Ceramide homeostasis in hepatic lipid droplets

Almost all eukaryotic cells have the capacity to form lipid droplets (LDs) in conditions of excess energy. Traditionally thought to be just inert fat reservoirs, LDs have recently emerged as important metabolic regulators of cellular stress response that buffer excess free fats and protect cells from lipotoxicity. Ceramide is a bioactive lipid that accumulates in metabolic tissues during fat oversupply. Emerging evidence suggests that sphingolipids and sphingolipid-metabolizing enzymes are found in the LDs and affect LD biogenesis and functions. This article aims to summarize the evidence, delineate some plausible functions of ceramide in hepatic LD biogenesis, and illustrate some of the challenges in this novel field of research. We focus on the biogenesis of LDs in hepatocytes, the parenchymal cells of the liver, because non-alcoholic fatty liver disease is the quintessential manifestation of metabolic stress caused by fat oversupply.