Biomol Ther  
Sulfuretin Prevents Obesity and Metabolic Diseases in Diet Induced Obese Mice
Suji Kim1, No-Joon Song1, Seo-Hyuk Chang1, Gahee Bahn2, Yuri Choi2, Dong- Kwon Rhee2, Ui Jeong Yun1, Jinhee Choi1, Jeon Lee1, Jae Hyuk Yoo3, Donghan Shin3, Ki-Moon Park1, Hee Kang4, Sukchan Lee5, Jin-Mo Ku6, Yoon Shin Cho7 and Kye Won Park1,*
1Department of Food Science and Biotechnology, Sungkyunkwan University, Suwon 16419, Republic of Korea
2School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea
3Department of Medicine, Program in Molecular Medicine, University of Utah, Salt Lake City, UT 84112, USA
4Department of Oriental Medical Science, Graduate School of East-West Medicine, Kyunghee University, Yongin 17104, Republic of Korea
5Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Republic of Korea
6Biomaterials Research and Development Team, Bio-Center, Gyeonggido Business Science Accelerator, Suwon 16229, Republic of Korea
7Department of Biomedical Science, Hallym University, Chuncheon 24252, Republic of Korea
E-mail: kwpark@skku.edu
Tel: +82-31-290-7804, Fax: +82-31-290-7882
Received: May 20, 2018; Revised: June 19, 2018; Accepted: June 26, 2018; Published online: August 22, 2018.
© The Korean Society of Applied Pharmacology. All rights reserved.

Abstract
The global obesity epidemic and associated metabolic diseases require alternative biological targets for new therapeutic strategies. In this study, we show that a phytochemical sulfuretin suppressed adipocyte differentiation of preadipocytes and administration of sulfuretin to high fat diet-fed obese mice prevented obesity and increased insulin sensitivity. These effects were associated with a suppressed expression of inflammatory markers, induced expression of adiponectin, and increased levels of phosphorylated ERK and AKT. To elucidate the molecular mechanism of sulfuretin in adipocytes, we performed microarray analysis and identified activating transcription factor 3 (Atf3) as a sulfuretin-responsive gene. Sulfuretin elevated Atf3 mRNA and protein levels in white adipose tissue and adipocytes. Consistently, deficiency of Atf3 promoted lipid accumulation and the expression of adipocyte markers. Sulfuretin’s but not resveratrol’s anti-adipogenic effects were diminished in Atf3 deficient cells, indicating that Atf3 is an essential factor in the effects of sulfuretin. These results highlight the usefulness of sulfuretin as a new anti-obesity intervention for the prevention of obesity and its associated metabolic diseases.
Keywords: Sulfuretin, Obesity, Adipocyte, Metabolic diseases, Diabetes, Atf3


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