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- Title
Zinc transporter ZIP13 suppresses beige adipocyte biogenesis and energy expenditure by regulating C/EBP-β expression.
- Authors
Fukunaka, Ayako; Fukada, Toshiyuki; Bhin, Jinhyuk; Suzuki, Luka; Tsuzuki, Takamasa; Takamine, Yuri; Bin, Bum-Ho; Yoshihara, Toshinori; Ichinoseki-Sekine, Noriko; Naito, Hisashi; Miyatsuka, Takeshi; Takamiya, Shinzaburo; Sasaki, Tsutomu; Inagaki, Takeshi; Kitamura, Tadahiro; Kajimura, Shingo; Watada, Hirotaka; Fujitani, Yoshio
- Abstract
Given the relevance of beige adipocytes in adult humans, a better understanding of the molecular circuits involved in beige adipocyte biogenesis has provided new insight into human brown adipocyte biology. Genetic mutations in SLC39A13/ZIP13, a member of zinc transporter family, are known to reduce adipose tissue mass in humans; however, the underlying mechanisms remains unknown. Here, we demonstrate that the Zip13-deficient mouse shows enhanced beige adipocyte biogenesis and energy expenditure, and shows ameliorated diet-induced obesity and insulin resistance. Both gain- and loss-of-function studies showed that an accumulation of the CCAAT/enhancer binding protein-β (C/EBP-β) protein, which cooperates with dominant transcriptional co-regulator PR domain containing 16 (PRDM16) to determine brown/beige adipocyte lineage, is essential for the enhanced adipocyte browning caused by the loss of ZIP13. Furthermore, ZIP13-mediated zinc transport is a prerequisite for degrading the C/EBP-β protein to inhibit adipocyte browning. Thus, our data reveal an unexpected association between zinc homeostasis and beige adipocyte biogenesis, which may contribute significantly to the development of new therapies for obesity and metabolic syndrome.
- Subjects
ZINC transporters; FAT cells; CELL membrane formation; CALORIC expenditure; OBESITY; CARRIER proteins; METABOLIC syndrome
- Publication
PLoS Genetics, 2017, Vol 13, Issue 8, p1
- ISSN
1553-7390
- Publication type
Article
- DOI
10.1371/journal.pgen.1006950