The transcriptional regulator Zfat is essential for maintenance and differentiation of the adipocytes

Abstract

Adipocytes play crucial roles in the control of whole‐body energy homeostasis. Differentiation and functions of the adipocytes are regulated by various transcription factors. Zfat (zinc‐finger protein with AT‐hook) is a transcriptional regulator that controls messenger RNA expression of specific genes through binding to their transcription start sites. Here we report important roles of Zfat in the adipocytes. We establish inducible Zfat‐knockout (Zfat iKO) mice where treatment with tamoxifen causes a marked reduction in Zfat expression in various tissues. Tamoxifen treatment of Zfat iKO mice reduces the white adipose tissues (WATs) mass, accompanied by the decreased triglyceride levels. Zfat is expressed in both the adipose‐derived stem cells (ADSCs) and mature adipocytes in the WATs. In ex vivo assays of the mature adipocytes differentiated from the Zfat iKO ADSCs, loss of Zfat in the mature adipocytes reduces the triglyceride levels, suggesting cell autonomous roles of Zfat in the maintenance of the mature adipocytes. Furthermore, we identify the Atg13, Brf1, Psmc3, and Timm22 genes as Zfat‐target genes in the mature adipocytes. In contrast, loss of Zfat in the ADSCs impairs adipocyte differentiation with the decreased expression of C/EBPα and adiponectin. Thus, we propose that Zfat plays crucial roles in maintenance and differentiation of the adipocytes.

Identification of a Candidate Gene Regulating Intramuscular Fat Content in Pigs through the Integrative Analysis of Transcriptomics and Proteomics Data

“…The reduced expression of PSMC3 may contribute to the observed decrease in C/EBPα expression and TG levels in ZFAT-depleted adipocytes. 23 Significantly, the expression trends of COL5A2 and PSMC3 in the IMF-H and IMF-L groups observed in the present study are consistent with the aforementioned observations.…”

CENP-B promotes the centromeric localization of ZFAT to control transcription of noncoding RNA

“…The immunoblotting procedure was performed as previously described (19,37,42) using antibodies detailed in the Supplemental Table S3. Co-immunoprecipitation (Co-IP) was performed as previously described (43).…”

“…The ZFAT genes have been identified in vertebrates with highly conserved amino acid sequences ( 14 ), suggesting their crucial role in physiological processes. Indeed, we have previously demonstrated that ZFAT is essential for embryonic development ( 15 ) and the homeostasis of T cells ( 16 , 17 , 18 ) and adipocytes ( 19 ). Recently, we reported that ZFAT plays an important role in the centromeric ncRNA transcription in human cells ( 20 ).…”

miR-383-5p Regulates Preadipocyte Proliferation and Differentiation by Targeting RAD51AP1

“…However, there is limited research on the regulation of adipogenesis by RAD51AP1 . Among this research, RAD51AP1 was found in prenatal testosterone-induced visceral adipose tissue of female sheep and was highly expressed in the adipose-derived stem cells, which may be involved in lipid metabolism processes [ 48 , 49 ]. In our research, RAD51AP1 was a direct miR-383-5p target.…”