Sex- and Ketogenesis-Dependent Effects of Intermittent Fasting on Diet-Induced Fatty Liver Disease.

We investigated whether ketogenesis is required for the metabolic benefits of intermittent fasting (IF) and whether these effects differ between sexes. We specifically asked whether ketogenesis drives IF-mediated protection against obesity and fatty liver disease in male and female mice. We found that IF reduced adiposity independently of ketogenesis in both sexes, but its antisteatotic and antifibrotic effects were ketogenesis-dependent in male mice and minimal in female mice. These findings reveal a sex-dependent ketogenesis-inflammation-fibrosis axis and highlight the need to consider sex and ketone metabolism when designing dietary or therapeutic interventions.