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Differential effect of Se on insulin resistance: regulation of adipogenesis and lipolysis

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Abstract

Insulin resistance is the characteristic of type 2 diabetes mellitus and metabolic disorder. The biological effect of selenium (Se) on insulin sensitivity and metabolic function was contradictory. In this study, we designed two animal protocols to investigate the effect of physiological Se on high-fat (HF) diet-induced insulin resistance in mice and examined the influence of Se on adipocyte differentiation and lipolysis in isolated bone marrow stromal stem cells. The results showed that pre-treatment with Se, mimicking thiazolidinediones, increased adipocyte differentiation and fat deposit in adipose tissue and reduced ectopic lipid content and consequent ROS generation and mitochondrial dysfunction in livers, protecting against HF diet-induced insulin resistance. Post-treatment with Se promoted lipolysis in adipose tissue and ectopic lipid accumulation in livers and aggravated subsequent ROS generation and mitochondrial dysfunction, exacerbating insulin resistance induced by HF diet. Activation of GPx1 and Sepp1 was responsible for Se-exhibited bi-directional significance, which was at the crossroad of the biological effect of Se, leading to differential directions: one way is to accelerate mitotic clonal expansion and increase key regulators of adipocyte differentiation, such as PPARγ and C/EBPα/β, leading to enhancement of adipogenic differentiation; the other way is to activate PKA/HSL pathway, reinforcing lipolysis. Further studies are needed to elucidate the mechanism underlying GPx1 and Sepp1-exerted differential effects under different conditions. Anyhow, these findings may partly explain the contradiction of the biological significance of Se and demonstrate a novel understanding of the mechanism of Se-exerted benefit or harmful effects in the context of high consumption of fat.

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Abbreviations

BMSCs:

Bone marrow stromal cells

C/EBPα:

CCAAT enhancer binding protein α

C/EBPβ:

CCAAT enhancer binding protein β

FAO:

Fatty acid oxidation

FFA:

Free fatty acids

GPx1:

Glutathione peroxidase 1

HF:

High fat

HSL:

Hormone sensitive lipase

MCE:

Mitotic clonal expansion

MMP:

Mitochondrial membrane potential

MSA:

Mercaptosuccinic acid

mtDNA:

Mitochondrial DNA

OXPHOS:

Mitochondrial oxidative phosphorylation

PPARγ:

Peroxisome proliferator activated receptor γ

ROS:

Reactive oxygen species

Se:

Selenium

Sepp1:

Selenoprotein 1

T2DM:

Type 2 diabetes mellitus

TEM:

Transmission electron microscopy

TCA:

Trichloroacetic acid

TG:

Triglyceride

TZDs:

Thiazolidinediones

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Acknowledgments

This work was supported by National Natural Science Foundation of China (No. 31400724) and Natural Science Foundation of Shaanxi Province (2014JQ4135).

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Authors and Affiliations

  1. Department of Toxicology, Shaanxi Key Lab of Free Radical Biology and Medicine, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Changle West Road 169, Xi’an, 710032, China

    Xin Wang, Hao Wu, Jiangzheng Liu, Ying Liu & Chunxu Hai

  2. The First Brigade of Student, Fourth Military Medical University, Xi’an, 710032, Shaanxi, China

    Zi Long & Quangui Sun

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  1. Xin Wang
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  2. Hao Wu
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  7. Chunxu Hai
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Correspondence to Xin Wang or Chunxu Hai.

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Xin Wang and Hao Wu are coauthors.

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Wang, X., Wu, H., Long, Z. et al. Differential effect of Se on insulin resistance: regulation of adipogenesis and lipolysis. Mol Cell Biochem 415, 89–102 (2016). https://doi.org/10.1007/s11010-016-2679-0

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