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.

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

doi:10.1186/s40608-015-0076-y

Trine Maxel, Marianne Bennetzen + Show 7 more

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https://doi.org/10.1186/s40608-015-0076-y

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Abstract

BackgroundThe expansion and function of adipose tissue are important during the development of insulin resistance and inflammation in obesity. Zinc dyshomeostasis is common in obese individuals. In the liver, zinc influx transporter ZIP14, affects proliferation and glucose metabolism but the role of ZIP14 in adipose tissue is still unknown. This study investigates ZIP14 gene expression in human adipose tissue before and after weight loss as well as the regulation of ZIP14 during early adipogenesis.MethodsFourteen obese individuals were investigated before and after a 10 week weight loss intervention and compared to 14 non-obese controls. Gene expressions of ZIP14 and peroxisome proliferator-activated receptor γ (PPARγ) were measured in subcutaneous adipose tissue and correlated with metabolic and inflammatory markers. Further, we investigated gene expression of ZIP14 and PPARγ during early adipogenesis of 3T3-L1 pre-adipocytes, together with an in silico analysis of PPARγ binding motifs in the promoter sequence of ZIP14.ResultsZIP14 was down-regulated in obese individuals compared to non-obese controls (p = 0.0007) and was up-regulated after weight loss (p = 0.0005). Several metabolic markers of clinical importance, including body mass index, triglyceride, and insulin resistance, were inversely correlated with ZIP14. During early adipogensis an up-regulation of ZIP14 gene expression was found. PPARγ gene expression was positively correlated with the ZIP14 gene expression in both adipose tissue and during adipogenesis. However, in silico analysis revealed that the ZIP14 promoter does not contain PPARγ-binding motifs.ConclusionsWe hypothesize that ZIP14-mediated zinc influx might directly influence PPARγ activity and that ZIP14 may regulate expansion and function of adipose tissue and serve as a potential biomarker for metabolic stress.Electronic supplementary materialThe online version of this article (doi:10.1186/s40608-015-0076-y) contains supplementary material, which is available to authorized users.

Highlights

The expansion and function of adipose tissue are important during the development of insulin resistance and inflammation in obesity
The aim of this study was to examine the expression of ZIP14 in vivo in human adipose tissue relating the expression of this gene to body weight and clinical relevant markers of glucose and lipid metabolism, insulin resistance and PPARγ, thereby investigating the potential role for ZIP14 as a biomarker in metabolic diseases
Anthropometric and metabolic data improved after weight loss The obese individuals obtained a weight loss of 12.5 ± 3.4 kg on average and a significant reduction in body mass index (BMI) from 37 ± 3 kg/m2 to 33 ± 3 kg/m2

Summary

Introduction

The expansion and function of adipose tissue are important during the development of insulin resistance and inflammation in obesity. Zinc influx transporter ZIP14, affects proliferation and glucose metabolism but the role of ZIP14 in adipose tissue is still unknown. In addition to obesity-induced inflammation and insulin resistance, obese individuals have an altered zinc homeostasis and reduced levels of circulating zinc [2]. Low dietary zinc intake relates to a disturbed lipid profile, a pronounced inflammatory response, and increased insulin production [4]. Intracellular zinc homeostasis is important for adipose tissue function. Intracellular zinc has been shown to stimulate the insulin signaling pathway, leading to increased glucose uptake, enhanced lipogenesis and reduced production of free fatty acids [5]

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