In the study, the Northwestern and Rush researchers used two independent approaches, studying both genetic and environmental animal models. The circadian rhythms of one group of mice were disrupted genetically: Each animal had a mutant CLOCK gene, which regulates circadian rhythms. The second group's circadian rhythms were disrupted environmentally: The animals' light-dark cycle was changed periodically, leading to a state similar to chronic jet lag.
Mice in both groups, prior to ingesting alcohol, showed an increase in gut leakiness.
Next, both groups of mice were fed alcohol. After only one week, animals in both groups showed a significant additional increase in gut leakiness, compared to control mice on an alcohol-free diet. At the end of the three-month study, mice in both groups were in the early stages of alcoholic liver disease.
"We have clearly shown that circadian rhythm disruption can trigger gut leakiness, which drives the more severe pathology in the liver," said Keith Summa, a co-first author of the study and an M.D./Ph.D. candidate working in Turek's lab.
"For humans, circadian rhythm disruption typically is environmental, not genetic, so individuals have some control over the behaviors that cause trouble, be it a poor sleep schedule, shift work or exposure to light at night," he said.
Sleep and circadian rhythms are an integral part of biology and should be part of the discussion between medical doctors and their patients, the researchers believe.
"We want to personalize medicine from a time perspective," Turek said. "Our bodies are organized temporally on a 24-hour basis, and this needs to be brought into the equation for understanding health and disease."
|Contact: Megan Fellman|