Featured Research

from universities, journals, and other organizations

Weight is a prickly problem: Key role found for hedgehog signaling in controlling fat storage

Date:
January 11, 2010
Source:
Research Institute of Molecular Pathology
Summary:
Obesity is a widespread condition in humans and has many serious consequences. Not only are overweight people faced with surcharges on airplanes but they also have a much higher risk of contracting a number of potentially fatal diseases. A considerable amount of research effort is currently focussed on the problem of weight control but to date genetic screens for factors that cause obesity have been hampered by the lack of an appropriate system.

Obesity is a widespread condition in humans and has many serious consequences. Not only are overweight people faced with surcharges on airplanes but they also have a much higher risk of contracting a number of potentially fatal diseases.
Credit: Image courtesy of Research Institute of Molecular Pathology

Obesity is a widespread condition in humans and has many serious consequences. Not only are overweight people faced with surcharges on airplanes but they also have a much higher risk of contracting a number of potentially fatal diseases. A considerable amount of research effort is currently focussed on the problem of weight control but to date genetic screens for factors that cause obesity have been hampered by the lack of an appropriate system.

Putting it bluntly, yeast do not become overweight. However, fortunately (for us) flies do and this has provided scientists in Josef Penninger's group at the IMBA (Institute of Molecular Biotechnology) in Vienna with a unique handle on the process. Their initial and highly surprising results are reported in the present issue of Cell.

Andrew Pospisilik and Daniel Schramek in Penninger's group have designed a method that allows them rapidly to screen a large percentage of the genome of the fruit fly Drosophila melanogaster for genes that when mutated give rise to disorders in fat metabolism. The screen was based on the extensive fly library at the IMP/IMBA's VDRC (Vienna Drosophila RNAi Centre). Importantly, this permitted them to examine the effects of genes that had previously not been amenable to such studies because mutations in them are lethal at a very early developmental stage. Furthermore, the screen worked in vivo rather than in cultured cells, so there was no need to verify that the results are physiologically relevant.

Application of the screen resulted in a total of about five hundred genes that seemed somehow to be involved in fat metabolism. Many of these had been previously implicated in the process, which confirmed that the method yielded plausible results. Some of the genes identified were found to be active in neurons, suggesting strongly that fat storage in flies can be regulated by neuronal genes: it is clearly the case in mammals that feeding behaviour is under the control of neuronal genes. And some of the candidate regulatory genes worked in muscles: this too is similar to the situation in mammals.

As expected, the majority of hits from the screen related to genes showed to be active in fat tissue. A good number of them were previously unknown and the screen was thus highly successful in pointing out further areas for study. But perhaps the most significant result of the work was the finding that genes associated with the so-called "hedgehog" signalling pathway are involved in the regulation of fat storage. Hedgehog is one of the "pattern" genes in the fly, responsible for ensuring that developing cells assume the correct identity.

The idea that hedgehog also plays a part in controlling fat levels in flies was extremely interesting as it was consistent with previous findings that inhibition of hedgehog signalling protects mice from gaining weight (see Buhman et al. 2004, J. Nutr. 134, 2979-2984). Mammals store fat in so-called adipocytes, or fat cells. Together with Harald Esterbauer at the Medical University of Vienna, and with the expert assistance of Chi-chung Hui at the University of Toronto, Pospisilik was able to show in cultured cells that hedgehog signalling blocked differentiation of pre-adipocytes to white adipocytes.

To examine directly the effects of inhibiting hedgehog signalling in fat tissues, Pospisilik and Esterbauer generated mice in which the Sufu gene was inactivated solely in these tissues. (Sufu is a known inhibitor of hedgehog signalling.) The mice were healthy but noticeably thin and Pospisilik found that this was because they had essentially no white adipose tissue, although their brown adipose tissues levels were unaffected. And in in vitro experiments on pre-adipocytes, hedgehog activation was shown to inhibit expression of a number of pro-adipogenic genes while stimulating expression of anti-adipogenic genes.

Taken together, these results confirm a role in mice -- and thus presumably in man -- for hedgehog signalling in the production of white but not brown adipocytes. Mammals use white adipose tissue as the major storage site for triglycerides, while brown adipose tissue is important in the regulation of body temperature (it metabolizes lipids to generate heat). Inhibiting the storage of fat in white adipose tissue ("bad" fat) could represent a way to control weight gain in humans but any such treatment could be counterproductive if it also affected brown adipose tissue. As Pospisilik says, "Anything that interferes with white fat has generally turned out to have similar effects on brown fat. Hedgehog is one of the first molecules shown to affect white and brown fat differently."

The finding that the hedgehog signalling pathway inhibits the formation of white adipose tissue while leaving brown adipose tissue intact is of enormous potential therapeutic importance. Pospisilik points out that "most overweight people suffer from cold because they have less brown fat and the little they do have is not active." Disrupting the hedgehog signalling pathway in a tissue-specific way (Pospisilik and Esterbauer showed that doing so did not alter glucose tolerance or insulin sensitivity) could channel more fat into brown adipose tissue, thereby helping overweight people both stay warm and lose weight. Perhaps the days of airplace surcharges may finally be numbered?


Story Source:

The above story is based on materials provided by Research Institute of Molecular Pathology. Note: Materials may be edited for content and length.


Journal Reference:

  1. J. Pospisilik, D. Schramek, H. Schnidar, S. Cronin, N. Nehme, X. Zhang, C. Knauf, P. Cani, K. Aumayr, J. Todoric, et al. Drosophila Genome-wide Obesity Screen Reveals Hedgehog as a Determinant of Brown versus White Adipose Cell Fate. Cell, 2010; 140 (1): 148 DOI: 10.1016/j.cell.2009.12.027

Cite This Page:

Research Institute of Molecular Pathology. "Weight is a prickly problem: Key role found for hedgehog signaling in controlling fat storage." ScienceDaily. ScienceDaily, 11 January 2010. <www.sciencedaily.com/releases/2010/01/100109231710.htm>.
Research Institute of Molecular Pathology. (2010, January 11). Weight is a prickly problem: Key role found for hedgehog signaling in controlling fat storage. ScienceDaily. Retrieved September 17, 2014 from www.sciencedaily.com/releases/2010/01/100109231710.htm
Research Institute of Molecular Pathology. "Weight is a prickly problem: Key role found for hedgehog signaling in controlling fat storage." ScienceDaily. www.sciencedaily.com/releases/2010/01/100109231710.htm (accessed September 17, 2014).

Share This



More Health & Medicine News

Wednesday, September 17, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

President To Send 3,000 Military Personnel To Fight Ebola

President To Send 3,000 Military Personnel To Fight Ebola

Newsy (Sep. 16, 2014) President Obama is expected to send 3,000 troops to West Africa as part of the effort to contain Ebola's spread. Video provided by Newsy
Powered by NewsLook.com
Obama Orders Military Response to Ebola

Obama Orders Military Response to Ebola

AP (Sep. 16, 2014) Calling the Ebola outbreak in West Africa a potential threat to global security, President Barack Obama is ordering 3,000 U.S. military personnel to the stricken region amid worries that the outbreak is spiraling out of control. (Sept. 16) Video provided by AP
Powered by NewsLook.com
UN: 20,000 Could Be Infected With Ebola by Year End

UN: 20,000 Could Be Infected With Ebola by Year End

AFP (Sep. 16, 2014) Nearly $1.0 billion dollars is needed to fight the Ebola outbreak raging in west Africa, the United Nations say, warning that 20,000 could be infected by year end. Duration: 00:40 Video provided by AFP
Powered by NewsLook.com
Obama: Ebola Outbreak Threat to Global Security

Obama: Ebola Outbreak Threat to Global Security

AP (Sep. 16, 2014) President Obama is ordering U.S. military personnel to West Africa to deal with the Ebola outbreak, which is he calls a potential threat to global security. (Sept. 16) 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:
from the past week

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