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Gene Manipulated to Fix Obesity 2007-09-04

Posted by clype in Discovery, Health, Science.

A single gene can keep in check the tendency to pile on fat, according to a team of scientists from ‘The University of Texas‘ who have manipulated the gene (called ‘adipose’) to alter the amount of fat tissue laid down by fruit flies, worms and mice.

If the same effect could be achieved in humans, which also carry the gene, it is hoped it could lead to new ways to fight obesity and diabetes.

The study is published in the journal ‘Cell Metabolism’. Lead researcher Mr.Jonathan Graff MD said:

[Picture of Johnathan Graff]
‘From worms to mammals, this gene controls fat formation.

‘It could explain why so many people struggle to lose weight, and suggests an entirely new direction for developing medical treatments that address the current epidemic of diabetes and obesity.

‘Maybe if you could affect this gene, even just a little bit, you might have a beneficial effect on fat.’

The adipose gene was discovered in fat fruit flies more than 50 years ago, but scientists had not pinned down its exact role.

The Texas team used several methods to turn the gene on and off at different stages of the animals’ lives and in various parts of their bodies.

Their work suggested that the gene acts as a high-level master switch that tells the body whether to accumulate or burn fat.

Health impact

Mice with experimentally increased adipose activity ate as much or more than normal mice.

However, they were leaner, had diabetes-resistant fat cells, and were better able to control insulin and blood-sugar metabolism.

In contrast, animals with reduced adipose activity were fatter and less healthy, and had diabetes.

The researchers also showed that gene activity could be turned up or down, not just on or off.

Mr.Graff said this increased the potential to manipulate its effect to treat obesity.

The next step will be to probe further the exact mechanisms by which the gene exerts its control.

Mr.David Haslam MD, clinical director of ‘The National Obesity Forum’, warned that it could take many years to develop genetic treatments for obesity.

In the meantime, he said, the only way to tackle the problem effectively was to encourage people to eat healthily and take exercise.

‘I don’t want patients coming to me saying: “It’s not what I eat, it’s all in my genes”,’ he said.

‘Don’t give my patients another excuse to be victims.’


A protein that guides the early development of creatures as diverse as fruit flies and humans also plays a role in regulating fat and bone formation in adult organisms, researchers at ‘UT Southwestern Medical Center’ have discovered.

The findings, reported in the January issue of the journal ‘Cell Metabolism’, open an avenue for potential therapy in humans for obesity, diabetes, osteoporosis and lipodystrophy, a disorder characterised by a selective loss of body fat.

Mr.Jonathan Graff MD associate professor in ‘The Center for Developmental Biology’, in recent research with the flies found that a protein key to early development also plays a role in fat and bone formation in adult organisms.

he protein, called ‘hedgehog‘, activates a series of biochemical reactions involving a host of other cellular proteins and genes. The complex interaction among these many components is called the ‘hedgehog signaling pathway’ and it is critical that the pathway functions properly in the early stages of development of many organisms. Mutations in proteins that make up hedgehog signaling also are involved in some human cancers and other human diseases.

‘We found that if you stimulate the “hedgehog pathway” in fruit flies, fat formation is blocked and the flies are skinny. If we block the pathway, the flies become obese,’ said Mr.Graff.

‘We also found the same effects in mammalian models, specifically, in mouse cells. Activating the “hedgehog pathway” blocks fat from forming in mammals, while inhibiting the pathway stimulates the creation of more fat cells.”

Mr.Graff and his colleagues also found that the ‘hedgehog signaling pathway’ is altered in the fat tissue of obese mice. That finding might have implications for human health.

‘”Hedgehog” signaling proteins are altered in either genetic obesity or diet-induced obesity, the kinds of obesity that most often affect humans’ Mr.Graff said.

In the obese mice, the researchers found less of the fat-inhibiting components of the ‘hedgehog pathway’.

The scientists who originally discovered the gene that produces the ‘hedgehog protein’ named the gene based on the appearance of fruit flies that lack the gene. Without ‘hedgehog’ signaling, the mutant fly larvae are covered with bristly hairs, and look like little rolled up ‘hedgehogs’.

A series of studies supports the notion that in mammals the hedgehog pathway instructs adult stem cells, telling them what to become.

‘In mammals, it appears that “hedgehog” signaling regulates adult stem cells, diverting them from forming fat cells and redirecting them to become bone’, Mr.Graff said.

‘Unfortunately, as humans age the opposite tends to happen. That is, the amount of bone cells that we have decreases, while the amount of fat cells we have increases.

‘Perhaps as we age, “hedgehog” signals become blocked or decreased. This study implies that if we block “hedgehog” signals, humans would have less bone and more fat. Conversely, if we can activate the pathway, we might be able to prevent or reverse osteoporosis and simultaneously prevent or reduce fat accumulation,’ he said.

Mr.Graff said that other researchers have spent a great deal of effort developing agents to regulate the ‘hedgehog’ pathway. These agents, currently in the early development phase for anti-cancer treatments, hold promise for human use.

‘The drugs already in clinical development might be useful for this purpose as well,’ Mr.Graff said.

‘If medicine could stimulate the hedgehog pathway in adults, those adults could potentially not only get leaner and become more fit, but could also add bone mass as well. That could affect obesity, diabetes, lipodystrophy and osteoporosis, all of which are major human diseases.’

  • Mr.Graff cautioned that because the ‘hedgehog’ pathway is so involved in many biological processes, side effects are possible.

However, agents could be developed to target hedgehog therapies to specific human tissues, such as fat or bone, he said.

‘There are still tremendous hurdles to overcome before a treatment or a drug is developed,’ he said.

‘We have to do the basic research before we even know what those hurdles are.’

The research was funded by the National Institutes of Health, the American Cancer Society and the Leukemia and Lymphoma Society. Media contact: Amanda Siegfried. Tel: 214-648-3404, e-mail: amanda.siegfried@utsouthwestern.edu



1. Bruno Feikles - 2012-11-13

There is always in increasing trend in obesity these days as more and more people turn into a sedentary lifestyle..

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