FTO inhibition mitigates high-fat diet-induced metabolic disturbances and cognitive decline in SAMP8 mice.

ABSTRACT: This study investigated the effects of fat mass and obesity-associated (FTO) inhibition on cognitive function and metabolic parameters of senescence-accelerated mouse prone 8 (SAMP8) mice fed a high-fat diet (HFD). SAMP8 mice fed an HFD exhibited increased body weight, impaired glucose tolerance, and elevated serum leptin levels. In epididymal white adipose tissue (eWAT), pharmacological treatment with FB23, a well-established FTO inhibitor, increased leptin production and modulated genes involved in lipid metabolism (Cpt1a, Atgl, Hsl, Fas), oxidative stress (OS) (Bip, Edem), and inflammation (Mcp1, Tnfα). Expression of hepatic genes related to lipid metabolism (Cpt1a, Atgl, Mgl, Dgat2, Srebp, Plin2) and OS (catalase, Edem) were modulated by FB23, although hepatic steatosis remained unchan

SUBMITTER: Irisarri A 

PROVIDER: S-EPMC11843768 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature