ZBTB16 Overexpression Enhances White Adipogenesis and Induces Brown-Like Adipocyte Formation of Bovine White Intramuscular Preadipocytes

Wei, Song; Zhang, Mengmeng; Zheng, Yan‐Song; Yan, Peishi

doi:10.1159/000492697

Cited by 46 publications

(24 citation statements)

References 37 publications

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“…In line with the present study, ZBTB16 was identified as a potential early and late-stage differentiation marker during adipogenesis in human adipose-derived stromal cells (Ambele et al, 2016). Wei et al (2018) reported that ZBTB16 overexpression promoted white adipogenesis and induced brown-like adipocyte formation for bovine white intramuscular preadipocytes. Besides, it was reported that zoledronic acid accelerated the MSCs differentiation to the osteoblast cells through promotion of the ZBTB16 expression (Marofi et al, 2019).…”

Section: A a A A A A A A A A A A A A A A A A A A A A A A A A A A A Asupporting

confidence: 90%

Identification of key genes of human bone marrow stromal cells adipogenesis at an early stage

Chen

Song

Wang

et al. 2020

PeerJ

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Background Bone marrow adipocyte (BMA), closely associated with bone degeneration, shares common progenitors with osteoblastic lineage. However, the intrinsic mechanism of cells fate commitment between BMA and osteogenic lineage remains unclear. Methods Gene Expression Omnibus (GEO) dataset GSE107789 publicly available was downloaded and analyzed. Differentially expressed genes (DEGs) were analyzed using GEO2R. Functional and pathway enrichment analyses of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were conducted by The Database for Annotation, Visualization and Integrated Discovery and Gene set enrichment analysis software. Protein–protein interactions (PPI) network was obtained using STRING database, visualized and clustered by Cytoscape software. Transcriptional levels of key genes were verified by real-time quantitative PCR in vitro in Bone marrow stromal cells (BMSCs) undergoing adipogenic differentiation at day 7 and in vivo in ovariectomized mice model. Results A total of 2,869 DEGs, including 1,357 up-regulated and 1,512 down-regulated ones, were screened out from transcriptional profile of human BMSCs undergoing adipogenic induction at day 7 vs. day 0. Functional and pathway enrichment analysis, combined with modules analysis of PPI network, highlighted ACSL1, sphingosine 1-phosphate receptors 3 (S1PR3), ZBTB16 and glypican 3 as key genes up-regulated at the early stage of BMSCs adipogenic differentiation. Furthermore, up-regulated mRNA expression levels of ACSL1, S1PR3 and ZBTB16 were confirmed both in vitro and in vivo. Conclusion ACSL1, S1PR3 and ZBTB16 may play crucial roles in early regulation of BMSCs adipogenic differentiation

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Section: A a A A A A A A A A A A A A A A A A A A A A A A A A A A A Asupporting

confidence: 90%

Identification of key genes of human bone marrow stromal cells adipogenesis at an early stage

Chen

Song

Wang

et al. 2020

PeerJ

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“…The bovine preadipocyte cells were collected from a healthy newborn calve (5‐day old) of the Qinchuan cattle breed, using the previously used method (Meissburger et al, 2016; Wang et al, 2018; Wei, Zhang, Zheng, & Yan, 2018). Back fat tissue from the longissimus dorsi muscle area was extracted under a sterile and hygienic environment.…”

Section: Methodsmentioning

confidence: 99%

Bta‐miR‐149‐5p inhibits proliferation and differentiation of bovine adipocytes through targeting CRTCs at both transcriptional and posttranscriptional levels

Khan

Raza

Junjvlieke

et al. 2020

Journal Cellular Physiology

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MicroRNAs are small, single stranded, and noncoding RNAs that have been proven to be potent regulators of adipogenesis. However, the role of bta‐miR‐149‐5p in regulating bovine adipogenesis is still unclear. Expression profiling in different stages of adipogenesis revealed that bta‐miR‐149‐5p was enriched in the proliferation stage, and also on Day 9 of differentiation in bovine adipocytes. Our gain of function study showed that bta‐miR‐149‐5p can negatively regulate both bovine adipocyte proliferation and differentiation. Overexpression of bta‐miR‐149‐5p suppressed the expression of proliferation marker genes at both the messenger RNA (mRNA) and protein levels, markedly decreased the percentage of S‐phase cells, decreased the number of EdU‐stained cells, and substantially reduced adipocyte proliferation vitality in the cell count assay. Collectively, these findings elucidated that bta‐miR‐149‐5p inhibits adipocyte proliferation. Furthermore, overexpression of bta‐miR‐149‐5p also suppressed the expression of adipogenic genes at both the mRNA and protein levels, inhibited lipid accumulation, and reduced the secretion of adiponectin in bovine adipocytes. Furthermore, a luciferase activity assay explored how bta‐miR‐149‐5p targeted CRTCs (CRTC1 and CRTC2) directly. This targeting was further validated by the mRNA and protein level expression of CRTC1 and CRTC2, which were down regulated by bta‐miR‐149‐5p overexpression. Moreover, bta‐miR‐149‐5p indirectly targeted CRTC1 and CRTC2 through regulating their key transcription factors. Overexpression of bta‐miR‐149‐5p suppressed the expression of SMAD3, while enriched the expression of NRF1, which are the key transcription factors and proven regulators of CRTC1. Overexpression of bta‐miR‐149‐5p also repressed the expression of C/EBPγ, XBP1, INSM1, and ZNF263, which are the key regulators of CRTCs, at both the mRNA and protein levels. These findings suggest that bta‐miR‐149‐5p is a negative regulator of CRTC1 and CRTC2 both at transcriptional and posttranscriptional level. Taken together, these findings suggest that bta‐miR‐149‐5p can regulate adipogenesis, which implies that bta‐miR‐149‐5p could be a target for increasing intramuscular fat in beef cattle.

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“…Bovine preadipocyte cells were collected from a healthy newborn calf (5 days old) of the Qinchuan cattle breed using the methods previously described [76,77,78]. The back-fat tissue from the longissimus dorsi muscle area was extracted under aseptic conditions.…”

Section: Methodsmentioning

confidence: 99%

Function and Transcriptional Regulation of Bovine TORC2 Gene in Adipocytes: Roles of C/EBP, XBP1, INSM1 and ZNF263

Khan

Raza

Junjvlieke

et al. 2019

IJMS

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The TORC2 gene is a member of the transducer of the regulated cyclic adenosine monophosphate (cAMP) response element binding protein gene family, which plays a key role in metabolism and adipogenesis. In the present study, we confirmed the role of TORC2 in bovine preadipocyte proliferation through cell cycle staining flow cytometry, cell counting assay, 5-ethynyl-2′-deoxyuridine staining (EdU), and mRNA and protein expression analysis of proliferation-related marker genes. In addition, Oil red O staining analysis, immunofluorescence of adiponectin, mRNA and protein level expression of lipid related marker genes confirmed the role of TORC2 in the regulation of bovine adipocyte differentiation. Furthermore, the transcription start site and sub-cellular localization of the TORC2 gene was identified in bovine adipocytes. To investigate the underlying regulatory mechanism of the bovine TORC2, we cloned a 1990 bp of the 5’ untranslated region (5′UTR) promoter region into a luciferase reporter vector and seven vector fragments were constructed through serial deletion of the 5′UTR flanking region. The core promoter region of the TORC2 gene was identified at location −314 to −69 bp upstream of the transcription start site. Based on the results of the transcriptional activities of the promoter vector fragments, luciferase activities of mutated fragments and siRNAs interference, four transcription factors (CCAAT/enhancer-binding protein C/BEPγ, X-box binding protein 1 XBP1, Insulinoma-associated 1 INSM1, and Zinc finger protein 263 ZNF263) were identified as the transcriptional regulators of TORC2 gene. These findings were further confirmed through Electrophoretic Mobility Shift Assay (EMSA) within nuclear extracts of bovine adipocytes. Furthermore, we also identified that C/EBPγ, XBP1, INSM1 and ZNF263 regulate TORC2 gene as activators in the promoter region. We can conclude that TORC2 gene is potentially a positive regulator of adipogenesis. These findings will not only provide an insight for the improvement of intramuscular fat in cattle, but will enhance our understanding regarding therapeutic intervention of metabolic syndrome and obesity in public health as well.

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ZBTB16 Overexpression Enhances White Adipogenesis and Induces Brown-Like Adipocyte Formation of Bovine White Intramuscular Preadipocytes

Cited by 46 publications

References 37 publications

Identification of key genes of human bone marrow stromal cells adipogenesis at an early stage

Identification of key genes of human bone marrow stromal cells adipogenesis at an early stage

Bta‐miR‐149‐5p inhibits proliferation and differentiation of bovine adipocytes through targeting CRTCs at both transcriptional and posttranscriptional levels

Function and Transcriptional Regulation of Bovine TORC2 Gene in Adipocytes: Roles of C/EBP, XBP1, INSM1 and ZNF263

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