Featured Research

from universities, journals, and other organizations

New leads for liver disease treatments: Strict genomic partitioning by biological clock separates key metabolic functions

Date:
July 31, 2014
Source:
University of California - Irvine
Summary:
Much of the liver's metabolic function is governed by circadian rhythms -- our own body clock -- and researchers have now found two independent mechanisms by which this occurs.

Much of the liver's metabolic function is governed by circadian rhythms -- our own body clock -- and UC Irvine researchers have now found two independent mechanisms by which this occurs.

The study, published online today in Cell, reveals new information about the body clock's sway over metabolism and points the way to more focused drug treatments for liver disease and such metabolic disorders as obesity and diabetes.

Paolo Sassone-Corsi, UCI's Donald Bren Professor of Biological Chemistry, and postdoctoral scholar Selma Masri report that two of these circadian-linked proteins, SIRT1 and SIRT6, manage important liver processes -- lipid storage and energy usage in liver cells -- separately and distinctly from each other.

This surprising discovery of genomic partitioning, Masri noted, reveals how strictly regulated circadian control of metabolism can be.

"The ability of the genome and epigenome to cross-talk with metabolic pathways is critical for cellular and organismal functions. What's remarkable is that the circadian clock is intimately involved in this dialogue," she said.

Circadian rhythms of 24 hours govern fundamental physiological functions in virtually all organisms. The circadian clocks are intrinsic time-tracking systems in our bodies that anticipate environmental changes and adapt themselves to the appropriate time of day. Changes to these rhythms can profoundly influence human health. Up to 15 percent of people's genes are regulated by the day-night pattern of circadian rhythms; nearly 50 percent of those involved with metabolic pathways in the liver are influenced by these rhythms.

SIRT1 and SIRT6 belong to a group of proteins called sirtuins that participate in epigenetic control of the genome and help regulate important biological processes ranging from cell health maintenance to lipid storage and energy expenditure in cells. They're widely studied for their effect on metabolism and longevity.

To discover how SIRT1 and SIRT6 work independently of each other, Masri and Sassone-Corsi conducted tests with two sets of mice -- one with SIRT1 in the liver knocked out and the other with SIRT6 nullified.

The two sirtuins, the scientists learned, are committed to the control of distinct genomic domains, with hundreds of genes being SIRT1-dependent and hundreds of others relying on SIRT6. This resulted in a distinct partition of metabolic pathways and physiological functions, Sassone-Corsi said.

He added that these findings pave the way to further investigations that may facilitate the design of pharmacological strategies targeting SIRT1- or SIRT6-specific metabolic functions and pathologies.

Paul Rigor, Marlene Cervantes, Nicholas Ceglia and Pierre Baldi of UC Irvine; Carlos Sebastian and Raul Mostoslavsky of Harvard Medical School; Cuiying Xiao and Chuxia Deng of the National Institutes of Health; and Timothy Osborne of the Sanford-Burnham Medical Research Institute in Orlando, Fla., contributed to the study, which received support from the National Institutes of Health (grants GM097899, LM010235, LM07443 and AG043745), the National Science Foundation (grant IIS-1321053), the Merieux Research Institute and Sirtris Pharmaceuticals.


Story Source:

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


Journal Reference:

  1. Selma Masri, Paul Rigor, Marlene Cervantes, Nicholas Ceglia, Carlos Sebastian, Cuiying Xiao, Manuel Roqueta-Rivera, Chuxia Deng, TimothyF. Osborne, Raul Mostoslavsky, Pierre Baldi, Paolo Sassone-Corsi. Partitioning Circadian Transcription by SIRT6 Leads to Segregated Control of Cellular Metabolism. Cell, 2014; 158 (3): 659 DOI: 10.1016/j.cell.2014.06.050

Cite This Page:

University of California - Irvine. "New leads for liver disease treatments: Strict genomic partitioning by biological clock separates key metabolic functions." ScienceDaily. ScienceDaily, 31 July 2014. <www.sciencedaily.com/releases/2014/07/140731145931.htm>.
University of California - Irvine. (2014, July 31). New leads for liver disease treatments: Strict genomic partitioning by biological clock separates key metabolic functions. ScienceDaily. Retrieved September 18, 2014 from www.sciencedaily.com/releases/2014/07/140731145931.htm
University of California - Irvine. "New leads for liver disease treatments: Strict genomic partitioning by biological clock separates key metabolic functions." ScienceDaily. www.sciencedaily.com/releases/2014/07/140731145931.htm (accessed September 18, 2014).

Share This



More Health & Medicine News

Thursday, September 18, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

The Cost of Ebola

The Cost of Ebola

Reuters - Business Video Online (Sep. 18, 2014) As Sierra Leone prepares for a three-day "lockdown" in its latest bid to stem the spread of Ebola, Ciara Lee looks at the financial implications of fighting the largest ever outbreak of the disease. Video provided by Reuters
Powered by NewsLook.com
What HealthKit Bug Means For Your iOS Fitness Apps

What HealthKit Bug Means For Your iOS Fitness Apps

Newsy (Sep. 18, 2014) Apple has delayed the launch of the HealthKit app platform, citing a bug. Video provided by Newsy
Powered by NewsLook.com
Residents Vaccinated as Haiti Fights Cholera Epidemic

Residents Vaccinated as Haiti Fights Cholera Epidemic

AFP (Sep. 18, 2014) Haitians receive the second dose of the vaccine against cholera as part of the UN's vaccination campaign. Duration: 00:34 Video provided by AFP
Powered by NewsLook.com
Raw: Elephant Undergoes Surgery in Tbilisi Zoo

Raw: Elephant Undergoes Surgery in Tbilisi Zoo

AP (Sep. 18, 2014) Grand the elephant has successfully undergone surgery to remove a portion of infected tusk at Tbilisi Zoo in Georgia. British veterinary surgeons used an electric drill to extract the infected piece. (Sept. 18) Video provided by AP
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