Obesity lessons learned from rats diving into cheesecake

Prof Paul Kenny has a strong aversion to cheesecake. When you’ve seen a rat dive head first into a slice and gorge so vigorously that it covers its fur in blobs, chances are you won’t be ordering a portion anytime soon. “It’s not pleasant,” the professor says, in what I’m guessing is a large understatement.

The 41 year-old scientist from Finglas in Dublin feeds cheesecake to rats in a Manhattan lab in a set of experiments that has turned him into a world expert on food addiction. His work on the effect of a cheesecake diet on the brains of the lab rats featured on a recent BBC Horizon programme investigating which is worse for humans: a diet of fat or a diet of sugar. The Irish scientist's research suggests that the combination of both is so addictive it could lie at the heart of the obesity epidemic.

The animals featured on the BBC were not his rats, he explains. They don’t allow cameras to film in the lab. The two stunt rats, (including a hairless rat which “scared the bejaysus” out of him) were filmed nibbling gently on their pieces of cheesecake in a glass case as Kenny explained his research on camera. He hadn’t seen the programme when we spoke. But a few seconds of that hairless rat was all the cheesecake-aversion therapy any viewer could need.

Those animals were newly introduced to the food, Kenny explains. Given a bit more exposure they would have been cheesecake-diving like the ones he has witnessed in the lab.

As a child in primary school in Finglas, Kenny was always fascinated by the science of the brain. He studied biochemistry at Trinity College Dublin, where work in Prof Keith Tipton's lab got him started looking at enzyme activity or the biology of our brains.

He completed a doctorate in neuropharmacology at Kings College in London, and got his first job in the Scripps Research Institute in California. Food was not on his radar at first. His area of interest was the brain’s relationship to drug addiction.

In 2010 his research into the overlap between the brain’s response to drugs and food resulted in an explosion of headlines. The US media seized on the idea of junk-food junkies with cupcakes compared to cocaine in addictive behaviour patterns. Kenny’s three-year rat study had found that hedonic eating (consuming food for pleasure rather than hunger) had a similar impact on the brains of the rats as the consumption of drugs.

Kenny has moved from California to New York, where he is head of the pharmacology and systems therapeutics school in Manhattan’s Mount Sinai Hospital.

The Upper East Side hospital is an “incredibly invigorating” environment for a scientist, he says. That sense of being at the cutting edge of research makes “you feel like you’re being pushed”.

Brain pathways
The race to understand how our brains work has massive potential for pharmaceutical companies to turn academic research into medicine targeting the brain pathways that lead to destructive behaviour like addiction.

Neuroscience has undergone a “revolution” in the past five to 10 years, Kenny believes. Brain-imaging technology is much more advanced, genetics research and the ability to study small areas of the brain to understand why they do what they do are creating a neuroscience renaissance.

Recently scientists were able to isolate a protein in one brain circuit that undergoes a genetic change in tobacco-dependent smokers, he says. This makes sense of “the weird disconnect between smokers who really want to quit and simply can’t”.

Kenny's original research in nature neuroscience (with its less headline-friendly title Addiction-Like Reward Dysfunction and Compulsive Eating in Obese Rats ) found a clear overlap between obesity and drug addiction. The effects on the brain of feeding an animal cocaine and feeding them cheesecake were startlingly similar. "Eventually your body adjusts to them. It's exactly the same process," he says.

Our ideas about drug withdrawal rely heavily on films like Trainspotting which emphasise the physical side-effects. But the real heart of withdrawal is emotional, Kenny explains. "There's an extreme misery to withdrawal."

And this emotional reaction is harder to withstand than the physical symptoms. The reason for this, Kenny explains, is that the brain has adjusted its own pleasure gauge downwards, taking pleasure away from everything else except the drug. The effects of high-pleasure foods had a similar impact. After weeks of cheesecake, carrot sticks just don’t appeal.

“Your brain adapts the same way to these high-pleasure foods. Take the food away and you do feel miserable. So if you’ve eaten a McDonald’s meal every day and then change to a healthy salad it doesn’t do it.”

It’s those brain pathways, the pleasure centres that light up when we eat certain foods or use certain drugs, that cause most people who lose weight to relapse, he says.

Kenny’s research has highlighted for him “that food is not as innocuous as you would think it could be” .

That initial research was simple. Rats were given sugary diets while others were given fat. Neither group of rats gained much weight on either diet. But when fat and sugar were combined the reaction of the animals was completely different.

The rats would nibble tentatively at the new food and then, when they were used to it, they would binge on it. After the binge phase finished, they continued to graze on the food, constantly eating it, he says, as if the off-switch telling them they were full had malfunctioned. “It completely changed them.” They stopped exercising and gained massive amounts of weight.

A rat on a fat-only diet might take 40 to 50 days to gain a small amount of weight. The cheesecake rats gained serious weight after seven days.

The next stage of Kenny’s research is to look at animals who have been on the cheesecake diet for a long time and how they react when the food is taken away and healthy food is put back into the cages. So far they’ve found “they completely reject that food. The animals would rather starve themselves.”

His rats will also withstand mild electric shocks to eat junk food, showing that the eating has become compulsive.

“It’s something that, as humans, we’ve all known. Certain blends of foods taste great.” And the overeating rats very quickly grew to “detest regular food. They just won’t eat it.”

A food becomes addictive, Kenny believes, if “much like tobacco addiction you ask can the substance cause problems and do people have difficulty controlling the use of that product” .

The fact that the rats took electric shocks to get to their food has a parallel in human behaviour. And it is this compulsion that Kenny is interested in exploring.

“Why you put so much value on the stuff that you like to eat that you’re willing to risk a lot,” including health, the ability to find a partner, even longevity. “Why give up so much to continue with your current diet. Which brain systems are at work?”

His latest research involves working with a UK expert on the gene that controls body weight. At some point he and other scientists might isolate a therapy to reverse damaging brain impulses that cause us to do things that are bad for us. In the meantime if you want to cut cheesecake consumption visit, on YouTube, BBC's Horizon Sugar v Fat . That hairless rat appears just over 48 minutes in.