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 Blood test shows promise for early detection of severe lung-transplant rejection
23.01.2019 | NIH/National Heart, Lung and Blood Institute

nachricht Evolution of signaling molecules opens door to new sepsis therapy approaches
23.01.2019 | Technische Universität München

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Bifacial Stem Cells Produce Wood and Bast

Heidelberg researchers study one of the most important growth processes on Earth

So-called bifacial stem cells are responsible for one of the most critical growth processes on Earth – the formation of wood.

Im Focus: Energizing the immune system to eat cancer

Abramson Cancer Center study identifies method of priming macrophages to boost anti-tumor response

Immune cells called macrophages are supposed to serve and protect, but cancer has found ways to put them to sleep. Now researchers at the Abramson Cancer...

Im Focus: Ten-year anniversary of the Neumayer Station III

The scientific and political community alike stress the importance of German Antarctic research

Joint Press Release from the BMBF and AWI

The Antarctic is a frigid continent south of the Antarctic Circle, where researchers are the only inhabitants. Despite the hostile conditions, here the Alfred...

Im Focus: Ultra ultrasound to transform new tech

World first experiments on sensor that may revolutionise everything from medical devices to unmanned vehicles

The new sensor - capable of detecting vibrations of living cells - may revolutionise everything from medical devices to unmanned vehicles.

Im Focus: Flying Optical Cats for Quantum Communication

Dead and alive at the same time? Researchers at the Max Planck Institute of Quantum Optics have implemented Erwin Schrödinger’s paradoxical gedanken experiment employing an entangled atom-light state.

In 1935 Erwin Schrödinger formulated a thought experiment designed to capture the paradoxical nature of quantum physics. The crucial element of this gedanken...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Our digital society in 2040

16.01.2019 | Event News

11th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Aachen, 3-4 April 2019

14.01.2019 | Event News

ICTM Conference 2019: Digitization emerges as an engineering trend for turbomachinery construction

12.12.2018 | Event News

 
Latest News

A New Home for Optical Solitons

23.01.2019 | Physics and Astronomy

Graphene and related materials safety: human health and the environment

23.01.2019 | Materials Sciences

Blood test shows promise for early detection of severe lung-transplant rejection

23.01.2019 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>