JAK-STAT pathway activation compromises nephrocyte function in a <i>Drosophila</i> high-fat diet model of chronic kidney disease.

ABSTRACT: Chronic kidney disease is a major health issue and is gaining prevalence. Using a Drosophila model for chronic kidney disease, we show that a high-fat diet (HFD) disrupts the slit diaphragm filtration structure in nephrocytes, the fly functional equivalent of mammalian podocytes. The structural disruption resulted in reduced filtration function in the affected nephrocytes. We demonstrate that HFD activates the JAK-STAT pathway in nephrocytes, which has previously been linked to diabetic kidney disease. JAK-STAT activation was initiated by increased expression and release of the adipokine, Upd2, from the fat body. This leptin-like hormone is a known ligand of JAK-STAT. Both genetic and pharmacological inhibition of JAK-STAT restored nephrocyte HFD-associated dysfunction. Altogether,

SUBMITTER: Zhao Y 

PROVIDER: S-EPMC12755883 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature