Biomol Ther.  2019 Jan;27(1):107-116. 10.4062/biomolther.2018.090.

Sulfuretin Prevents Obesity and Metabolic Diseases in Diet Induced Obese Mice

Affiliations
  • 1Department of Food Science and Biotechnology, Sungkyunkwan University, Suwon 16419, Republic of Korea. kwpark@skku.edu
  • 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.

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.

Keyword

Sulfuretin; Obesity; Adipocyte; Metabolic diseases; Diabetes; Atf3

MeSH Terms

Activating Transcription Factor 3
Adipocytes
Adiponectin
Adipose Tissue, White
Animals
Diet*
Insulin Resistance
Metabolic Diseases*
Mice
Mice, Obese*
Microarray Analysis
Obesity*
RNA, Messenger
Activating Transcription Factor 3
Adiponectin
RNA, Messenger
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