ATF3가 adipocyte hypoxia에 의한 adipocyte dysfunction ( adipocyte의 differentiation 저해, adipocyte mitochondria dysfunction, adipocyte inflammation 증가)에 중요하게 관여함을 밝혔음. ⒤ 비만 당뇨쥐의 지방조직에서 adipocyte hypoxia, ATF3가 증가하는 반면, adipocyte function은 감소 하였음 (ⅱ) adipocye cell 3T3-L1을 hypoxic 조건으로 처리한 결과, adipocyte dif
ATF3가 adipocyte hypoxia에 의한 adipocyte dysfunction ( adipocyte의 differentiation 저해, adipocyte mitochondria dysfunction, adipocyte inflammation 증가)에 중요하게 관여함을 밝혔음. ⒤ 비만 당뇨쥐의 지방조직에서 adipocyte hypoxia, ATF3가 증가하는 반면, adipocyte function은 감소 하였음 (ⅱ) adipocye cell 3T3-L1을 hypoxic 조건으로 처리한 결과, adipocyte differentiarion과 미토 콘드리아의 기능은 저해되는 반면 inflammation은 증가하였음 (ⅲ) ATF3을 knockdown 시킨 3T3-L1 에서 hypoxia에 의한 adidocyte dysfunction은 회복되었음 (iv) ATF3 지방조직 특이적으로 과발현시킨 동물에서 high fat diet (HFD)에 의한 adipocyte dysfunction은 증가하였고, insulin sensitivity은 감소하였음 (ⅳ) ATF3에 의한 C/EBP-α 의 promoter를 분석하여 ATF3가 C/EBP-α 를 저해하여 adipocyte differentiation을 억제함을 밝혔음
Abstract▼
□ The purpose of study : This study was to characterize the role of ATF3 in obesity hypoxia induced-adipocyte dysfunction. □ The method of the study : To this end, we investigated the adipocyte differentiation, mitochondria function-related factors, inflammatory cytokines in 3T3-L1 cells treated
□ The purpose of study : This study was to characterize the role of ATF3 in obesity hypoxia induced-adipocyte dysfunction. □ The method of the study : To this end, we investigated the adipocyte differentiation, mitochondria function-related factors, inflammatory cytokines in 3T3-L1 cells treated with CoCl2 or incubated in 2% O2 hypoxic chamber. And, to elucidate the involvement of ATF3 in adipocyte hypoxia-induced adipocyte dysfunction, we also investigated the adipocyte differentiation, mitochondria function-related factors, inflammatory cytokines in ATF3 knockdowned-3T3-L1 cells. Furthermore, we also examined adipocyte dysfunction in adipocyte specific ATF3 overexpressed transgenic mice to confirm the role of ATF3 in obesity-induced adipocyte dysfunction. □ The result of the study : ？ Both ATF3 and HIF1-α were increased in adipose tissue of obese db/db mice compared to lean mice. Mitochondria function-related factors NRF-1, COX-1, COX-2, SOD were decreased, whereas inflammatory cytokines TNF-1α , IL-6 were increased in adipose tissue of the mice. ？ Adipocyte differentiation, mitochondria function-related factors (NRF-1, COX-1, COX-2, SOD), adiponectin were reduced in 3T3-L1 cells under hypoxic conditions (CoCl2 & 2% O2), whereas TNF-1α , IL-6 were increased. However, ATF3 knockdown prevented the variations in hypoxic 3T3-L1 cells. ？ Furthermore, mitochondria function-related factors, adiponectin were decreased in adipose tissue of the transgenic mice, and the insulin sensitivity was reduced in the transgenic mice ？ ATF3 binds to promoter region of C/EBP-α and repressed the promoter activity, indicating that ATF3 inhibits adipocyte differentiation through downregulation of C/EBP-α
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