The Liver: 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. Its powers are so profound that the old toss-away line, “What am I, chopped liver?” can be seen as a kind of humblebrag.
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, including systematically reworking the food we eat into usable building blocks for our cells; neutralizing the many potentially harmful substances that we incidentally or deliberately ingest; generating a vast pharmacopoeia of hormones, enzymes, clotting factors and immune molecules; controlling blood chemistry; and really, we are just getting started.
“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 and director of clinical hepatology at the University of Michigan.
美国肝病研究协会(American Association for the Study of Liver Diseases)会长、密歇根大学肝病研究与临床肝病学主任安娜·洛克(Anna Lok)博士说：“如果你的肺部有问题，我们有呼吸机帮你呼吸；如果你的肾脏有问题，我们有透析机；心脏主要就是一个泵，所以可以使用人造心脏。”
“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.”
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 percent 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, like a ripe peach or a tall glass of Newman’s Own Virgin Limeade — which our local supermarket chain has, to our personal devastation, suddenly stopped selling, so please, liver, get a grip.
Scientists have also discovered that hepatocytes, the metabolically active cells that constitute 80 percent of the liver, possess traits not seen in any other normal cells of the body. For example, whereas most cells have two sets of chromosomes — two sets of genetic instructions on how a cell should behave — hepatocytes can enfold and deftly manipulate up to eight sets of chromosomes, and all without falling apart or turning cancerous.
That sort of composed chromosomal excess, said Dr. Markus Grompe, who studies the phenomenon at Oregon Health and Science University, is “superunique,” and most likely helps account for the liver’s regenerative prowess.
俄勒冈卫生科技大学(Oregon Health and Science University)的马库斯·葛鲁普(Markus Grompe)博士对这种沉着冷静的染色体过量现象进行了研究，他说该现象是“超级独一无二的”，很可能有助于解释肝脏的再生能力。
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.
“这很有趣。”西奈山医学院(Mount Sinai School of Medicine)的肝脏专家瓦莱丽·古文-埃文斯(Valerie Gouon-Evans)说：“肝脏不是一个很性感的器官。看起来不怎么重要。它看起来不过是一大团难以名状的东西。”
“But it is quietly vital, the control tower of the body,” and the hepatocytes that it is composed of “are astonishing.”
The liver is our largest internal organ, weighing 3 1/2 pounds and measuring 6 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 percent 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. That portal blood delivers semi-processed foodstuffs in need of hepatic massaging, conversion, detoxification, storage, secretion and elimination.
“Everything you put in your mouth must go through the liver before it does anything useful elsewhere in the body,” Lok said.
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,” Gillum said. “At some level it knows more than the brain does about energy availability, and whether you’re eating too many pears.”
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.
肝脏也会追踪时间变化。在最近一期的《细胞》(Cell)杂志上，日内瓦大学(University of Geneva)的乌尔里克·希布勒(Ulrich Schibler)及同事描述了他们对肝脏收缩所做的研究，提到它每天如何随动物的正常生理节律和进食规律膨胀与收缩。
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?” Schibler 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 Schibler suggested it is part of the organ’s fastidious maintenance program.
“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.”