Zinc transporter ZIP13 suppresses beige adipocyte biogenesis and energy expenditure by regulating C/EBP-β expression

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; Fujitani, Yoshio

doi:10.1371/journal.pgen.1006950

Cited by 52 publications

(45 citation statements)

References 56 publications

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“…Therefore, we aimed to clarify the roles of ZIP13 in fat tissue. During our investigation, we found that Zip13 -KO inguinal WAT had a high number of functional beige adipocytes [ 74 ]. Furthermore, Zip13 -KO mice showed a significantly higher oxygen consumption rate than wild-type mice, although there were no differences in food intake, suggesting that Zip13 -KO mice have a tendency to not gain weight.…”

Section: Zinc Distribution Affects Adipocyte Metabolismmentioning

confidence: 99%

Role of Zinc Homeostasis in the Pathogenesis of Diabetes and Obesity

Fukunaka

Fujitani

2018

IJMS

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187

108

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Zinc deficiency is a risk factor for obesity and diabetes. However, until recently, the underlying molecular mechanisms remained unclear. The breakthrough discovery that the common polymorphism in zinc transporter SLC30A8/ZnT8 may increase susceptibility to type 2 diabetes provided novel insights into the role of zinc in diabetes. Our group and others showed that altered ZnT8 function may be involved in the pathogenesis of type 2 diabetes, indicating that the precise control of zinc homeostasis is crucial for maintaining health and preventing various diseases, including lifestyle-associated diseases. Recently, the role of the zinc transporter ZIP13 in the regulation of beige adipocyte biogenesis was clarified, which indicated zinc homeostasis regulation as a possible therapeutic target for obesity and metabolic syndrome. Here we review advances in the role of zinc homeostasis in the pathophysiology of diabetes, and propose that inadequate zinc distribution may affect the onset of diabetes and metabolic diseases by regulating various critical biological events.

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Section: Zinc Distribution Affects Adipocyte Metabolismmentioning

confidence: 99%

Role of Zinc Homeostasis in the Pathogenesis of Diabetes and Obesity

Fukunaka

Fujitani

2018

IJMS

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187

108

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“…A peptide derived from VGF (VGF nerve growth factor inducible) helps control insulin secretion (37). DLK1 (Delta Like Non-Canonical Notch Ligand 1) (38) induces insulin synthesis and secretion, and SLC39A13 (Solute Carrier Family 39 Member 13) is a transporter protein for Zn ++ , which could play a role in insulin storage, secretion, and activity (39). In searching for an example of INS expression-dependent interchromosomal transvection that affected insulin metabolism, our attention was drawn to SSTR5-AS1, which codes for an antisense RNA to SSTR5.…”

Section: Expression Levels Of Contacted Genes Affected By Ins Expressionmentioning

confidence: 99%

Insulin promoter in human pancreatic β cells contacts diabetes susceptibility loci and regulates genes affecting insulin metabolism

Jian

Felsenfeld

2018

Proc. Natl. Acad. Sci. U.S.A.

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Both type 1 and type 2 diabetes involve a complex interplay between genetic, epigenetic, and environmental factors. Our laboratory has been interested in the physical interactions, in nuclei of human pancreatic β cells, between the insulin ( gene and other genes that are involved in insulin metabolism. We have identified, using Circularized Chromosome Conformation Capture (4C), many physical contacts in a human pancreatic β cell line between the promoter on chromosome 11 and sites on most other chromosomes. Many of these contacts are associated with type 1 or type 2 diabetes susceptibility loci. To determine whether physical contact is correlated with an ability of the locus to affect expression of these genes, we knock down expression by targeting the promoter; 259 genes are either up or down-regulated. Of these, 46 make physical contact with We analyze a subset of the contacted genes and show that all are associated with acetylation of histone H3 lysine 27, a marker of actively expressed genes. To demonstrate the usefulness of this approach in revealing regulatory pathways, we identify from among the contacted sites the previously uncharacterized gene and show that it plays an important role in controlling the effect of somatostatin-28 on insulin secretion. These results are consistent with models in which clustering of genes supports transcriptional activity. This may be a particularly important mechanism in pancreatic β cells and in other cells where a small subset of genes is expressed at high levels.

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“…These patients exhibited significantly decreased white fat mass. Recently, Fukunaka et al demonstrated that ZIP13-mediated Zn transport plays a critical role in suppressing adipocyte browning by reducing C/EBP-β proteins [ 84 ], which are discussed in this issue by Fukunaka and Fujitani. The molecular mechanism of the pathogenesis induced by the mutations is described below.…”

Section: Overview Of Mammalian Zrt- and Irt-like Protein (Zip) Tramentioning

confidence: 99%

Recent Advances in the Role of SLC39A/ZIP Zinc Transporters In Vivo

Takagishi

Hara

Fukada

2017

IJMS

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Zinc (Zn), which is an essential trace element, is involved in numerous mammalian physiological events; therefore, either a deficiency or excess of Zn impairs cellular machineries and influences physiological events, such as systemic growth, bone homeostasis, skin formation, immune responses, endocrine function, and neuronal function. Zn transporters are thought to mainly contribute to Zn homeostasis within cells and in the whole body. Recent genetic, cellular, and molecular studies of Zn transporters highlight the dynamic role of Zn as a signaling mediator linking several cellular events and signaling pathways. Dysfunction in Zn transporters causes various diseases. This review aims to provide an update of Zn transporters and Zn signaling studies and discusses the remaining questions and future directions by focusing on recent progress in determining the roles of SLC39A/ZIP family members in vivo.

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Zinc transporter ZIP13 suppresses beige adipocyte biogenesis and energy expenditure by regulating C/EBP-β expression

Cited by 52 publications

References 56 publications

Role of Zinc Homeostasis in the Pathogenesis of Diabetes and Obesity

Role of Zinc Homeostasis in the Pathogenesis of Diabetes and Obesity

Insulin promoter in human pancreatic β cells contacts diabetes susceptibility loci and regulates genes affecting insulin metabolism

Recent Advances in the Role of SLC39A/ZIP Zinc Transporters In Vivo

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