Gene expression of the zinc transporter ZIP14 (SLC39a14) is affected by weight loss and metabolic status and associates with PPARγ in human adipose tissue and 3T3-L1 pre-adipocytes

Maxel, Trine; Smidt, Kamille; Bennetzen, Marianne; Cullberg, Karina B.; Fjeldborg, Karen; Lund, Sten; Pedersen, Steen B.; Rungby, Jørgen

doi:10.1186/s40608-015-0076-y

Cited by 26 publications

(24 citation statements)

References 53 publications

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“…For example, in the adipose tissue of Zip14 -KO mice, hypertrophy together with enhanced proinflammatory signaling is observed through activation of nuclear factor-kappaB (NF-κB) and the Janus-activating kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway, and this might contribute to obesity-induced insulin resistance [ 62 ]. Consistent with this idea, Zip14 expression is significantly reduced in obese individuals compared with non-obese individuals, and is increased markedly following weight loss [ 63 ].…”

Section: Zinc Distribution Affects Adipocyte Metabolismmentioning

confidence: 86%

Role of Zinc Homeostasis in the Pathogenesis of Diabetes and Obesity

Fukunaka

Fujitani

2018

IJMS

192

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: 86%

Role of Zinc Homeostasis in the Pathogenesis of Diabetes and Obesity

Fukunaka

Fujitani

2018

IJMS

192

108

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“…It has been revealed that obese patients were characterized by a significantly lower expression of Zip14 in subcutaneous adipose tissue, whereas a 10-week weight loss period significantly increased gene expression. Zip14 expression directly correlated with PPARy expression and HDL-C concentration, although being negatively associated with anthropometric markers of obesity, body fat percentage, HOMA-IR, blood glucose, insulin, and TG levels [ 126 ].…”

Section: Introductionmentioning

confidence: 99%

“…It has also been demonstrated that SLC39A14, a member of the ZIP protein subfamily, is induced during the early stages of adipogenesis, being associated with increased Zn uptake [ 126 ]. It is also notable that Zip14 regulates inflammatory signaling in adipocyte hypertrophy [ 129 ].…”

Section: Introductionmentioning

confidence: 99%

Zinc status is associated with inflammation, oxidative stress, lipid, and glucose metabolism

et al. 2017

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A number of studies have reported that zinc plays a substantial role in the development of metabolic syndrome, taking part in the regulation of cytokine expression, suppressing inflammation, and is also required to activate antioxidant enzymes that scavenge reactive oxygen species, reducing oxidative stress. Zinc also plays a role in the correct functioning of lipid and glucose metabolism, regulating and forming the expression of insulin. In numerous studies, zinc supplementation has been found to improve blood pressure, glucose, and LDL cholesterol serum level. Deeper knowledge of zinc’s properties may help in treating metabolic syndrome, thus protecting against stroke and angina pectoris, and ultimately against death.

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“… 17 It exists in at least two isoforms that differ from each other in the cation-binding domain. 18 Growing evidence shows the implications of SLC39A14 in various human malignancies. According to the ONCOMINE database, 19 SLC39A14 is indicated to be among the top 1% of genes underexpressed in hepatocellular carcinoma compared to normal liver, which was consistent with the findings of Franklin et al 20 The SLC39A14-exon4B transcript variants were identified as biomarkers of colorectal, gastric, and lung cancers which are known to have an aber-rantly activated WNT-signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Decreased expression of SLC39A14 is associated with tumor aggressiveness and biochemical recurrence of human prostate cancer

Xu¹,

Wang²,

Zhu³

et al. 2016

OTT

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ObjectiveSolute carrier family 39, member 14 (SLC39A14), has been identified as a potential biomarker for various cancers. However, its roles in prostate cancer (PCa) are still unclear. The aim of this study was to investigate the clinical significance of SLC39A14 in patients with PCa and its functions in malignant phenotypes of PCa cells.Patients and methodsSubcellular localization and expression pattern of SLC39A14 protein were examined by immunohistochemistry. Then, the associations of SLC39A14 expression with various clinicopathological features and clinical outcome of patients with PCa were statistically evaluated. Subsequently, the effects of SLC39A14 overexpression and knockdown on PCa cell proliferation and motility were, respectively, examined by Cell Counting Kit-8, transwell, and wound-healing assays.ResultsThe immunoreactive scores of SLC39A14 protein in human PCa tissues were significantly lower than those in normal prostate tissues. Based on the Taylor dataset, SLC39A14 downregulation occurred more frequently in patients with PCa with a higher Gleason score (P<0.001), advanced clinical stage (P=0.008), presence of metastasis (P=0.009), and prostate-specific antigen failure (P=0.006). More interestingly, the survival analysis identified SLC39A14 as an independent factor for predicting the biochemical recurrence-free survival of patients with PCa (P=0.017). Functionally, the enforced expression of SLC39A14 could suppress cell proliferation, invasion, and migration of PCa cell lines in vitro, which could be reversed by the knockdown of SLC39A14.ConclusionDecreased expression of SLC39A14 may lead to malignant phenotypes of PCa cells and aggressive tumor progression in patients with PCa. Importantly, SLC39A14 may function as a tumor suppressor and a biomarker for screening patients with biochemical recurrence following radical prostatectomy.

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Gene expression of the zinc transporter ZIP14 (SLC39a14) is affected by weight loss and metabolic status and associates with PPARγ in human adipose tissue and 3T3-L1 pre-adipocytes

Cited by 26 publications

References 53 publications

Role of Zinc Homeostasis in the Pathogenesis of Diabetes and Obesity

Role of Zinc Homeostasis in the Pathogenesis of Diabetes and Obesity

Zinc status is associated with inflammation, oxidative stress, lipid, and glucose metabolism

Decreased expression of SLC39A14 is associated with tumor aggressiveness and biochemical recurrence of human prostate cancer

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