Featured Research

from universities, journals, and other organizations

It's about time: Disrupted internal clocks play role in disease

Date:
July 1, 2013
Source:
Northwestern University
Summary:
Researchers have a possible explanation why some alcoholics develop liver disease: Disrupted circadian rhythms can push those vulnerable over the edge to disease. Mice whose internal clocks were out of sync with the light-dark cycle and mice with circadian disruption from a faulty gene were fed diets without and with alcohol. The results showed circadian rhythm disruption and alcohol is a destructive double hit that can lead to alcoholic liver disease.

Thirty percent of severe alcoholics develop liver disease, but scientists have not been able to explain why only a subset is at risk. A research team from Northwestern University and Rush University Medical Center now has a possible explanation: disrupted sleep and circadian rhythms can push those vulnerable over the edge to disease.

The team studied mice that essentially were experiencing what shift workers or people with jet lag suffer: their internal clocks were out of sync with the natural light-dark cycle. Another group of mice had circadian disruption due to a faulty gene. Both groups were fed a diet without alcohol and next with alcohol, and the team then examined the physiological effects.

The researchers found the combination of circadian rhythm disruption and alcohol is a destructive double hit that can lead to alcoholic liver disease.

The study was published last month by the journal PLOS ONE.

"Circadian disruption appears to be a previously unrecognized risk factor underlying the susceptibility to or development of alcoholic liver disease," said Fred W. Turek, the Charles E. and Emma H. Morrison Professor of Biology at Northwestern's Weinberg College of Arts and Sciences and one of the senior authors of the paper.

"What we and many other investigators are doing is bringing time to medicine for the diagnosis and treatment of disease," Turek said. "We call it circadian medicine, and it will be transformative. Medicine will change a great deal, similar to the way physics changed when Einstein brought time to physics."

A number of years ago, Ali Keshavarzian, M.D., a gastroenterologist at Rush University Medical Center who has worked with and studied patients with gastrointestinal and liver diseases, had a hunch disrupted circadian rhythms could be a contributing factor to the disease.

Keshavarzian had noticed that some patients with inflammatory bowel disease (inflammation in the intestine and/or colon) had flare-ups of symptoms when working nights, but they could control the disease when working the day shift. He sought out Turek, director of Northwestern's Center for Sleep and Circadian Biology, to help investigate the relationship between circadian rhythms and the disease.

The two investigators and their groups first studied the effect of circadian rhythm disruption in an animal model of colitis and noted that disruption of sleep and circadian rhythms (caused by modeling shift work and chronic jet lag in the animals) caused more severe colitis in mice.

Keshavarzian has been studying the effect of "gut leakiness" (the intestinal lining becomes weak and causes dangerous endotoxins to get into the blood stream) to bacterial products in gastrointestinal diseases for two decades. Because the mouse model of colitis is associated with leaky gut, he proposed that disruption of circadian rhythms from shift work could make the intestine more susceptible to leakiness. He wanted to test its effect in an animal model of alcoholic liver disease -- where a subset of alcoholics develop gut leakiness and liver disease -- in order to find out whether shift work is the susceptibility factor that promotes liver injury.

"Non-pathogen-mediated chronic inflammation is a major cause of many chronic diseases common in Western societies and developing countries that have adopted a Western lifestyle," said Keshavarzian, one of the senior authors of the paper. He is director of the Division of Digestive Diseases and the Josephine M. Dyrenforth Chair of Gastroenterology.

Crohn's and ulcerative colitis, Parkinson's disease, diabetes, multiple sclerosis, autoimmune disease and cardiovascular disease are examples of these diseases, to name just a few.

"Recent studies have shown that intestinal bacteria are the primary trigger for this inflammation, and gut leakiness is one of the major causes," Keshavarzian said. "The factor leading to gut leakiness is not known, however. Our study suggests that disruption of circadian rhythms and sleep, which is part of life in industrial societies, can promote it and explain the susceptibility."

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."


Story Source:

The above story is based on materials provided by Northwestern University. Note: Materials may be edited for content and length.


Journal Reference:

  1. Keith C. Summa, Robin M. Voigt, Christopher B. Forsyth, Maliha Shaikh, Kate Cavanaugh, Yueming Tang, Martha Hotz Vitaterna, Shiwen Song, Fred W. Turek, Ali Keshavarzian. Disruption of the Circadian Clock in Mice Increases Intestinal Permeability and Promotes Alcohol-Induced Hepatic Pathology and Inflammation. PLoS ONE, 2013; 8 (6): e67102 DOI: 10.1371/journal.pone.0067102

Cite This Page:

Northwestern University. "It's about time: Disrupted internal clocks play role in disease." ScienceDaily. ScienceDaily, 1 July 2013. <www.sciencedaily.com/releases/2013/07/130701163944.htm>.
Northwestern University. (2013, July 1). It's about time: Disrupted internal clocks play role in disease. ScienceDaily. Retrieved July 25, 2014 from www.sciencedaily.com/releases/2013/07/130701163944.htm
Northwestern University. "It's about time: Disrupted internal clocks play role in disease." ScienceDaily. www.sciencedaily.com/releases/2013/07/130701163944.htm (accessed July 25, 2014).

Share This




More Health & Medicine News

Friday, July 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Beatings and Addiction: Pakistan Drug 'clinic' Tortures Patients

Beatings and Addiction: Pakistan Drug 'clinic' Tortures Patients

AFP (July 24, 2014) — A so-called drugs rehab 'clinic' is closed down in Pakistan after police find scores of ‘patients’ chained up alleging serial abuse. Duration 03:05 Video provided by AFP
Powered by NewsLook.com
Too Few Teens Receiving HPV Vaccination, CDC Says

Too Few Teens Receiving HPV Vaccination, CDC Says

Newsy (July 24, 2014) — The Centers for Disease Control and Prevention is blaming doctors for the low number of children being vaccinated for HPV. Video provided by Newsy
Powered by NewsLook.com
New Painkiller Designed To Discourage Abuse: Will It Work?

New Painkiller Designed To Discourage Abuse: Will It Work?

Newsy (July 24, 2014) — The FDA approved Targiniq ER on Wednesday, a painkiller designed to keep users from abusing it. Like any new medication, however, it has doubters. Video provided by Newsy
Powered by NewsLook.com
Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Newsy (July 24, 2014) — Sheik Umar Khan has treated many of the people infected in the Ebola outbreak, and now he's become one of them. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

    Health News

      Environment News

        Technology News



          Save/Print:
          Share:  

          Free Subscriptions


          Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

          Get Social & Mobile


          Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

          Have Feedback?


          Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
          Mobile iPhone Android Web
          Follow Facebook Twitter Google+
          Subscribe RSS Feeds Email Newsletters
          Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins