Proteasome dysfunction disrupts adipogenesis and induces inflammation via ATF3.

ABSTRACT:

Objective

Regulation of proteasomal activity is an essential component of cellular proteostasis and function. This is evident in patients with mutations in proteasome subunits and associated regulators, who suffer from proteasome-associated autoinflammatory syndromes (PRAAS). These patients display lipodystrophy and fevers, which may be partly related to adipocyte malfunction and abnormal thermogenesis in adipose tissue. However, the cell-intrinsic pathways that could underlie these symptoms are unclear. Here, we investigate the impact of two proteasome subunits implicated in PRAAS, Psmb4 and Psmb8, on differentiation, function and proteostasis of brown adipocytes.

Methods

In immortalized mouse brown pre-adipocytes, levels of Psmb4, Psmb8, and downstream effectors genes were

SUBMITTER: Willemsen N 

PROVIDER: S-EPMC9194453 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature