Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

The Food-Energy Cellular Connection Revealed: Metabolic Master Switch Sets the Biological Clock in Body Tissues

19.10.2009
Our body's activity levels fall and rise to the beat of our internal drums-the 24-hour cycles that govern fundamental physiological functions, from sleeping and feeding patterns to the energy available to our cells. Whereas the master clock in the brain is set by light, the pacemakers in peripheral organs are set by food availability. The underlying molecular mechanism was unknown.

Now, researchers at the Salk Institute for Biological Studies shed light on the long missing connection: A metabolic master switch, which, when thrown, allows nutrients to directly alter the rhythm of peripheral clocks.

Since the body's circadian rhythm and its metabolism are closely intertwined, the risk for metabolic disease shoots up, when they are out of sync. "Shift workers face a 100 percent increase in the risk for obesity and its consequences, such as high blood pressure, insulin resistance and an increased risk of heart attacks," says Howard Hughes Medical Investigator Ronald M. Evans, Ph.D., a professor in the Salk Institute's Gene Expression Laboratory.

The researchers' findings, which are published in the Oct. 16, 2009, issue of Science, could have far-reaching implications, from providing a better understanding how nutrition and gene expression are linked, to creating new ways to treat obesity, diabetes and other related diseases. "It is estimated that the activity of up to 15 percent of our genes is under the direct control of biological clocks," says Evans. "Our work provides a conceptual way to link nutrition and energy regulation to the genome."

The clocks themselves keep time through the rhythmic waxing and waning of circadian gene expression on a roughly 24-hour schedule that anticipates environmental changes and adapts many of the body's physiological functions to the appropriate time of day. The most obvious one, the sleep-wake rhythm, is tightly linked to the night-day cycle. But so are physical activity and metabolism.

"When we get up in the morning we 'break the fast'," says Evans. While opening the fridge doesn't require a lot of physical activity, the situation for animals in the wild is quite different. "If you are a predatory animal you run to hunt. If you are prey, you run to get away."

But how pacemakers in peripheral tissues such as the liver and muscle knew that it was time to scurry and replenish their energy stores was still an open question. When postdoctoral researcher and first author Katja Lamia, Ph.D., started probing the relationship between metabolism and circadian cycles, she discovered a highly conserved phosporylation site in CRY1, short for cryptochrome 1. Cryptochromes originally evolved as a blue light photoreceptor in plants and, although no longer sensitive to light, are now an integral part of the clock in vertebrates.

The phosphorylation site is specific for AMPK, which acts like a gas gauge by sensing how much energy a cell has. When a cell has plenty of energy, AMPK remains inactive and the cell carries out its normal processes. Her experiments revealed that if a cell runs on empty, AMPK is turned on and attaches a phosphate molecule to CRY1, which initiates the destruction of CRY1. As a result the circadian rhythm speeds up and the clock is reset.

"The insertion of an AMPK phosphorylation site transformed a light sensor into an energy sensor, which now allows nutrients to provide metabolic input to circadian clocks," explain Lamia. "Insertion of a novel sensor into an existing signaling pathway is a very elegant solution to a rather complicated problem."

Genetic inactivation of AMPK in mice blocks these effects, stabilizing CRY1 and severely disrupting peripheral clocks. In contrast, treating mice with AICAR, a synthetic drug that directly activates AMPK, reset the clock in cultured cells as well as in animals, confirming that cryptochromes act as energy sensors that allow to circadian clocks.

Researchers who also contributed to the study include Uma M. Sachdeva and Craig B. Thompson at the Abramson Family Cancer Research Institute at the University of Pennsylvania School of Medicine in Philadelphia, Daniel F. Egan, Debbie S. Vasquez and Reuben Shaw in the Molecular and Cell Biology Laboratory, Elliot C. Williams and Henry Juguilon in the Gene Expression Laboratory as well as Luciano DiTacchio and Satchidananda Panda in the Regulatory Biology Laboratory, all at the Salk Institute for Biological Studies in La Jolla.

The work was funded in part by the National Institutes of Health, the Pew Charitable Trust and the Life Sciences Research Foundation.

About the Salk Institute for Biological Studies:

The Salk Institute for Biological Studies is one of the world's preeminent basic research institutions, where internationally renowned faculty probe fundamental life science questions in a unique, collaborative, and creative environment. Focused on both discovery and mentoring future generations of researchers, Salk scientists make groundbreaking contributions to our understanding of cancer, aging, Alzheimer's, diabetes, and cardiovascular disorders by studying neuroscience, genetics, cell and plant biology, and related disciplines.

Faculty achievements have been recognized with numerous honors, including Nobel Prizes and memberships in the National Academy of Sciences. Founded in 1960 by polio vaccine pioneer Jonas Salk, M.D., the Institute is an independent nonprofit organization and architectural landmark.

Gina Kirchweger | Newswise Science News
Further information:
http://www.salk.edu

More articles from Life Sciences:

nachricht Staying in Shape
16.08.2018 | Max-Planck-Institut für molekulare Zellbiologie und Genetik

nachricht Chips, light and coding moves the front line in beating bacteria
16.08.2018 | Okinawa Institute of Science and Technology (OIST) Graduate University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

Im Focus: Lining up surprising behaviors of superconductor with one of the world's strongest magnets

Scientists have discovered that the electrical resistance of a copper-oxide compound depends on the magnetic field in a very unusual way -- a finding that could help direct the search for materials that can perfectly conduct electricity at room temperatur

What happens when really powerful magnets--capable of producing magnetic fields nearly two million times stronger than Earth's--are applied to materials that...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

2018 Work Research Conference

25.07.2018 | Event News

 
Latest News

Staying in Shape

16.08.2018 | Life Sciences

Diving robots find Antarctic seas exhale surprising amounts of carbon dioxide in winter

16.08.2018 | Earth Sciences

Protein droplets keep neurons at the ready and immune system in balance

16.08.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>