Liver Physiology and Energy Metabolism

Hepatic parenchymal cells (hepatocytes and cholangiocytes) and nonparenchymal cells (hepatic sinusoidal endothelial cells, stellate cells, Kupffer cells, and pit cells) have distinct functions that are integrated through extensive cross-talk. Liver parenchymal cells are highly polarized. The distinctive polarization pattern of hepatocytes is unique among glandular epithelial cells. Maintenance of hepatocyte polarization requires energy-consuming processes and is key to the wide array of liver functions. Hepatocytes are organized into functional zones: zone 1 (periportal), zone 2 (midzonal), and zone 3 (pericentral). Gene expression and differential function of hepatocytes in the different zones appear to be regulated by a gradient of cell signaling molecules. Although adult hepatocytes are normally relatively quiescent, they retain a lifelong capacity for massive regeneration following liver injury or loss of volume. The critical role of bile acid signaling as a part of the bile acid-farnesoid X receptor-fibroblast growth factor axis in liver regeneration, and eventual cessation of proliferation when a body weight-appropriate liver mass is achieved, is being revealed. In addition to its synthetic and secretory functions, the liver plays a central role in energy metabolism of the body by orchestrating the synthesis, utilization, and catabolism of carbohydrates, proteins, and lipids. The liver’s molecular “clock” synchronizes the body’s energy needs to the availability of nutrients.