Scientists create compounds that dramatically alter biological clock and lead to weight loss
March 29, 2012 in Medical research
Scientists from the Florida campus of The Scripps Research Institute have synthesized a pair of small molecules that dramatically alter the core biological clock in animal models, highlighting the compounds' potential effectiveness in treating a remarkable range of disordersincluding obesity, diabetes, high cholesterol, and serious sleep disorders.
The study was published on March 29, 2012, in an advance, online edition of the journal Nature.
The study showed that when administered in animal models the synthetic small molecules altered circadian rhythm and the pattern of core clock gene expression in the brain's hypothalamus, the site of the master cellular clock that synchronizes daily rhythms in mammals; circadian rhythms are the physiological processes that respond to a 24-hour cycle of light and dark and are present in most living things.
When given to diet-induced obese mice, these same small molecules decreased obesity by reducing fat mass and markedly improving cholesterol levels and hyperglycemiachronically high blood sugar levels that frequently lead to diabetes.
"The idea behind this research is that our circadian rhythms are coupled with metabolic processes and that you can modulate them pharmacologically," said Thomas Burris, a professor at Scripps Florida who led the study. "As it turns out, the effect of that modulation is surprisingly positiveeverything has been beneficial so far."
Burris stressed that these compounds were first generationthe first to hit their targets in vivo with room for improvement as potential treatments. "In terms of therapeutics, this is really the first step," he said.
In the new study, the team identified and tested a pair of potent synthetic compounds that activate proteins called REV-ERBα and REV-ERBβ, which play an integral role in regulating the expression of core clock proteins that drive biological rhythms in activity and metabolism.
In the study, the scientists observed clear metabolic effects when the synthetic compounds were administered twice a day for 12 days. Animals displayed weight loss due to decreased fat mass with no changes in the amount of food they ate. The animals followed the human model of obesity closely, eating a standard Western diet of high fat, high sugar foods, yet still lost weight when given the compounds.
In one of the study's more striking findings, both synthetic compounds were shown to reduce cholesterol production. Cholesterol in the blood of treated animal models decreased 47 percent; triglycerides in the blood decreased 12 percent.
The circadian pattern of expression of a number of metabolic genes in the liver, skeletal muscle, and in fat tissue was also altered, resulting in increased energy expenditure, something of a surprise. In the study, the scientists observed a five percent increase in oxygen consumption, suggesting increased energy expenditure during the day and at night. However, these increases were not due to increased activitythe animals displayed an overall 15 percent decrease in movement during those same time periods.
In addition to its impact on metabolism, the two compounds also affected the animals' activity during periods of light and darkness, suggesting that this class of compound may be useful for the treatment of sleep disorders, including the common problem of jet lag.
More information: "Regulation of Circadian Behavior and Metabolism by Synthetic REV‐ERB Agonists," Nature.
Journal reference:
Nature
Provided by
The Scripps Research Institute
-
Scientists identify new mechanism regulating daily biological rhythms
Nov 11, 2010 |
not rated yet |
0
-
Another reason to avoid high-fat diet -- it can disrupt our biological clock
Dec 29, 2008 |
not rated yet |
0
-
Scientists find high-fat diet disrupts body clock
Nov 06, 2007 |
not rated yet |
0
-
Clock gene plays role in weight gain, study finds
May 17, 2007 |
not rated yet |
0
-
Feeding the clock: Cycles of feeding and fasting drive circadian gene expression in the liver
Nov 25, 2009 |
not rated yet |
0
-
Motion perception revisited: High Phi effect challenges established motion perception assumptions
Apr 23, 2013 |
3 / 5 (2) |
2
-
Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update)
Apr 02, 2013 |
4.5 / 5 (11) |
5
-
The visual system as economist: Neural resource allocation in visual adaptation
Mar 30, 2013 |
5 / 5 (2) |
9
-
Separate lives: Neuronal and organismal lifespans decoupled
Mar 27, 2013 |
4.9 / 5 (8) |
0
-
Sizing things up: The evolutionary neurobiology of scale invariance
Feb 28, 2013 |
4.8 / 5 (10) |
14
-
How can there be a term called "intestinal metaplasia" of stomach
18 hours ago
-
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013
-
If you became brain-dead, would you want them to pull the plug?
May 17, 2013
-
MRI bill question
May 15, 2013
-
Ratio of Hydrogen of Oxygen in Dessicated Animal Protein
May 13, 2013
-
Alcohol and acetaminophen
May 13, 2013
- More from Physics Forums - Medical Sciences
More news stories
H. pylori, smoking trends, and gastric cancer in US men
Trends in Helicobacter pylori (H. pylori) and smoking explain a significant proportion of the decline of intestinal-type noncardia gastric adenocarcinoma (NCGA) incidence in US men between 1978 and 2008, and are estimated ...
Medical research
7 hours ago |
not rated yet |
0
Common food supplement fights degenerative brain disorders
Widely available in pharmacies and health stores, phosphatidylserine is a natural food supplement produced from beef, oysters, and soy. Proven to improve cognition and slow memory loss, it's a popular treatment for older ...
Medical research
12 hours ago |
5 / 5 (2) |
0
|
Finding a family for a pair of orphan receptors in the brain
Researchers at Emory University have identified a protein that stimulates a pair of "orphan receptors" found in the brain, solving a long-standing biological puzzle and possibly leading to future treatments for neurological ...
Medical research
12 hours ago |
5 / 5 (1) |
0
|
Insight into the dazzling impact of insulin in cells
Australian scientists have charted the path of insulin action in cells in precise detail like never before. This provides a comprehensive blueprint for understanding what goes wrong in diabetes.
Medical research
13 hours ago |
4.5 / 5 (6) |
0
|
Do men's and women's hearts burn fuel differently?
Researchers at the University of Illinois at Chicago College of Medicine will study gender differences in how the heart uses and stores fat—its main energy source—and how changes in fat metabolism play ...
Medical research
16 hours ago |
not rated yet |
0
If you can remember it, you can remember it wrong
(Medical Xpress)—Native peoples in regions where cameras are uncommon sometimes react with caution when their picture is taken. The fear that something must have been stolen from them to create the photo ...
B vitamins could delay dementia
(Medical Xpress)—Despite spending billions of dollars on research and development, drug companies have been unable to come up with effective treatments for dementia and Alzheimer's Disease (AD). Now, A. ...
New sleeping pill poised to hit US markets
An experimental sleeping pill from US drug company Merck is effective at helping people fall and stay asleep, according to reviewers at the US Food and Drug Administration, which could soon approve the new drug.
Reducing caloric intake delays nerve cell loss
Activating an enzyme known to play a role in the anti-aging benefits of calorie restriction delays the loss of brain cells and preserves cognitive function in mice, according to a study published in the May ...
Antidepressant reduces stress-induced heart condition
A drug commonly used to treat depression and anxiety may improve a stress-related heart condition in people with stable coronary heart disease, according to researchers at Duke Medicine.
Small cancer risk following CT scans in childhood and adolescence confirmed
The gap between life expectancy in patients with a mental illness and the general population has widened since 1985 and efforts to reduce this gap should focus on improving physical health, suggest researchers in a paper ...
Mar 29, 2012
Rank: not rated yet
It's freaking ridiculous what I'm dealing with trying to rehabilitate my muscles.
I don't know what the deal is, I just finished a stress test today, on top of two EKG over the past year, and they've determined it's not my heart. Even said my heart was exceptionally healthy.
But I can't even do more than like 1 set of 10 or 20 push-ups and leg raises and I'm whipped.
I'm not obese, but I do have quite a few extra pounds, but this is ridiculous.
My cousin is about my age, and no more active than me, and he's still strong as can be. Plus he IS obese, and his cholesterol is better without medication than mine is with medication!
Generalized Malaise, muscle weakness and soreness, low strength, low endurance, poor recovery, and find myself taking naps of 30 minutes to 2 hours in the middle of the day.
I'm only 31.
Mar 29, 2012
Rank: not rated yet
Mar 29, 2012
Rank: not rated yet
Due to medical conditions, when I was younger, I went from exercising almost every day to not at all for years. When I was finally able to start exercising again, I would be dead tired almost immediately. It took a good four months to feel good when jogging again but boy was it hell getting there.
Apr 01, 2012
Rank: not rated yet