Abstract
Understanding the molecular mechanisms that drive adipogenesis is important in developing new treatments for obesity and diabetes. Epigenetic regulations determine the capacity of adipogenesis. In this study, we examined the role of a histone H3 lysine 27 demethylase, the ubiquitously transcribed tetratricopeptide repeat protein on the X chromosome (Utx), in the differentiation of mouse embryonic stem cells (mESCs) to adipocytes. Using gene trapping, we examined Utx-deficient male mESCs to determine whether loss of Utx would enhance or inhibit the differentiation of mESCs to adipocytes. Utx-deficient mESCs showed diminished potential to differentiate to adipocytes compared to that of controls. In contrast, Utx-deficient preadipocytes showed enhanced differentiation to adipocytes. Microarray analyses indicated that the β-catenin/c-Myc signaling pathway was differentially regulated in Utx-deficient cells during adipocyte differentiation. Therefore, our data suggest that Utx governs adipogenesis by regulating c-Myc in a differentiation stage-specific manner and that targeting the Utx signaling pathway could be beneficial for the treatment of obesity, diabetes, and congenital utx-deficiency disorders.
Highlights
Obesity is a major health concern worldwide [1,2,3]
To examine whether Utx is involved in adipogenesis, we generated Utx-deficient mouse embryonic stem cells (mESCs) (Fig 1A)
Utx-null female mESCs are unable to differentiate into mesoderm and Utx-null female embryos arrest at E10.5 [16,19]
Summary
Obesity is a major health concern worldwide [1,2,3]. Overconsumption of energy-rich foods facilitates fat deposition in adipose tissue [4]. Adipose tissue has a significant buffering capacity that permits it to adapt to excessive energy intake by changing the number and size of adipocytes [5,6]. The pathological accumulation of fat in the body leads to the risk of developing obesity-associated metabolic disorders [4,7]. Multiple processes of adipocyte differentiation including commitment to mesoderm, preadipocytes, and terminal differentiation into adipocytes are involved during adipocyte differentiation [8]. The mechanism of stage-specific regulation of adipogenesis is not still fully understood
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