2005). As in genetic models of type‐2 diabetes (ob/ob and db/db mice), PPARα activation and related changes in expression levels of PPARα targets such as PDK4 or MCAD appear only after 5 weeks (Buchanan et al. 2005; Wright et al. 2009). Hence, the molecular changes observed in hearts from rats fed fructose‐enriched water for 6 weeks suggest that the initial stage of “feedforward” activation of β‐oxidation has been replaced by a chronic PPARα‐driven increase in flux through this pathway. Here, PDK4 is linked to medium chain acyl-CoA dehydrogenase deficiency.