At the back of a rowing boat sits the coxswain (pronounced “kaak-sn”) or “cox” for short. Unlike the rest of the muscle-bound rowing crew, the cox is much smaller and does not actually row. You might wonder: Why they should be kept in the boat if they don’t help with the energy-demanding tasks?
From the back of the boat, and facing forward, the cox is ideally positioned to steer the boat and direct the team members to help keep the crew and strokes synchronized. The rowers face backward, allowing them to propel the boat forward when they pull on the oars. The position the team members hold in the boat dictate their roles, and the rowers and the cox perform very different, but equally important, functions. This division of tasks based on their location optimizes the team’s performance.
A similar situation happens on a much smaller scale in the liver, which is made up of thousands of hexagonal units called lobules. Blood that’s rich in oxygen, nutrients and hormones flows from the corners of the lobules to its center. As the blood travels along the lobules, liver cells take and use these nutrients, which creates a slope or gradient formation.
Just like the rowing crew, the position of the liver cells within the lobule dictates their role. Cells at the edges of the lobule are exposed to much more oxygen and nutrients from the blood, so they do much more energy-demanding work, such as making glucose. Cells at the center of the lobule perform less energy-demanding jobs, such as breaking down glucose, because they have less oxygen and nutrients available to them.
Dividing these tasks within the lobule—called liver zonation—is based on the liver cells’ position along the lobule and other factors. This ability to separate processes in the liver is vital for the organ to function most efficiently.
Just like losing either the cox or the rowers from the boat would be disastrous for a crew’s performance, disruption of liver zonation can be harmful, too. When liver zonation is disrupted in people with nonalcoholic fatty liver disease and liver cancer, it can contribute to disease progression. Despite liver zonation being identified over a century ago, it’s only recently that new technologies have let scientists study it in the intact liver. Learning how and why the liver separates important processes to operate efficiently will help researchers understand what causes liver disease and how to steer the boat toward better therapies.
Rory Cunningham, PhD, is a postdoctoral research fellow at the National Cancer Institute. His research focuses on metabolic perturbations on the liver such as diet, fasting and exercise, to investigate hepatic mitochondrial dynamics.