Yuqiao Xu1, Yu Gu1, Gang Liu2, Feng Zhang1, Jie Li1, Fang Liu1, Zhiwen Zhang1, Jing Ye3, Qing Li4. 1. State Key Laboratory of Cancer Biology and Department of Pathology, Xijing Hospital, Fourth Military Medical University, No.169 Changle West Road, Xi'an 710032, PR China. 2. Department of Plastic and Burns, Fourth Military Medical University, No.169 Changle West Road, Xi'an 710032, PR China. 3. State Key Laboratory of Cancer Biology and Department of Pathology, Xijing Hospital, Fourth Military Medical University, No.169 Changle West Road, Xi'an 710032, PR China. Electronic address: yejing@fmmu.edu.cn. 4. State Key Laboratory of Cancer Biology and Department of Pathology, Xijing Hospital, Fourth Military Medical University, No.169 Changle West Road, Xi'an 710032, PR China. Electronic address: liqing@fmmu.edu.cn.
Abstract
BACKGROUND: We previously showed that Cidec was localized on the surface of lipid droplets and could promote the differentiation of human adipocytes, but the molecular mechanism was still unknown. METHODS & RESULTS: In this study, we first sought to identify proteins that interact with Cidec using yeast two-hybrid system. The results revealed that Cidec could directly interact with AMPKα1 subunit. We further showed that AMPKα levels decreased while Cidec increased during the adipogenic differentiation of human adipocytes. Meanwhile, we observed that the increased Cidec could reduce AMPKα level in adipocytes, and the downregulation of AMPKα could help to promote the differentiation of adipocytes. The results of co-immunoprecipitation and immunofluorescent proved that Cidec biochemically interacted and co-localized with AMPKα1, which meant Cidec was a regulator for AMPKα stability through an ubiquitin-proteasome pathway. CONCLUSION: Our data suggested that Cidec could interact with and down-regulate AMPKα through an ubiquitin-proteasome degradation pathway, which provided a possible mechanism of Cidec in promoting human adipocytes differentiation. GENERAL SIGNIFICANCE: Our work proposed a new possible mechanism for human adipogenesis, and also provided a potential role of AMPKα as a target in treating obesity or obesity-related diseases.
BACKGROUND: We previously showed that Cidec was localized on the surface of lipid droplets and could promote the differentiation of human adipocytes, but the molecular mechanism was still unknown. METHODS & RESULTS: In this study, we first sought to identify proteins that interact with Cidec using yeast two-hybrid system. The results revealed that Cidec could directly interact with AMPKα1 subunit. We further showed that AMPKα levels decreased while Cidec increased during the adipogenic differentiation of human adipocytes. Meanwhile, we observed that the increased Cidec could reduce AMPKα level in adipocytes, and the downregulation of AMPKα could help to promote the differentiation of adipocytes. The results of co-immunoprecipitation and immunofluorescent proved that Cidec biochemically interacted and co-localized with AMPKα1, which meant Cidec was a regulator for AMPKα stability through an ubiquitin-proteasome pathway. CONCLUSION: Our data suggested that Cidec could interact with and down-regulate AMPKα through an ubiquitin-proteasome degradation pathway, which provided a possible mechanism of Cidec in promoting human adipocytes differentiation. GENERAL SIGNIFICANCE: Our work proposed a new possible mechanism for human adipogenesis, and also provided a potential role of AMPKα as a target in treating obesity or obesity-related diseases.
Authors: James Denvir; Goran Boskovic; Jun Fan; Donald A Primerano; Jacaline K Parkman; Jung Han Kim Journal: BMC Genomics Date: 2016-11-11 Impact factor: 3.969
Authors: Jonathan G Boucher; Rémi Gagné; Andrea Rowan-Carroll; Adèle Boudreau; Carole L Yauk; Ella Atlas Journal: PLoS One Date: 2016-09-29 Impact factor: 3.240