PMID- 38496622
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240318
DP  - 2024 Mar 6
TI  - Cell-state dependent regulation of PPAR (gamma) signaling by ZBTB9 in adipocytes.
LID - 2024.03.04.583402 [pii]
LID - 10.1101/2024.03.04.583402 [doi]
AB  - Adipocytes play a critical role in metabolic homeostasis. Peroxisome 
      proliferator-activated receptor- (gamma) (PPAR (gamma) ) is a nuclear hormone receptor 
      that is a master regulator of adipocyte differentiation and function. ZBTB9 was 
      predicted to interact with PPAR (gamma) based on large-scale protein interaction 
      experiments. In addition, GWAS studies in the type 2 diabetes (T2D) Knowledge 
      Portal revealed associations between Z btb9 and both BMI and T2D risk. Here we 
      show that ZBTB9 positively regulates PPAR (gamma) activity in mature adipocytes. 
      Surprisingly Z btb9 knockdown (KD) also increased adipogenesis in 3T3-L1 cells 
      and human preadipocytes. E2F activity was increased and E2F downstream target 
      genes were upregulated in Zbtb9 -KD preadipocytes. Accordingly, RB 
      phosphorylation, which regulates E2F activity, was enhanced in Zbtb9 -KD 
      preadipocytes. Critically, an E2F1 inhibitor blocked the effects of Zbtb9 
      deficiency on adipogenic gene expression and lipid accumulation. Collectively, 
      these results demonstrate that Zbtb9 inhibits adipogenesis as a negative 
      regulator of Pparg expression via altered RB-E2F1 signaling. Our findings reveal 
      complex cell-state dependent roles of ZBTB9 in adipocytes, identifying a new 
      molecule that regulates adipogenesis and adipocyte biology as both a positive and 
      negative regulator of PPAR (gamma) signaling depending on the cellular context, and 
      thus may be important in the pathogenesis and treatment of obesity and T2D.
FAU - Xu, Xuan
AU  - Xu X
FAU - Charrier, Alyssa
AU  - Charrier A
FAU - Congrove, Sunny
AU  - Congrove S
FAU - Buchner, David A
AU  - Buchner DA
AUID- ORCID: 0000-0003-3920-4871
LA  - eng
PT  - Preprint
DEP - 20240306
PL  - United States
TA  - bioRxiv
JT  - bioRxiv : the preprint server for biology
JID - 101680187
PMC - PMC10942320
EDAT- 2024/03/18 06:43
MHDA- 2024/03/18 06:44
PMCR- 2024/03/15
CRDT- 2024/03/18 04:40
PHST- 2024/03/18 06:44 [medline]
PHST- 2024/03/18 06:43 [pubmed]
PHST- 2024/03/18 04:40 [entrez]
PHST- 2024/03/15 00:00 [pmc-release]
AID - 2024.03.04.583402 [pii]
AID - 10.1101/2024.03.04.583402 [doi]
PST - epublish
SO  - bioRxiv [Preprint]. 2024 Mar 6:2024.03.04.583402. doi: 10.1101/2024.03.04.583402.