title: Differential effect of Se on insulin resistance: regulation of adipogenesis and lipolysis.
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.
authors.affiliation: 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. xinwang@fmmu.edu.cn.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.affiliation: The First Brigade of Student, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
authors.forename: Zi
authors.initials: Z
authors.lastname: Long
authors.affiliation: The First Brigade of Student, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
authors.forename: Quangui
authors.initials: Q
authors.lastname: Sun
authors.affiliation: 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.
authors.forename: Jiangzheng
authors.initials: J
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: 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. cx-hai@fmmu.edu.cn.
authors.forename: Chunxu
authors.initials: C
authors.lastname: Hai
mesh_terms: D050156:Adipogenesis / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D059305:Diet, High-Fat; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D007333:Insulin Resistance; D008066:Lipolysis / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000502:physiology; D010084:Oxidation-Reduction; D012643:Selenium / Q000502:physiology*
chemical_list: D012643:Selenium
keywords: Adipocyte differentiation; High-fat diet; Insulin resistance; Lipolysis; Selenium