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Sulfuretin Prevents Obesity and Metabolic Diseases in Diet Induced Obese Mice

  • Kim, Suji (Department of Food Science and Biotechnology, Sungkyunkwan University) ;
  • Song, No-Joon (Department of Food Science and Biotechnology, Sungkyunkwan University) ;
  • Chang, Seo-Hyuk (Department of Food Science and Biotechnology, Sungkyunkwan University) ;
  • Bahn, Gahee (School of Pharmacy, Sungkyunkwan University) ;
  • Choi, Yuri (School of Pharmacy, Sungkyunkwan University) ;
  • Rhee, Dong- Kwon (School of Pharmacy, Sungkyunkwan University) ;
  • Yun, Ui Jeong (Department of Food Science and Biotechnology, Sungkyunkwan University) ;
  • Choi, Jinhee (Department of Food Science and Biotechnology, Sungkyunkwan University) ;
  • Lee, Jeon (Department of Food Science and Biotechnology, Sungkyunkwan University) ;
  • Yoo, Jae Hyuk (Department of Medicine, Program in Molecular Medicine, University of Utah) ;
  • Shin, Donghan (Department of Medicine, Program in Molecular Medicine, University of Utah) ;
  • Park, Ki-Moon (Department of Food Science and Biotechnology, Sungkyunkwan University) ;
  • Kang, Hee (Department of Oriental Medical Science, Graduate School of East-West Medicine, Kyunghee University) ;
  • Lee, Sukchan (Department of Integrative Biotechnology, Sungkyunkwan University) ;
  • Ku, Jin-Mo (Biomaterials Research and Development Team, Bio-Center, Gyeonggido Business Science Accelerator) ;
  • Cho, Yoon Shin (Department of Biomedical Science, Hallym University) ;
  • Park, Kye Won (Department of Food Science and Biotechnology, Sungkyunkwan University)
  • Received : 2018.05.20
  • Accepted : 2018.06.26
  • Published : 2019.01.01

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

References

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