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 What happens in the cell nucleus after fertilization
06.12.2016 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Researchers uncover protein-based “cancer signature”
05.12.2016 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Simple processing technique could cut cost of organic PV and wearable electronics

06.12.2016 | Materials Sciences

3-D printed kidney phantoms aid nuclear medicine dosing calibration

06.12.2016 | Medical Engineering

Robot on demand: Mobile machining of aircraft components with high precision

06.12.2016 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>