Microglial progranulin differently regulates hypothalamic lysosomal function in lean and obese conditions via cleavage-dependent mechanisms.

ABSTRACT: Progranulin (PGRN) is a secretory precursor protein composed of 7.5 granulins (GRNs). Mutations in the PGRN-encoding gene Grn have been associated with neurodegenerative diseases. In our previous study, we found that Grn depletion in microglia disrupted glucose metabolism in mice fed a normal chow diet (NCD) but prevented the development of obesity in mice on a high-fat diet (HFD). Given that PGRN regulates lysosomal functions, we investigated lysosomal changes in the hypothalamus of mice with microglia-specific Grn depletion. Here we report that microglia-specific Grn depletion affects the lysosomes of hypothalamic proopiomelanocortin (POMC) neurons and microglia in diet-dependent fashion. Under NCD conditions, microglial Grn depletion led to increased lysosome mass, reduced lysosomal deg

SUBMITTER: Park CB 

PROVIDER: S-EPMC11887206 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature