Human genetics identify convergent signals in mitochondrial LACTB-mediated lipid metabolism in cardiovascular-kidney-metabolic syndrome.

ABSTRACT: The understanding of cardiovascular-kidney-metabolic syndrome remains difficult despite recently performed large scale genome-wide association studies. Here, we identified beta-lactamase (LACTB), a novel gene whose expression is targeted by genetic variations causing kidney dysfunction and hyperlipidemia. Mice with LACTB deletion developed impaired glucose tolerance, elevated lipid levels, and increased sensitivity to kidney disease, while mice with tubule-specific overexpression of LACTB were protected from kidney injury. We show that LACTB is a novel mitochondrial protease cleaving and activating phospholipase A2 group VI (PLA2G6), a kidney-metabolic risk gene itself. Genetic deletion of PLA2G6 in tubule-specific LACTB-overexpressing mice abolished the protective function of LACTB. Via m

SUBMITTER: Li S 

PROVIDER: S-EPMC11972450 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature