Regulation of human subcutaneous adipocyte differentiation by EID1

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.

Transcriptional analysis of adipose tissue during development reveals depot-specific responsiveness to maternal dietary supplementation

“…The expression of mRNA is regulated by a balance between transcription and mRNA degradation, and the C1.2 module captures this complexity in the control of UCP1 37 . We found transcription factors that stimulate a cell’s transition from myoblastic precursors to brown fat cells, including C/EBPβ and EP300 22 , 38 . Other members of this module were EIF4B, EIF4G3, EIF3D and EIF3G, known transcriptional factors that downregulate mRNA transcription of UCP1 in response to raised temperature 39 .…”

The Beige Adipocyte as a Therapy for Metabolic Diseases

“…In addition, a blockage of pRb activity can control the decision of adipocyte precursors to progress toward the development of beige adipocytes. EP300 Interacting Inhibitor of Differentiation 1 (EID1/CR1) can reduce the activity of pRb and induce differentiation to beige adipocytes [110,111]. p107, a cell-cycle regulator that belongs to the pRb family, has demonstrated an important role in the decision of mesenchymal stem cells in the differentiation of beige adipocytes [112] Figure 1.…”

Epigenética en el origen de la obesidad: perspectiva desde la célula grasa

“…Los adipocitos blancos son células generalmente redondas, grandes, con un diámetro que varía de 25 a 200 mm, que contienen una gran gota de triglicéridos, rodeada por una fina capa de citoplasma con pocas mitocondrias, y un núcleo aplanado situado en la periferia (21) (figura 2).…”