Echinomycin inhibits adipogenesis in 3T3-L1 cells in a HIF-independent manner.
Junna YamaguchiTetsuhiro TanakaHisako SaitoSeitaro NomuraHiroyuki AburataniHironori WakiTakashi KadowakiMasaomi NangakuPublished in: Scientific reports (2017)
Obesity is a risk factor for many diseases including diabetes, cancer, cardiovascular disease, and chronic kidney disease. Obesity is characterized by the expansion of white adipose tissue (WAT). Hypertrophy and hyperplasia of adipocytes cause tissue hypoxia followed by inflammation and fibrosis. Its trigger, preadipocyte differentiation into mature adipocytes, is finely regulated by transcription factors, signal molecules, and cofactors. We found that echinomycin, a potent HIF-1 inhibitor, completely inhibited adipogenesis in 3T3-L1 WAT preadipocytes by affecting the early phase of mitotic clonal expansion. The dose required to exert the effect was surprisingly low and the time was short. Interestingly, its inhibitory effect was independent of HIF-1 pathways. Time-course DNA microarray analysis of drug-treated and untreated preadipocytes extracted a major transcription factor, CCAAT/enhancer-protein β, as a key target of echinomycin. Echinomycin also inhibited adipogenesis and body weight gain in high fat diet mice. These findings highlight a novel role of echinomycin in suppressing adipocyte differentiation and offer a new therapeutic strategy against obesity and diabetes.
Keyphrases
- high fat diet induced
- insulin resistance
- high fat diet
- adipose tissue
- transcription factor
- type diabetes
- cardiovascular disease
- weight gain
- glycemic control
- metabolic syndrome
- skeletal muscle
- endothelial cells
- chronic kidney disease
- body mass index
- induced apoptosis
- dna binding
- weight loss
- birth weight
- cell cycle arrest
- papillary thyroid
- signaling pathway
- single molecule
- cell death
- physical activity
- small molecule
- emergency department
- endoplasmic reticulum stress
- coronary artery disease
- squamous cell carcinoma
- young adults
- genome wide identification
- cardiovascular events
- gestational age
- electronic health record