Ancient lean gene

University of Texas: 4-Sep-2007 12:00 Eastern US Time

Scientists have found a gene that seems to have been keeping creatures lean since ancient times.

The gene was first discovered in flies by another research team. But it also keeps worms and mice trim, according to a report in the September issue of Cell Metabolism.

If the gene works the same way in humans, the discovery could lead to a new weapon against our bulging waistlines.

The gene is called Adipose (Adp). Animals without a working copy of it become obese. Those with greater than normal Adp activity in their fat tissues become slimmer, the researchers found.

"Maybe if you could affect this gene, even just a little bit, you might have a beneficial effect on fat," said Jonathan Graff of the University of Texas Southwestern Medical Center. He points out that people often become overweight very gradually, adding just one or two pounds a year.

"After 30 years, that's a lot."

Worms and flies are routinely studied as models of human health and disease. But that has been less true in fat biology, Graff says.

That's because worms and flies store their fat in multi-functional cells. Mammals on the other hand have special-purpose fat cells, known as adipocytes. But that difference doesn't rule out the possibility that the animals might use similar genes to control fat storage, Graff says.

In the new study, his team found that worms lacking Adp activity got fat. They seemed otherwise quite healthy and fertile. The scientists searched the genetic database in search of related genes. They finally found one that was very similar in flies.

Indeed, another scientist Winifred Doane, had found a natural strain of plump flies in Nigeria almost 50 years ago. These fat flies carried a mutation in their Adp gene.

The flies lived in a climate marked by cycles of famine. This meant they probably benefited from being highly efficient at fat storage, Doane had suggested.

To explore Adp further, Graff and his colleagues produced a strain of mutant flies like those that Doane had found years earlier. They found that the mutant flies were fat and had trouble getting around.

Flies with only one copy of the Adp mutation fell somewhere in between the fat and normal flies. This was evidence that the gene's effects are 'dose-dependent'.

This is good news for possible treatments for human obesity, Graff says. "Because it's like a volume control instead of a light switch. It can be turned up or down, not just on or off. Eventually, of course, the idea is to develop drugs to target this system, but that's in the years to come."

Turning now to mammals - and mice in particular - the researchers found the same kind of patterns.

"We made mice that expressed Adp in fat-storing tissues, and lo and behold, what happened," Graff said. "They were skinny. They weighed less, with markedly less fat. And their fat cells were smaller."

Smaller fat cells usually means better metabolic function, he said, including better blood sugar control.

Storing fat is a good way to get through lean times but too much fat in times of plenty causes health problems.

The search for molecules in the body that cause weight gain and poor blood sugar control "has taken on additional urgency due to the recent dramatic increase in obesity and diabetes," Graff said.

But in the modern world where many people have more or less unlimited supplies of food, it's a wonder that even more people aren't overweight, he added. Perhaps Adp is the answer.

If the gene plays a similar role in humans "it may be that some people's Adp works very well."

More help with words

breed

cell

conception

DNA

fertilisation

inherit

protein

species

sperm

What's it all about?

1. The gene this story is about was first discovered in -----?
2. What does the gene do?
3. The scientists in the story have been studying the same gene in two different types of creature. Name one of them.
4. Do we know yet if the gene does the same thing in humans?
5. What happens to flies, mice and worms that do not have the Adipose gene?
6. What happens to flies, mice and worms that that have plenty of Adipose activity in their body fat?
7. Do people usually put weight on suddenly?
8. What word in the story gave you the answer to that last question?
9. Worms and flies are often studied to learn more about health and disease in the human body – but not usually by scientists interested in ---.
10. That’s because worms and flies on the one hand and humans on the other have quite --------- kinds of fat cells.
11. But scientists might be able to learn something about fat in humans by studying worms and mice. That’s because although the cells might be different the ----- might be similar.
12. Graff and his colleagues studied a gene that helped keep worms slim first. What did they do next?
13. What did they find?
14. The flies that Doane had studied were fat because their Adp gene did not work normally. What word is used in the story to say this?
15. Why would Doane’s flies have found it useful to be able to store fat well?
16. Genes almost always come in pairs. When Graff and his colleagues produced flies with just one Adp gene that worked normally and one that didn’t what were the flies like?
17. What was this evidence for?
18. In one sentence and your own words explain why we would want a “volume control instead of a light switch” in a treatment for human obesity.
19. The scientists found the same type of results in their experiments with mice. Thinking back to what we were told about fat cells in different animals near the start of the story, why did the scientists do experiments on mice as well as on flies?
20. Getting fat is a big problem for many of us. So why do our bodies store fat at all?
21. In countries like ours, in which many people can eat as much as they want, it is surprising that more people are not fat. What does Graff suggest is the reason for this?

More science teaching resources for this story

Lean gene UK US

Topic for discussion, research or pupil presentations

Have the students look at the fat mice created by scientists here and here. Then in groups get them to discuss if it is ethical to do this kind of thing to animals.

Ask the question in different ways with different groups without letting the other groups see the wording. For example:

"Is it ethical to inflict suffering and death on animals in the hope of helping people who stuff themselves?"

"Is it ethical to experiment on animals with the aim of finding a cure for people who eat too much?"

"Is it ethical to use animal models to find cures for humans diseases such as diabetes and obesity?"

Get each group to prepare a PowerPoint presentation to deliver in turn to the class.

Discuss the results as a whole class. What can we learn from this exercise?

Tips for science class discussions and groupwork

No 61

Ground rules for discussion

You, as the teacher, will need to establish rules or guidelines on appropriate and inappropriate modes of argument and self-expression. The goal is a general atmosphere of mutual respect and tolerance but is more readily stated than achieved.

In defining the rules or framework for discussion, attention should be paid to both cultural and religious sensitivity as well as maintaining a balance between objectivity and emotional engagement. Try not to allow students to personalise the issues under discussion as this may arouse feelings of guilt and a need for self-justification.

Multiple perspectives can arise from differences of culture, religion, social class, gender or academic discipline and when several students within the group share a perspective the discussion can break down into a contest between rival ‘factions’.

A clear framework suggested by Susan Illingworth for students in Higher Education can be helpful here. Teachers should ensure that:

* Every member of the group has an opportunity to speak.

* Views can be expressed without interruption.

* Criticisms are aimed at arguments and not individuals.

* There are mechanisms for defusing heated situations.

* Participants are encouraged to apply constructive criticism to their own beliefs

* Participants are encouraged to look for common ground between opposing views

* Teaching materials are selected for their accessibility to a range of viewpoints.

Students are used to being asked for the correct answer, it will take them a while to come to terms with the fact that when discussing bioethics there will not always be correct answer, this needs to be made clear to them.

Students should feel safe in the classroom environment. As private individuals they could refuse to participate in a debate if it distressed them either by remaining silent or by walking away but in school students are expected to remain in class.

From section on Working with discussion at BioEthics Education Project