A 'blob' that runs the body

crucial organ Scientists hope that the new insights into liver development and performance will yield novel therapies for the more than 100 disorders

A 'blob' that runs the body

To the Mesopotamians, the liver was the body’s premier organ, the seat of the human soul and emotions. The ancient Greeks linked the liver to pleasure: The words hepatic and hedonic are thought to share the same root. The Elizabethans referred to their monarch not as the head of state but as its liver, and woe to any people saddled with a lily-livered leader, whose bloodless cowardice would surely prove their undoing. Yet even the most ardent liverati of history may have underestimated the scope and complexity of the organ.

After all, a healthy liver is the one organ in the adult body that, if chopped down to a fraction of its initial size, will rapidly regenerate and perform as if brand-new. Which is a lucky thing, for the liver’s to-do list is second only to that of the brain and numbers well over 300 items. “We have mechanical ventilators to breathe for you if your lungs fail, dialysis machines if your kidneys fail, and the heart is mostly just a pump, so we have an artificial heart,” said Dr Anna Lok, president of the American Association for the Study of Liver Diseases. “But if your liver fails, there’s no machine to replace all its different functions, and the best you can hope for is a transplant.”

Master sampler
And while scientists admit it hardly seems possible, the closer they look, the longer the liver’s inventory of talents and tasks becomes. In one recent study, researchers were astonished to discover that the liver grows and shrinks by up to 40% every 24 hours, while the organs around it barely budge. Others have found that signals from the liver may help dictate our dietary choices, particularly our cravings for sweets. Scientists have also discovered that hepatocytes, the metabolically active cells that constitute 80% of the liver, possess traits not seen in any other normal cells of the body.

Scientists hope that the new insights into liver development and performance will yield novel therapies for the more than 100 disorders that afflict the organ, many of which are on the rise worldwide, in concert with soaring rates of obesity and diabetes. “It’s a funny thing,” said Valerie Gouon-Evans, a liver specialist at the Mount Sinai School of Medicine. “The liver is not a very sexy organ. It doesn’t look important. It just looks like a big blob. But it is quietly vital, the control tower of the body.”

The liver is our largest internal organ, weighing 3.5 pounds and measuring six inches long. The reddish-brown mass of four unevenly sized lobes sprawls like a beached sea lion across the upper right side of the abdominal cavity, beneath the diaphragm and atop the stomach. The organ is always flush with blood, holding about 13% of the body’s supply at any given time. Many of the liver’s unusual features are linked to its intimate association with blood. During fetal development, blood cells are born in the liver, and though that task later migrates to the bone marrow, the liver never loses its taste for the bodywide biochemical gossip that only the circulatory system can bring.

Most organs have a single source of blood. The liver alone has two blood supplies, the hepatic artery conveying oxygen-rich blood from the heart and the hepatic portal vein dropping off blood drained from the intestines and spleen.

As the master sampler of circulating blood, the liver keeps track of the body’s moment-to-moment energy demands, releasing glucose as needed from its stash of stored glycogen, along with any vitamins, minerals, lipids, amino acids or other micronutrients that might be required. New research suggests the liver may take a proactive, as well as a reactive, role in the control of appetite and food choice. “It makes sense that the liver could be a nexus of metabolic control,” said Matthew Gillum of the University of Copenhagen, Denmark. “At some level it knows more than the brain does about energy availability.”

Tracks time
The liver also keeps track of time. In a recent issue of the journal Cell, Ulrich Schibler of the University of Geneva and his colleagues described their studies of the oscillating liver, and how it swells and shrinks each day, depending on an animal’s normal circadian rhythms and feeding schedule. The researchers found that in mice, which normally eat at night and sleep during the day, the size of the liver expands by nearly half after dark and then retrenches come daylight.

The scientists also determined the cause of the changing dimensions. “We wanted to know, is it just extra water or glycogen?” Ulrich said. “Because that would be boring.” It was not boring. “The total gemish, the total soup of the liver turns out to be different,” he said. Protein production in mouse hepatocytes rises sharply at night, followed by equivalent protein destruction during the day.

Evidence suggests that a similar extravaganza of protein creation and destruction occurs in the human liver, too, but the timing is flipped to match our largely diurnal pattern.

The researchers do not yet know why the liver oscillates, but Ulrich suggested it is part of the organ’s fastidious maintenance programme. “The liver gets a lot of bad stuff coming through,” he said. “If you damage some of its components, you need to replace them.” By having a rhythm to that replacement, he said, “you keep the liver in a good state.”


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