Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

A Healthy Internal Clock Keeps Weight Off

25.04.2005


Staying up past bedtime, skipping meals, and snacking constantly all add up to weight gain, fatty livers, and high cholesterol levels for an unlucky group of mice whose internal biological clocks are genetically disrupted.



Researchers at Northwestern University and the Howard Hughes Medical Institute have identified wide-ranging molecular and behavioral changes in mice that have a faulty circadian system. In people, similar changes in body fat and metabolic activity are known as metabolic syndrome, which can lead to cardiovascular disease and type 2 diabetes.

The research team, which included co-author Joseph S. Takahashi, a Howard Hughes Medical Institute investigator at Northwestern University, published its report on April 21, 2005, in Science Express, which provides rapid electronic publication of select articles from the journal Science. The study suggests a surprising new angle for understanding and eventually preventing and treating obesity and related disorders in people.


"Timing is critical to keep the metabolic symphony in tune," said corresponding author Joseph Bass, assistant professor of medicine and neurobiology at Northwestern University and head of the endocrinology and metabolism division at Evanston Northwestern Healthcare. Quoting Duke Ellington, Bass added, "It don’t mean a thing if it ain’t got that swing.”

The mice have defective Clock genes that control daily rhythms in the brain and throughout the body, including sleeping and eating. The gene was discovered eight years ago by Takahashi’s laboratory. Since then, Takahashi and other researchers have shown that the Clock gene and a half-dozen other proteins run 24-hour oscillating clocks in most cells in the body and in a specific part of the brain that controls appetite and wakefulness. About 3-10 percent of the genes in any given tissue turn on and off in circadian rhythm.

The project started when circadian rhythm expert Fred Turek, lead author of the paper and professor of neurobiology and physiology at Northwestern, noticed that the Clock mutant mice gained more weight with age than other mice.

Experiments soon revealed the cause. Mice with the mutant Clock gene ate more than normal mice, so they gained more weight, especially on a high-fat diet, which was evident within six weeks of birth. The chubby Clock mutants put on about as much extra weight as did the normal mice that were switched to a high fat diet.

The Clock mutant mice lost both their alarm clocks and their internal dinner bells. Mice typically sleep during the day and then eat a meal at the beginning and at the end of their active nocturnal day, akin to breakfast and dinner. Instead, the Clock mutant mice skipped their meals, stayed awake far into the usual rest time, and snacked often.

The insomniac mice also were a little more sluggish, as measured by infrared sensors in their cages. The researchers removed the exercise wheels normally used to gauge mouse activity, because regular spins can help the mice reset their biological clocks, just as a daily walk might help a person sleep better at night.

In repeated round-the-clock measurements, the researchers found signs of further trouble emerging in the mice’s early adult months. The circadian-challenged mice developed high cholesterol, high triglycerides, high blood sugar, low insulin, bloated fat cells, and lipid-engorged liver cells. Some of these changes appeared to be independent of the weight gain, Bass said.

Using sensitive techniques in Takahashi’s lab, the researchers found changes in the key proteins in the hypothalamic region of the brain that manages feeding, energy balance, and sleep-wake regulation. Takahashi and his colleagues suspect the metabolic changes are caused more directly by misregulated genes in various tissues normally controlled by the Clock gene, rather than by the effects of the weight gain.

"It’s like an orchestra," said Bass, a former HHMI postdoctoral fellow. "The tissues important in metabolism have to be conducted properly. But in the Clock mutant, each tissue plays to its own beat, which creates cacophony at the biological level that sets up the animal for obesity and metabolic disregulation."

"The Clock finding reinforces the idea of important interactions between circadian rhythms, sleep and metabolism," said Emmanuel Mignot, an HHMI investigator at Stanford University. He and his colleagues recently reported that even partial sleep deprivation changes the blood levels of several appetite-regulatory hormones, including leptin and Ghrelin, an effect likely to increase food intake and obesity in the general population. "The study also shows the importance of working across multiple scientific disciplines—in this case, circadian rhythm and energy metabolism," Mignot noted. "Indeed, who would have considered Clock as a metabolic candidate gene?"

Jennifer Michalowski | EurekAlert!
Further information:
http://www.hhmi.org

More articles from Health and Medicine:

nachricht Study suggests possible new target for treating and preventing Alzheimer's
02.12.2016 | Oregon Health & Science University

nachricht The first analysis of Ewing's sarcoma methyloma opens doors to new treatments
01.12.2016 | IDIBELL-Bellvitge Biomedical Research Institute

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

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,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

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

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>