Mechanisms of hepatic fatty acid oxidation and ketogenesis during fasting

Fasting is part of many weight management and health-boosting regimens. Fasting causes substantial metabolic adaptations in the liver that include the stimulation of fatty acid oxidation and ketogenesis. The induction of fatty acid oxidation and ketogenesis during fasting is mainly driven by interrelated changes in plasma levels of various hormones and an increase in plasma nonesterified fatty acid (NEFA) levels and is mediated transcriptionally by the peroxisome proliferator-activated receptor (PPAR)α, supported by CREB3L3 (cyclic AMP-responsive element-binding protein 3 like 3). Compared with men, women exhibit higher ketone levels during fasting, likely due to higher NEFA availability, suggesting that the metabolic response to fasting shows sexual dimorphism. Here, we synthesize the current molecular knowledge on the impact of fasting on hepatic fatty acid oxidation and ketogenesis.