In Vivo Hyperpolarized 13C-MRS Shows Abnormal Cardiac Metabolism in the PPARα Knockout Mouse

Michael Dodd¹, ², Rosalind Bray¹, Vicky Ball¹, Mark Cole¹, Kieran Clarke¹, Damian Tyler¹

Peroxisome proliferator-activated receptor-α (PPARα)plays an important role in the regulation of fatty acid oxidation. The PPARα knockout mouse (PPARα-KO) has been developed to investigate the role of PPARα in cardiac metabolism and disease. This work aimed to assess the in vivo metabolic phenotype of PPARα-KO mice using hyperpolarized ¹³C-MRS. During the fed state, PPARα-KO mice had significantly elevated pyruvate dehydrogenase (PDH) flux compared to controls. During fasting there was a similar reduction in PDH flux in both control and PPARα-KO mice, indicating that this alteration is PPARα independent and is a response to increased fatty acid supply and utilization.