Do hunger hormones make us fat?

Research into the hormones that control our appetite may offer new ways to help fight obesity, according to scientists investigating how the brain helps regulate what we eat.

At 21 stone, Marilyn Walsh felt she had run out of ways to battle her weight and had developed a sense of fatalism about her future.

"My uncle was about 35 stone," she said. "He suffered with weight throughout his whole life - leg problems, stopped walking. He developed diabetes and lots of other problems. And he did die because of his weight."

Given what had happened to her uncle, why was Marilyn, a 38-year-old housewife and mum from London, not able to reduce her weight through dieting?

"It would be a bit like saying: 'Why can't an alcoholic stop drinking?' 'Why can't a smoker stop smoking?' It's exactly the same," she said.

"It's something that's been with me all my life. I'm always hungry, and always wanting food."

Constant craving

Everyone knows what it feels like to be hungry, but to have a constant craving and the inability to feel satisfied in the way that Marilyn described was clearly more unusual.

Image caption Marilyn was 21 stone before the operation

But what is different about people like Marilyn?

Over the past six months, Marilyn has undergone an operation to reduce her weight - an operation which has helped reveal some surprising insights into the mechanisms that control appetite in all of us.

Dr Carel Le Roux, of Imperial College and King's College Hospital in London, studies obesity and the underlying processes that help control the decisions we all make to eat - or overeat.

In 2001, the research unit at Imperial discovered vital clues. They identified two previously unknown hormones called PYY and ghrelin which seem to play a part in our sensations of fullness and hunger.

Ghrelin was linked to the sensation of hunger and PYY to fullness.

"It completely opened up a new chapter," said Dr Le Roux, "because for the first time we understood that the gut can actually talk to the brain and influence how hungry you are, or how full you are."

For many obese patients, Dr Le Roux has found that concentrations of hunger hormones are in many cases significantly different from those in thin people.

Their PYY, which should tell them when to stop eating, is not working properly. Instead their hormones are making them feel permanently hungry - just as Marilyn had described.

Drastic intervention

Last October, Marilyn was admitted to King's College Hospital to undergo a stomach bypass operation. She and her doctors had decided that for a case like hers, surgery might be the only option.

The surgery involved cutting her stomach in two, and connecting only the smaller part to her small intestines. Effectively her stomach was reduced from the size of a fist to the size of a thumb.

It is drastic surgery. She would never be able to eat a full meal again - but it would profoundly affect her weight.

But Dr Le Roux had another motive for performing the operation. According to his research, this operation has a powerful and unexpected side-effect.

As well as reducing her stomach, the operation would also re-balance her hormones.

And for the first time in her life, Marilyn would, in effect, stop thinking like a fat person and think - and behave - like a thin one.

Brain activity

A few weeks after her operation, Marilyn had lost more than four stone. But what seemed just as significant was how her taste had changed.

"I don't like the sweet or the fatty," she said. "The fatty isn't appealing any more.

"And the fat on the roof of your mouth, that was horrible, trying to get rid of that takes a long time."

The change in Marilyn was not unusual, according to Dr Le Roux.

"The patients say: 'Doctor, where did the surgeon do the operation? Did they operate on my tummy or did they operate on my head, because I don't feel hungry any more. When I do eat I feel full and all these changes have really happened in my head.'"

Psychiatrist Dr Samantha Scholtz has been researching how the brain responds to different kinds of food.

Pictures of "healthy" and "unhealthy" foods are shown to patients while an MRI scan measures how the brain reacts.

Obese parents display considerable brain activity, she has found. Stimulated areas of the brain include the orbital frontal cortex, associated with reward, and other areas associated with addiction and an emotional response to food.

But what was surprising was how that response changed in patients who had undergone gastric bypass surgery. Their brain activity totally changed.

"In effect, with bypass surgery we are changing someone's brain fundamentally," said Dr Scholtz.

"Their reaction to seeing high-calorie food is different, and that would ultimately drive their choices of food so that they stop having that battle with food."

Gastric surgery is a drastic intervention - and a controversial one. But Dr Le Roux believes that within a few years it may be possible to engineer a change in the way obese people respond to food in other ways.

"Maybe we can use devices. We can put things into the bowel or we can use injections or pills that actually will do what the operations are achieving. Now if we do that, it opens up the whole science of obesity."

Horizon:The Truth about Fatis on BBC Two at 21:00 GMT on Tuesday 20 March 2012, or watch online afterwards at the above link.

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