Regulation of human subcutaneous adipocyte differentiation by EID1 Diana Vargas 1 , Noriaki Shimokawa 2 , Ryosuke Kaneko 3 , Wendy Rosales 1 , Adriana Parra 1 ,A ´ ngela Castellanos 1 , Noriyuki Koibuchi 2 and Fernando Lizcano 1 1 Center of Biomedical Research (CIBUS), Universidad de La Sabana, Km. 7 Autopista Norte de Bogota, 140013 Chia, Colombia 2 Department of Integrative Physiology, Gunma University, Maebashi, Japan 3 Institute of Experimental Animal Research, Gunma University, Maebashi, Japan Correspondence should be addressed to F Lizcano Email fernando.lizcano@ unisabana.edu.co Abstract Increasing thermogenesis in white adipose tissues can be used to treat individuals at high risk for obesity and cardiovascular disease. The objective of this study was to determine the function of EP300-interacting inhibitor of differentiation (EID1), an inhibitor of muscle differentiation, in the induction of beige adipocytes from adipose mesenchymal stem cells (ADMSCs). Subcutaneous adipose tissue was obtained from healthy women undergoing abdominoplasty. ADMSCs were isolated in vitro, grown, and transfected with EID1 or EID1 siRNA, and differentiation was induced after 48 h by administering rosiglitazone. The effects of EID1 expression under the control of the aP2 promoter (aP2-EID1) were also evaluated in mature adipocytes that were differentiated from ADMSCs. Transfection of EID1 into ADMSCs reduced triglyceride accumulation while increasing levels of thermogenic proteins, such as PGC1a, TFAM, and mitochondrial uncoupling protein 1 (UCP1), all of which are markers of energy expenditure and mitochondrial activity. Furthermore, increased expression of the beige phenotype markers CITED1 and CD137 was observed. Transfection of aP2-EID1 transfection induced the conversion of mature white adipocytes to beige adipocytes, as evidenced by increased expression of PGC1a, UCP1, TFAM, and CITED1. These results indicate that EID1 can modulate ADMSCs, inducing a brown/beige lineage. EID1 may also activate beiging in white adipocytes obtained from subcutaneous human adipose tissue. Key Words " retinoblastoma " ADMSCs " PPARg " EID1 " beige fat Journal of Molecular Endocrinology (2016) 56, 113–122 Introduction Obesity and its associated metabolic diseases, such as type 2 diabetes mellitus, hypertension, and cardiovascular disease, are increasing in prevalence due to a combination of environmental factors and genetic variations (van Dijk et al. 2014, Robbins et al. 2014). Recent research has led to a deeper understanding of adipocyte physiology. These advances may provide important clues to find effective options for treating obesity (Nedergaard et al. 2011, Wu et al. 2013). Adipocytes develop from adipose mesenchymal stem cells (ADMSCs), which are primarily of mesodermal origin. However, the specific localizations of fat cells and their associated differential gene expression patterns, thermogenic capacities, and abilities to induce vascular complications suggest that they have diverse origins. Indeed, various types of adipocytes were recently identified in adults (Sidossis & Kajimura 2015). In contrast with white adipose tissue (WAT), brown adipose tissue (BAT) is specialized for the dissipation of chemical energy in the form of heat, a process dependent on mitochondrial uncoupling protein 1 (UCP1). Adult humans lack classical BAT but possess a subset of cold-inducible beige adipocytes in their WAT. The recognition of the phenotypic plasticity Journal of Molecular Endocrinology Research D VARGAS and others Effects of EID1 in human adipocytes 56 :2 113–122 http://jme.endocrinology-journals.org Ñ 2016 Society for Endocrinology DOI: 10.1530/JME-15-0148 Printed in Great Britain Published by Bioscientifica Ltd. Downloaded from Bioscientifica.com at 04/09/2023 09:38:21AM via free access