MCD enzyme deficiency drives early mortality and multiorgan metabolic disruption in Dahl salt-sensitive rats.

ABSTRACT: Malonyl-CoA decarboxylase (MCD), encoded by Mlycd, plays a critical role in regulating malonyl-CoA levels, fatty acid oxidation, and glucose metabolism. To investigate the systemic effects of Mlycd deficiency, we generated a genetically modified rat model with partial loss of Mlycd. Due to high preweaning mortality in homozygous mutants, we focused on heterozygous and wild-type animals for cross-tissue targeted proteomic and metabolomic analyses. Alterations in metabolic and stress-related pathways were observed across the heart, kidney, liver, plasma, and urine. Enrichment of oxidative phosphorylation, fatty acid metabolism, immune responses, and autophagy-related signaling was noted. Elevated levels of oxidative stress-related proteins and disrupted autophagy regulat

SUBMITTER: Kravtsova O 

PROVIDER: S-EPMC12808911 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature