NIH R01 · 2025
Determining the Biological Effects of Mitochondrial Acyl Toxicity
PROJECT SUMMARY During acute metabolic stress and chronic metabolic disease, such as obesity and diabetes, the accumulation of fatty acid oxidation intermediary metabolites has long been suspected of toxicity. Among these possible lipotoxic metabolites are long-chain acylcarnitines (LCACs), which purportedly interfere with critical physiological processes including insulin signaling, calcium homeostasis, and mitochondrial function. However, mechanistically linking defects in these processes to LCAC accumulation has been difficult due to a lack of LCAC-accumulating pre-clinical models. We overcame this barrier by developing a unique mouse model of LCAC accumulation by deleting the enzyme…
From the public funding record at NIH RePORTER. Describes the funded project, not the reviews below.