Journal
BIOMOLECULES & THERAPEUTICS
Volume 27, Issue 1, Pages 107-116Publisher
KOREAN SOC APPLIED PHARMACOLOGY
DOI: 10.4062/biomolther.2018.090
Keywords
Sulfuretin; Obesity; Adipocyte; Metabolic diseases; Diabetes; Atf3
Funding
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education, Science, and Technology [NRF-2016M3A9B6903451, NRF-2017R1A2B4002005, NRF-2017R1A6A3A110295845]
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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.
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