Hypothalamic P62 (SQSTM1) regulates energy balance by modulating leptin signaling.

ABSTRACT:

Rationale

The multifaceted functions of p62 (SQSTM1) are increasingly recognized, but its role in hypothalamic metabolism-associated neurons for energy balance has yet to be elucidated.

Methods

Single-nucleus RNA sequencing (snRNA-Seq) was performed on hypothalamic tissues from db/db and db/m mice to explore p62 expression. Overexpression and knockout of p62 in hypothalamic POMC neurons were performed via AAV-mediated gene delivery and Cre-loxP systems. Metabolic outcomes were assessed under normal chow (NCD) and high-fat diet (HFD) conditions. The co-immunoprecipitation and luciferase reporter assays were used to investigate the interaction between p62 and STAT3.

Results

The snRNA-Seq analysis found that p62 was ubiquitously expressed in hypothalamic neurons,

SUBMITTER: Yang S 

PROVIDER: S-EPMC11519807 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature