Scientists believe it could be possible to treat obesity by altering levels of fatty acids in a key area of the brain.
Obesity is on the rise across the developed world
They found reducing fatty acid levels in the hypothalamus caused rats to overeat and become obese.
The study, by a team at Albert Einstein College of Medicine in New York, features in Nature Neuroscience.
It suggests that a therapy which restores fatty acid levels in the hypothalamus may be a promising way to treat obesity.
However, UK experts warned that appetite regulation was a complex area.
Obesity is a growing problem across the developed world. In the UK, it is thought that 40% of men, and a third of women are either obese or overweight.
Carrying too much weight is linked to a range of health problems, including a greater risk of heart disease and cancer.
The hypothalamus keeps track of the body's nutritional status by monitoring the blood levels of several different hormones and nutrients.
Taking this information into account, it regulates both appetite, and the speed at which the body breaks down nutrients.
The Einstein team had already shown that glucose is one of the substances closely tracked by the hypothalamus.
Now they have found that fatty acids too are on the organ's checklist.
The researchers focused on a particular fatty acid molecule called malonyl CoA.
They injected a virus on to which was attached an enzyme known to break down malonyl CoA into the hypothalamus of lab rats.
The injections caused a drop in malonyl CoA levels, which led to the rats gorging themselves. The effect lasted for at least four months.
Lead researcher Dr Luciano Rossetti said: "We showed in this study that disrupting malonyl-CoA levels in this region of the brain impairs the nutrient-sensing mechanism by which the hypothalamus modulates food intake to maintain normal weight.
"Figuring out a way to re-adjust malonyl-CoA levels in the human hypothalamus could lead to innovative therapies not only to treat obesity but to help prevent diabetes and other consequences of being overweight."
Dr Ian Campbell, a weight management expert and former chairman of the UK National Obesity Forum, told the BBC News website that research of this kind underlined just what a complex issue obesity was.
"It is not just about greed and laziness," he said.
"There seem to be many underlying physiological factors.
"Clearly we are a long way off being able to prescribe a drug based on this research.
"But work like this does help to increase our understanding of obesity, and does help us work towards new treatments."
Dr Campbell stressed that the best way to combat obesity was to control one's weight through exercise and a sensible diet.
Professor Ian MacDonald, of the University of Nottingham, agreed that it was simplistic to draw too many conclusions from one piece of research.
He said it would be difficult to produce a drug that targeted its effect specifically at the hypothalamus, and that any effect on human appetite that could be produced was likely to be minimal.