Kim Won Kon, Oh Kyoung-Jin, Choi Hye-Ryung, Park Anna, Han Baek Soo, Chi Seung-Wook, Kim Seung Jun, Bae Kwang-Hee, Lee Sang Chul
Functional Genomics Research Center, KRIBB, Daejeon, 305-806, Republic of Korea; Department of Functional Genomics, University of Science and Technology of Korea, Daejeon, 305-806, Republic of Korea.
Functional Genomics Research Center, KRIBB, Daejeon, 305-806, Republic of Korea.
Mol Cell Endocrinol. 2015 Nov 15;416:70-6. doi: 10.1016/j.mce.2015.08.023. Epub 2015 Aug 29.
Brown fat has been highlight as a new therapeutic target for treatment of obesity and diabetes. However, molecular mechanism underlying brown adipogenesis are not fully understood. Here, we identified that MAP kinase phosphatase 3 (MKP3) has a novel role as regulator of brown adipocyte differentiation. The expression of MKP3 was significantly decreased during the early stage(s) of brown adipocyte differentiation in HIB-1B cells and primary cells. Ectopic expression of MKP3 led to reduced brown adipocyte differentiation, whereas depletion of MKP3 significantly enhanced the differentiation of primary brown preadipocytes. Consistently, we found an increased brown adipocyte differentiation in MKP3-null MEF cells. These inhibitory effects of MKP3 could be resulted via the temporal regulation of Erk activation. In recent, it was reported that MKP3 deficient mice are resistant to diet-induced obesity, and display enhanced energy expenditure. Taken together, we suggest that MKP3 could be an important factor in the regulation of brown adipocyte differentiation.
棕色脂肪已被视为治疗肥胖症和糖尿病的新治疗靶点。然而，棕色脂肪生成的分子机制尚未完全明确。在此，我们发现丝裂原活化蛋白激酶磷酸酶3（MKP3）作为棕色脂肪细胞分化的调节因子具有新的作用。在HIB-1B细胞和原代细胞中，棕色脂肪细胞分化早期阶段MKP3的表达显著降低。MKP3的异位表达导致棕色脂肪细胞分化减少，而敲除MKP3则显著增强原代棕色前脂肪细胞的分化。同样，我们发现MKP3基因敲除的小鼠胚胎成纤维细胞（MEF）中棕色脂肪细胞分化增加。MKP3的这些抑制作用可能是通过对细胞外信号调节激酶（Erk）激活的时间调控来实现的。最近有报道称，MKP3缺陷小鼠对饮食诱导的肥胖具有抗性，并表现出能量消耗增加。综上所述，我们认为MKP3可能是调节棕色脂肪细胞分化的重要因素。
