Over most of the course of human history, being fat has been good. Fat insulates us from cold winters and acts as a buffer against starvation. Our brains are happiest when we are a little tubby.
When we diet, our brains become very unhappy indeed.
The empty stomach starts to pump the appetite hormone ghrelin into the blood, clouding our minds with hunger. Go on a prolonged diet and AgRP neurons in the hypothalamus, specially designed to sense hunger, switch into starvation mode.
A body functioning normally will build and burn fat throughout the day to keep our energy levels balanced; in starvation mode the body will grab any spare energy it can get to build fat.
“If you go off your diet for just a couple of days, those neurons have tuned the body to use only carbohydrates and store the fat on the body,” says Dr Andrews.
“That, we think, is why it’s so hard to keep weight off after a diet – you’re fighting against your body’s natural desire to put on fat.”
In work published in Cell Reports on Wednesday, Dr Andrews’ team showed that if the switch can be flicked on, it can also be flicked off.
The team used mice genetically modified to lack an important enzyme, Crat. This molecular switch tells AgRP neurons to put the body into starvation mode.
The modified mice were put on a short fast. Normally, this would make their brains switch their fat burners off, leading to increased weight gain when they came off the fast – yo-yo dieting.
But the mice without the enzyme did not enter starvation mode, and continued to burn fat when they resumed a normal diet.
“This offers the opportunity to trick the brain and not replace the lost weight,” Dr Andrews says.
A second study, from a team at St Vincent’s Institute of Medical Research, demonstrates a similar trick using the hormone ghrelin.
Dr Sandra Galic and her team genetically modified mice to lack an enzyme that responds to ghrelin.
In a paper published on Tuesday, the team showed that by blocking the ghrelin receptor, the signal to eat after dieting was blocked, keeping the mice lean.
Together, the two papers offer interesting new targets for drugs that could switch off starvation mode – or switch off our appetite altogether.
Both trials were on mice, and it is relatively rare for animal studies to translate directly into humans, cautioned Dr Keiron Rooney, an obesity researcher at The University of Sydney.
“And anyway, do we even want to be controlling our appetite with a drug? Are we happy to outsource an innate behaviour to a pill?”
Liam is Fairfax Media’s science reporter
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