK 1 with G en or D ai clearly supported our experimental results. However, D ai did not significantly inhibit JNK signaling. D ai did, however, inhibit the TNF ‐α‐induced downregulation of forkhead box‐containg protein O1, which is also involved in adiponectin expression. Conclusion These data demonstrate that: (i) both G en and D ai significantly inhibit the TNF ‐α‐mediated downregulation of adiponectin in adipocytes; (ii) G en is an effective inhibitor of JNK activation, thus inhibiting the TNF ‐α‐mediated downregulation of adiponectin; and (iii) D ai can inhibit the downregulation of adiponectin by restoring the TNF ‐α‐mediated reduction of forkhead box‐containg protein O1 protein expression.