Featured Research

from universities, journals, and other organizations

Protein must exist in specific brain cells to prevent diet-induced obesity

Date:
July 7, 2010
Source:
UT Southwestern Medical Center
Summary:
A protein found in cells throughout the body must be present in a specific set of neurons in the brain to prevent weight gain after chronic feeding on high-calorie meals, new findings suggest.

A protein found in cells throughout the body must be present in a specific set of neurons in the brain to prevent weight gain after chronic feeding on high-calorie meals, new findings from UT Southwestern Medical Center researchers suggest.

Nicknamed the "longevity" protein because of its apparent role in mediating the effects of dietary restriction on life span, SIRT1 has been studied as a potential target for anti-aging drugs. Prior research also has shown that this metabolic sensor protein in peripheral tissues plays an important role in regulating metabolism, but its physiological relevance in brain neurons remained unclear.

"This is the first study to show that SIRT1 in hypothalamic neurons, specifically POMC neurons, is required for preventing diet-induced obesity and maintaining normal body weight," said Dr. Roberto Coppari, assistant professor of internal medicine at UT Southwestern and senior author of the mouse study, available online and in the July 7 issue of Cell Metabolism.

POMC, or pro-opiomelanocortin, neurons are found in the hypothalamus region of the brain and are known to play an important role in suppressing appetite and inducing weight loss. There are about 3,000 POMC neurons in a mouse brain.

The researchers genetically engineered mice to lack SIRT1 only in these specific hypothalamic neurons. They found that when fed a high-calorie diet, the mice lacking SIRT1 in POMC neurons gained more weight and were generally more susceptible to diet-induced obesity than those with the metabolic sensor protein intact.

The mutant mice also had almost twice as much abdominal fat and more of the hormone leptin than those mice with their SIRT1 intact, despite the fact that all the mice maintained the same food intake and movement levels.

"We found that SIRT1 must be present in POMC neurons in order for the hormone leptin to properly engage its receptors in these neurons. Without SIRT1, leptin sensing is altered and the animals gain more fat mass when fed a high-calorie diet," Dr. Coppari said.

In addition, the researchers found that SIRT1 must be present in POMC neurons for leptin to stimulate the remodeling of white adipose tissue into brown fat tissue, which "burns" fat to generate heat. White adipocytes primarily store fat.

"When SIRT1 is present in POMC neurons, the neurons properly convey a signal from leptin to the white perigonadal fat, which is designed to store energy. This signal is needed for the fat to undergo a remodeling process and expand the brown fat cells component as a protective measure against obesity," Dr. Coppari said. "If you don't have these kinds of defense mechanisms, you likely become hypersensitive to diet-induced obesity. A primary defect in SIRT1 in POMC neurons might be present in some individuals who are more prone to develop obesity when constantly exposed to an abundance of high-fat, high-calorie foods."

Dr. Coppari said the idea of a drug that selectively could target neurons controlling specific fat depots -- and that could trigger the remodeling of white fat into brown fat -- has high potential.

"The drawback to harnessing adrenergic receptors to make more brown adipocytes, as a lot of people are thinking about doing, is that it puts a lot of pressure on the cardiovascular system," he said. "However, the idea of having a drug that could selectively affect specific hypothalamic neurons that then control specific branches of the sympathetic nervous system suggests that one could avoid acting on unwanted cells but selectively on those able to burn calories such as brown adipocytes.

"We could control the remodeling of a particular fat depot into brown, which would then be more likely to cause weight loss without increasing the risk of cardiovascular problems," he said.

The next step, Dr. Coppari said, is to determine whether SIRT1 is mediating other signaling pathways in the brain that in addition to regulating body weight are key for normal glucose balance.

Other UT Southwestern researchers involved in the study were Dr. Giorgio Ramadori, lead author and postdoctoral researcher in internal medicine; Dr. Teppei Fujikawa, postdoctoral researcher in internal medicine; Drs. Makoto Fukuda and Claudia Vianna, instructors of internal medicine; Jason Anderson, student research assistant in internal medicine; and Dr. Mario Perello, former postdoctoral researcher in internal medicine.

Researchers from the University of Iowa, Harvard Medical School and Brown University/Rhode Island Hospital also contributed to the study, which was funded by the National Institutes of Health and the American Heart Association.


Story Source:

The above story is based on materials provided by UT Southwestern Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

UT Southwestern Medical Center. "Protein must exist in specific brain cells to prevent diet-induced obesity." ScienceDaily. ScienceDaily, 7 July 2010. <www.sciencedaily.com/releases/2010/07/100706123017.htm>.
UT Southwestern Medical Center. (2010, July 7). Protein must exist in specific brain cells to prevent diet-induced obesity. ScienceDaily. Retrieved October 21, 2014 from www.sciencedaily.com/releases/2010/07/100706123017.htm
UT Southwestern Medical Center. "Protein must exist in specific brain cells to prevent diet-induced obesity." ScienceDaily. www.sciencedaily.com/releases/2010/07/100706123017.htm (accessed October 21, 2014).

Share This



More Health & Medicine News

Tuesday, October 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

CDC Revamps Ebola Guidelines After Criticism

CDC Revamps Ebola Guidelines After Criticism

Newsy (Oct. 21, 2014) The Centers for Disease Control and Prevention have issued new protocols for healthcare workers interacting with Ebola patients. Video provided by Newsy
Powered by NewsLook.com
First-Of-Its-Kind Treatment Gives Man Ability To Walk Again

First-Of-Its-Kind Treatment Gives Man Ability To Walk Again

Newsy (Oct. 21, 2014) A medical team has for the first time given a man the ability to walk again after transplanting cells from his brain onto his severed spinal cord. Video provided by Newsy
Powered by NewsLook.com
CDC Issues New Ebola Guidelines for Health Workers

CDC Issues New Ebola Guidelines for Health Workers

Reuters - US Online Video (Oct. 21, 2014) The U.S. Centers for Disease Control and Prevention has set up new guidelines for health workers taking care of patients infected with Ebola. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
'Cadaver Dog' Sniffs out Human Remains

'Cadaver Dog' Sniffs out Human Remains

AP (Oct. 21, 2014) Where's a body buried? Buster's nose can often tell you. He's a cadaver dog, specially trained to find human remains and increasingly being used by law enforcement and accepted in courts. These dogs are helping solve even decades-old mysteries. (Oct. 21) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins