Cisd2 modulates the differentiation and functioning of adipocytes by regulating intracellular Ca2+ homeostasis

Chih Hao Wang, Yi Fan Chen, Chia Yu Wu, Pei Chun Wu, Yi Long Huang, Cheng Heng Kao, Chao Hsiung Lin, Lung Sen Kao, Ting Fen Tsai, Yau Huei Wei

研究成果: 雜誌貢獻文章

40 引文 (Scopus)

摘要

CISD2 is a causative gene associated with Wolfram syndrome (WFS). However, it remains a mystery as to how the loss of CISD2 causes metabolic defects in patients with WFS. Investigation on the role played by Cisd2 in specific cell types may help us to resolve these underlying mechanisms. White adipose tissue (WAT) is central to the maintenance of energy metabolism and glucose homeostasis in humans. In this study, adipocyte-specific Cisd2 knockout (KO) mice showed impairment in the development of epididymal WAT (eWAT) in the cell autonomous manner. A lack of Cisd2 caused defects in the biogenesis and function of mitochondria during differentiation of adipocytes in vitro. Insulin-stimulated glucose uptake and secretion of adiponectin by the Cisd2 KO adipocytes were decreased. Moreover, Cisd2 deficiency increased the cytosolic level of Ca2+ and induced Ca2+-calcineurin-dependent signaling that inhibited adipogenesis. Importantly, Cisd2 was found to interact with Gimap5 on the mitochondrial and ER membranes and thereby modulate mitochondrial Ca2+ uptake associated with the maintenance of intracellular Ca2+ homeostasis in adipocytes. Thus, it would seem that Cisd2 plays an important role in intracellular Ca2+ homeostasis, which is required for the differentiation and functioning of adipocytes as well as the regulation of glucose homeostasis in mice.
原文英語
文章編號ddu193
頁(從 - 到)4770-4785
頁數16
期刊Human Molecular Genetics
23
發行號18
DOIs
出版狀態已發佈 - 2014

指紋

Adipocytes
Homeostasis
Wolfram Syndrome
White Adipose Tissue
Glucose
Maintenance
Adipogenesis
Calcineurin
Adiponectin
Mitochondrial Membranes
Knockout Mice
Energy Metabolism
Mitochondria
Insulin
Genes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology
  • Medicine(all)

引用此文

Cisd2 modulates the differentiation and functioning of adipocytes by regulating intracellular Ca2+ homeostasis. / Wang, Chih Hao; Chen, Yi Fan; Wu, Chia Yu; Wu, Pei Chun; Huang, Yi Long; Kao, Cheng Heng; Lin, Chao Hsiung; Kao, Lung Sen; Tsai, Ting Fen; Wei, Yau Huei.

於: Human Molecular Genetics, 卷 23, 編號 18, ddu193, 2014, p. 4770-4785.

研究成果: 雜誌貢獻文章

Wang, CH, Chen, YF, Wu, CY, Wu, PC, Huang, YL, Kao, CH, Lin, CH, Kao, LS, Tsai, TF & Wei, YH 2014, 'Cisd2 modulates the differentiation and functioning of adipocytes by regulating intracellular Ca2+ homeostasis', Human Molecular Genetics, 卷 23, 編號 18, ddu193, 頁 4770-4785. https://doi.org/10.1093/hmg/ddu193
Wang, Chih Hao ; Chen, Yi Fan ; Wu, Chia Yu ; Wu, Pei Chun ; Huang, Yi Long ; Kao, Cheng Heng ; Lin, Chao Hsiung ; Kao, Lung Sen ; Tsai, Ting Fen ; Wei, Yau Huei. / Cisd2 modulates the differentiation and functioning of adipocytes by regulating intracellular Ca2+ homeostasis. 於: Human Molecular Genetics. 2014 ; 卷 23, 編號 18. 頁 4770-4785.
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abstract = "CISD2 is a causative gene associated with Wolfram syndrome (WFS). However, it remains a mystery as to how the loss of CISD2 causes metabolic defects in patients with WFS. Investigation on the role played by Cisd2 in specific cell types may help us to resolve these underlying mechanisms. White adipose tissue (WAT) is central to the maintenance of energy metabolism and glucose homeostasis in humans. In this study, adipocyte-specific Cisd2 knockout (KO) mice showed impairment in the development of epididymal WAT (eWAT) in the cell autonomous manner. A lack of Cisd2 caused defects in the biogenesis and function of mitochondria during differentiation of adipocytes in vitro. Insulin-stimulated glucose uptake and secretion of adiponectin by the Cisd2 KO adipocytes were decreased. Moreover, Cisd2 deficiency increased the cytosolic level of Ca2+ and induced Ca2+-calcineurin-dependent signaling that inhibited adipogenesis. Importantly, Cisd2 was found to interact with Gimap5 on the mitochondrial and ER membranes and thereby modulate mitochondrial Ca2+ uptake associated with the maintenance of intracellular Ca2+ homeostasis in adipocytes. Thus, it would seem that Cisd2 plays an important role in intracellular Ca2+ homeostasis, which is required for the differentiation and functioning of adipocytes as well as the regulation of glucose homeostasis in mice.",
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