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. 2007 Nov 16;363(2):355-60.
doi: 10.1016/j.bbrc.2007.08.167. Epub 2007 Sep 6.

Unexpected blockade of adipocyte differentiation by K-7174: implication for endoplasmic reticulum stress

Tsuyoshi Shimada  1 , Nobuhiko Hiramatsu, Maro Okamura, Kunihiro Hayakawa, Ayumi Kasai, Jian Yao, Masanori Kitamura
Affiliations

Unexpected blockade of adipocyte differentiation by K-7174: implication for endoplasmic reticulum stress

Tsuyoshi Shimada et al. Biochem Biophys Res Commun. .

Abstract

Preadipocytes constitutively express GATA-2 and GATA-3 that are required to halt the cells at the undifferentiated stage. However, we unexpectedly found that K-7174, a GATA-specific inhibitor, did not induce but rather inhibited differentiation of 3T3-L1 preadipocytes. It was associated with lack of lipid accumulation, blunted expression of adipocyte markers including adiponectin and peroxisome proliferator-activated receptor gamma (PPARgamma), and sustained expression of a preadipocyte marker monocyte chemoattractant protein 1 (MCP-1). Subsequent experiments revealed that K-7174 had the potential to induce endoplasmic reticulum (ER) stress evidenced by induction of GRP78 and CHOP. Other inducers of ER stress completely reproduced the effects of K-7174 including suppression of lipid accumulation, blockade of induction of adiponection and PPARgamma and maintenance of MCP-1 expression. These results indicated a possibility that ER stress suppresses adipocyte differentiation and that GATA inhibitor K-7174 has the potential for interfering with adipogenesis through induction of ER stress.

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