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Transcriptional factor‐X and related small molecule herbal inducer, ST32DB, against obesity and metabolic dysfunction through lipogenic transcription factor ChREBP and white adipocytes trans‐differentiation axis
Author(s) -
Chen HsiHsien,
Lin Heng
Publication year - 2017
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.31.1_supplement.lb717
Subject(s) - lipogenesis , endocrinology , medicine , adipogenesis , lipolysis , white adipose tissue , adipocyte , inducer , steatosis , metabolic syndrome , lipid metabolism , chemistry , biology , adipose tissue , obesity , biochemistry , gene
Altering the balance between lipogenesis/lipolysis or altered white fat remodeling is a potential strategy for treating obesity and metabolic syndrome. Here, we demonstrate that genetic deletion of Transcriptional factor‐X (TFX) decreased energy expenditure but increased body weight, insulin resistance and hepatic steatosis during high‐fat diet regimens, in addition, restored TFX expression by AAV‐mediated in TFX knockout mice were abrogate these metabolic changes. In vitro study in 3T3‐L1 adipocytes also shown that TFX‐overexpressing exhibited less lipid accumulation with diminished expression of adipogenesis, lypogenesis and inflammation‐related genes but increased loogenesis, β‐oxidation and brown/beige genes as compared through ChREBP and SCD1 dependent pathway. Finally, the beneficial metabolic change, thermogenesis elicited, reduced lipogenesis and increased lypolysis by a new finding TFX inducer selected by TFX stable clone in 3T3‐L1 adipocytes were emerged in normal mice but in TFX knock out mice when feeding high fat diet. In addition, consistent results between in vitro and in mice. Overall, our finding identify TFX and a new TFX single compound inducer from herbal as a regulator of lipogenesis/lipolysis balance and enhance energy expenditure and mediate adipocyte differentiation from white fat to brown fat through CHREBP and SCD1 pathway represents a possible therapeutic strategy go treat obesity and obesity induced metabolism syndrome.