Circadian Deregulation: Back Facing the Sun Toward Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) Development

Abstract

Earth’s rotation around its axis has pressured its inhabitants to adapt to 24 h cycles of day and night. Humans adapted their own circadian rhythms to the Earth’s rhythms with a light-aligned awake–sleep cycle. As a consequence, metabolism undergoes drastic changes throughout the circadian cycle and needs plasticity to cope with opposing conditions in the day (when there is an increase in energy demands and food availability), and during the night (when prolonged fasting couples with cyclic changes in the energy demands across the sleep stages). In the last century, human behavior changed dramatically with a disregard for the natural circadian cycles. This misalignment in sleep and eating schedules strongly modulates the metabolism and energy homeostasis, favoring the development of obesity, metabolic syndrome, and metabolic dysfunction-associated steatotic liver disease (MASLD). This review summarizes the effects of circadian disruption, with a particular focus on the feeding and sleep cycles in the development of MASLD and hepatocellular carcinoma.