At the Crossroads of Health and Disease: Consequences of Fat in the Liver

The liver plays a central role in regulating lipid and glucose metabolism, particularly in transitioning between energy storage and provision in fed and fasting states. Loss of metabolic flexibility, characterized by the impaired capacity to shift between different energy substrates, sets the stage for accumulation of hepatic triglyceride as lipid droplets and further metabolic perturbations. Cross talk between the liver and other organs, including adipose tissue, pancreas, and muscle, is relevant in this transition. In addition to the metabolic consequences of steatosis, there are significant liver risks related to triggered inflammatory and fibrotic processes. Steatotic liver diseases affect an estimated one in three adults globally and contribute to substantial morbidity and mortality. This review focuses on the liver's role in lipid metabolism, defining metabolic health and unhealth, the pathogenic underpinnings that lead to steatohepatitis and hepatic fibrosis, and the clinical features and therapies for the most common forms of steatotic liver diseases.