PARIS/ZNF746 DNA-binding domain deficiency promotes adipose tissue hyperplasia and hepatic lipid accumulation.

ABSTRACT: Zinc finger protein 746 (ZNF746), also known as PARKIN-interacting substrate (PARIS), is a KRAB-ZFP family transcriptional repressor implicated in Parkinson's disease and adipogenesis. Its unclear role in systemic metabolism led us to investigate PARIS-mediated metabolic function by generating mice with a knockout of Znf746 exon 7 (P7KO), containing the DNA-binding domain. Under a high-fat diet, P7KO mice exhibited larger gains in body and adipose tissue weight alongside improved insulin sensitivity and reduced adipocyte size compared with wild-type mice, suggesting hyperplastic expansion of white adipose tissue. P7KO mice also showed elevated anti-inflammatory markers in adipose tissues, in contrast to accumulation of lipids and upregulation of lipogenic genes, without changes in glucose

SUBMITTER: Hachiya K 

PROVIDER: S-EPMC12528463 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature