Ro Hyo-Sung, Zhang Lei, Majdalawieh Amin, Kim Sung-Woo, Wu Xue, Lyons Peter J, Webber Chris, Ma Hong, Reidy Shannon P, Boudreau Aaron, Miller Jessica R, Mitchell Patricia, McLeod Roger S
Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, Nova Scotia, Canada.
Obesity (Silver Spring). 2007 Feb;15(2):288-302. doi: 10.1038/oby.2007.569.
To determine whether adipocyte enhancer binding protein (AEBP) 1, a transcriptional repressor that is down-regulated during adipogenesis, functions as a critical regulator of adipose tissue homeostasis through modulation of phosphatase and tensin homolog deleted on chromosome ten (PTEN) tumor suppressor activity and mitogen-activated protein kinase (MAPK) activation.
We examined whether AEBP1 physically interacts with PTEN in 3T3-L1 cells by coimmunoprecipitation analysis. We generated AEBP1-null mice and examined the physiological role of AEBP1 as a key modulator of in vivo adiposity. Using adipose tissue from wild-type and AEBP1-null animals, we examined whether AEBP1 affects PTEN protein level.
AEBP1 interacts with PTEN, and deficiency of AEBP1 increases adipose tissue PTEN mass. AEBP1-null mice have reduced adipose tissue mass and enhanced apoptosis with suppressed survival signal. Primary pre-adipocytes from AEBP1-null adipose tissues exhibit lower basal MAPK activity with defective proliferative potential. AEBP1-null mice are also resistant to diet-induced obesity, suggesting a regulatory role for AEBP1 in energy homeostasis.
Our results suggest that AEBP1 negatively regulates adipose tissue PTEN levels, in conjunction with its role in proliferation and differentiation of pre-adipocytes, as a key functional role in modulation of in vivo adiposity.
确定脂肪细胞增强子结合蛋白（AEBP）1，一种在脂肪生成过程中表达下调的转录抑制因子，是否通过调节10号染色体缺失的磷酸酶和张力蛋白同源物（PTEN）肿瘤抑制活性以及丝裂原活化蛋白激酶（MAPK）激活，作为脂肪组织稳态的关键调节因子发挥作用。
我们通过免疫共沉淀分析检测了AEBP1在3T3-L1细胞中是否与PTEN发生物理相互作用。我们构建了AEBP1基因敲除小鼠，并研究了AEBP1作为体内肥胖关键调节因子的生理作用。利用野生型和AEBP1基因敲除动物的脂肪组织，我们检测了AEBP1是否影响PTEN蛋白水平。
AEBP1与PTEN相互作用，AEBP1缺乏会增加脂肪组织中PTEN的含量。AEBP1基因敲除小鼠的脂肪组织质量减少，凋亡增加，生存信号受到抑制。来自AEBP1基因敲除脂肪组织的原代前脂肪细胞表现出较低的基础MAPK活性，增殖潜力存在缺陷。AEBP1基因敲除小鼠也对饮食诱导的肥胖具有抗性，这表明AEBP1在能量稳态中具有调节作用。
我们的结果表明，AEBP1负向调节脂肪组织中PTEN的水平，并且在脂肪前体细胞的增殖和分化中发挥作用，这是其调节体内肥胖的关键功能。
