Molecular and Cellular Biochemistry

, Volume 415, Issue 1–2, pp 89–102 | Cite as

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

Article

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.

Keywords

Selenium Insulin resistance High-fat diet Adipocyte differentiation Lipolysis 

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

Supplementary material

11010_2016_2679_MOESM1_ESM.docx (93 kb)
Supplementary material 1 (DOCX 93 kb)

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 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 HealthFourth Military Medical UniversityXi’anChina
  2. 2.The First Brigade of StudentFourth Military Medical UniversityXi’anChina

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