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.