Ketogenic Diet and Hepatic Ischaemia–Reperfusion Injury: Aggravation or Mitigation?

We are delighted to see this paper titled 'FGF21 protects against ischemia-reperfusion injury in normal and fatty livers'. The study by Ma et al. [1] was the first to investigate the mechanism of action of FGF21 in ischaemia–reperfusion injury (IRI) in normal and fatty livers. It was also found that the ketogenic diet (KD) increased the expression of FGF21 while increasing the degree of hepatic apoptosis. However, the KD on hepatic IRI is still unclear. Xu et al. [2] found that 4-week KD inhibited mitochondrial synthesis, promoted apoptosis and exacerbated myocardial injury in the rat myocardium. Al-Zaid et al. [3] found that 19 weeks of KD in myocardium-injured rats reduced myocardial injury. Therefore, we hypothesised that liver IRI is associated with the feeding time point of KD. The relationship between the KD and fatty liver is controversial; You et al. [4] found that a 2-week KD reduced NAFLD by a mechanism related to the activation of metallothionein-2 (MT2), and Garbow et al. [5] found that hepatic steatosis was present in KD-fed mice within 3 weeks. Therefore, the KD may affect fatty liver IRI through other mechanisms. The mechanism of action of a KD on fatty liver IRI deserves further investigation. Finally, we are very grateful to the authors for this article, which is essential for understanding the mechanism of hepatic IRI. The authors have nothing to report. The authors have nothing to report. The authors declare no conflicts of interest.