Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Molecular clock genes influence metabolism of sugar and dietary fats

02.11.2004


Implications for better understanding of diabetes, metabolic syndrome, and obesity



Researchers at the University of Pennsylvania School of Medicine have discovered that components of the internal molecular clock of mammals have an important role in governing the metabolism of sugars and fats within the body. They found in mice that two of the well-studied proteins in the clock control the ability of animals to recover from the fall in blood sugar that occurs in response to insulin.

The investigators demonstrate a role for the circadian clock proteins, Bmal1 and Clock, in regulating the day-to-day levels of glucose in the blood. Suppressing the action of these molecules eliminates the diurnal variation in glucose and triglyceride levels. In addition, they found that a mutated Clock gene protected mice from diabetes induced by a high-fat diet. Together these findings represent the first molecular insight into how timing of what we eat – via the clock – can influence metabolism. The findings appear in the November 2 issue of the online journal PLoS Biology.


The master molecular clock in mammals is located in the brain in an area called the suprachiasmatic nucleus, clusters of neurons in the hypothalamus. Many of our basic functions, including regulating body temperature and hormone levels, vary throughout the day and night. Some of these changes may relate to being asleep or awake and on the job, but others are under the control of a biochemical timepiece that sets and resets daily.

Over the last several years, researchers have begun to appreciate that the molecular components of the clock exist in most, if not all, tissues of the body. Some years ago, a team led by senior author Garret FitzGerald, MD, Chairman of Penn’s Department of Pharmacology, discovered a molecular clock in the heart and blood vessels and described for the first time how the master clock in the brain could use a hormone to control such a peripheral clock.

During the course of the group’s research they found that many metabolic genes were among the roughly 10 percent of genes that oscillate in activity in a 24-hour period. "We noticed a variation in the recovery of blood glucose with clock time," says Dan Rudic, PhD, a Research Associate in the Department of Pharmacology and a lead author on the current study. "We were stunned when we found that inactivating clock genes abolished this response."

Food is also an important cue in directing the daily oscillations of metabolism and blood-sugar levels. As such, what you eat, as well as how much and when, all interact with this process. Normally, after eating, insulin notifies several organs to take up excess sugar in the blood and store it as glycogen. Conversely, when the sugar level in blood dips between snacks, glucagon notifies the body to break down stored energy like glycogen and fat to release as glucose. The molecular clock genes work somehow to orchestrate this complex system. However, when this finely tuned scenario is upset, all-too-familiar diseases arise: diabetes when there is too much sugar; hypoglycemia when there is too little.

What’s more, the researchers found that a high-fat diet amplified the oscillation in blood sugar over a 24-hour period and that disabling the Clock gene markedly reduced this effect. Indeed, a mutated Clock gene protected mice from diabetes induced by a high fat diet, a model of type-2 diabetes in humans. How this works is as yet unclear, but the researchers think that the clock mediates the impact of a fatty diet. "This suggests that altering when fat calories are eaten might be exploited to reduce the likelihood of inducing diabetes," says FitzGerald.

Poor dietary habits and a sedentary lifestyle have been linked to diabetes, high blood fats, and high blood pressure, all characterized in an epidemic called metabolic syndrome, which is reaching alarming proportions in both developed and developing countries, says FitzGerald. This work adds to the understanding of physiological control of metabolism and therefore possibilities of working with the body’s natural rhythms to fight disease.

Over time humans have moved from eating our fill at one sitting after the hunt to continuous availability of fast food. Nutritionists have long speculated that it might matter whether we "nibble" or "gorge" our calories, and that this makes a difference in how our bodies handle a high-fat diet. "These results suggest that it may not just be what we eat, but also, to some extent, when we eat it," concludes FitzGerald.

Karen Kreeger | EurekAlert!
Further information:
http://www.uphs.upenn.edu

More articles from Life Sciences:

nachricht Ambush in a petri dish
24.11.2017 | Friedrich-Schiller-Universität Jena

nachricht Meadows beat out shrubs when it comes to storing carbon
23.11.2017 | Norwegian University of Science and Technology

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: New proton record: Researchers measure magnetic moment with greatest possible precision

High-precision measurement of the g-factor eleven times more precise than before / Results indicate a strong similarity between protons and antiprotons

The magnetic moment of an individual proton is inconceivably small, but can still be quantified. The basis for undertaking this measurement was laid over ten...

Im Focus: Frictional Heat Powers Hydrothermal Activity on Enceladus

Computer simulation shows how the icy moon heats water in a porous rock core

Heat from the friction of rocks caused by tidal forces could be the “engine” for the hydrothermal activity on Saturn's moon Enceladus. This presupposes that...

Im Focus: Nanoparticles help with malaria diagnosis – new rapid test in development

The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.

Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

IceCube experiment finds Earth can block high-energy particles from nuclear reactions

24.11.2017 | Physics and Astronomy

A 'half-hearted' solution to one-sided heart failure

24.11.2017 | Health and Medicine

Heidelberg Researchers Study Unique Underwater Stalactites

24.11.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>