Navigation Links
Natural brain substance blocks weight gain in mice, UT Southwestern researchers discover
Date:1/27/2009

DALLAS Jan. 28, 2009 Mice with increased levels of a natural brain chemical don't gain weight when fed a high-fat diet, researchers at UT Southwestern Medical Center have found.

The chemical, orexin, works by increasing the body's sensitivity to the "weight-loss hormone," leptin, the researchers report.

Finding a way to boost the orexin system may prove useful as a therapy against obesity, said Dr. Masashi Yanagisawa, professor of molecular genetics at UT Southwestern and senior author of the study, which appears in the January issue of Cell Metabolism.

"Obese people are not deficient in leptin," Dr. Yanagisawa said. "They have tons of leptin floating around. The problem is that their brain isn't very sensitive to it." Orexin, which Dr. Yanagisawa discovered about a decade ago, is involved in controlling appetite and sleep. He found that reduced levels of orexin lead to the sleep disorder narcolepsy in both rodents and humans.

Orexin can boost the appetite in the short term, but, paradoxically, a lack of orexin leads to obesity in the long run. "It's been confusing," said Dr. Yanagisawa, an investigator with the Howard Hughes Medical Institute at UT Southwestern.

Part of the confusion comes about because orexin acts on two different molecules in the brain, OX1R and OX2R. In the current study, the researchers aimed to distinguish which action was involved in weight control.

The researchers increased the levels of orexin in mice, either through genetic engineering or by administering the hormone into the brain.

When these mice were fed a healthy diet, the increased levels of orexin made little difference in their weights compared to normal mice; however, when the mice were fed a high-fat diet, the high-orexin mice remained lean while the normal animals became obese. This difference was due to an increase in the rate of metabolism high-orexin mice burned fuel up to 20 percent faster than normal mice.

The high-orexin mice had lower blood levels of leptin, implying that the leptin was more effective in controlling weight in these mice. In addition, when the researchers administered leptin to the high-orexin mice, the animals responded with a much greater loss of appetite and weight compared to normal mice given leptin.

The researchers also administered a substance that activates only OX2R to separate out orexin's possible double action. The mice given this substance showed the same beneficial response to high-fat diets and leptin, confirming that OX2R controls the interaction.

These results clarify the action of orexin and point to OX2R as a potential route to help treat obesity, but any practical use is still far off, Dr. Yanagisawa said.

A primary hurdle to orexin-based drug development is a defense system in the body called the blood-brain barrier, which prevents many substances in the blood from penetrating into the brain. Because of this, orexin cannot reach the brain when it is given orally or as an intravenous or subcutaneous injection.

"Fortunately, however, high-orexin mice show no sleep/wake disturbance or other serious side effects," Dr. Yanagisawa said.

"This study suggests that if we can develop a compound that mimics the action of orexin on its receptor, we might be able to treat narcolepsy and other sleep disorders, as well as obesity," Dr. Yanagisawa said. "We have already screened out some such 'orexin mimics.' The next step is to do serious medicinal chemistry to make variations of these compounds to get them more potent and specific. If we could advance to early clinical trials in five years, I'd say we'd be lucky.

"I hope that in the long run a suitable orexin mimic might help people be more mentally productive during the day, as well as be able to lose weight more easily."


'/>"/>

Contact: Aline McKenzie
aline.mckenzie@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center
Source:Eurekalert  

Related biology news :

1. Natural chemical found in broccoli helps combat skin blistering disease
2. Natural insecticide re-created in the lab
3. Researchers develop simple method to create natural drug products
4. Brains timing linked with timescales of the natural visual world
5. Alternative methods proposed to detect pesticides and antibiotics in water and natural food
6. Naturally-occurring apple compounds reduce risk of pancreatic cancer
7. New membrane strips carbon dioxide from natural gas faster and better
8. Natural product discovery by Cleveland medical researchers blocks tissue destruction
9. MU researchers go nano, natural and green
10. Researchers discover natural herbicide released by grass
11. Baker Institute finds increased domestic production wont make US self-sufficient in natural gas
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Natural brain substance blocks weight gain in mice, UT Southwestern researchers discover
(Date:6/2/2016)... 2016   The Weather Company , an IBM Business ... industry-first capability in which consumers will be able to interact ... questions via voice or text and receive relevant information about ... Marketers have long sought an advertising solution that can ... personal, relevant and valuable; and can scale across millions of ...
(Date:5/16/2016)... May 16, 2016   EyeLock LLC , a ... the opening of an IoT Center of Excellence in ... expand the development of embedded iris biometric applications. ... of convenience and security with unmatched biometric accuracy, making ... aside from DNA. EyeLock,s platform uses video technology to ...
(Date:4/28/2016)... GOTHENBURG, Sweden , April 28, 2016 ... 1,491.2 M (139.9), up 966% compared with the first quarter of ... Operating profit totaled SEK 589.1 M (loss: 18.8) and the operating ... SEK 7.12 (loss: 0.32) Cash flow from operations was ... , The 2016 revenue guidance is unchanged, SEK 7,000-8,500 M. ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... 2016 Apellis Pharmaceuticals, Inc. today announced ... of its complement C3 inhibitor, APL-2. The trials ... dose studies designed to assess the safety, tolerability, ... in healthy adult volunteers. Forty subjects ... single dose (ranging from 45 to 1,440mg) or ...
(Date:6/23/2016)... -- Andrew D Zelenetz , ... Published recently in Oncology & ... Andrew D Zelenetz , discusses the fact ... placing an increasing burden on healthcare systems worldwide, ... the patents on many biologics expiring, interest in ...
(Date:6/23/2016)... ... June 23, 2016 , ... ClinCapture, the only free ... and will showcase its product’s latest features from June 26 to June 30, ... poster on Disrupting Clinical Trials in The Cloud during the conference. DIA ...
(Date:6/23/2016)... Connecticut (PRWEB) , ... June 23, 2016 , ... ... introduce a new line of intelligent tools designed, tuned and optimized exclusively for ... September 12–17 in Chicago. The result of a collaboration among several companies with ...
Breaking Biology Technology: