Keeping pounds off long-term is difficult for even the most successful dieter, and scientists may now be on the path to determining why.

A study published recently in The Journal of Clinical Investigation shows that high-fat foods cause damage to the hypothalamus - an area in the brain responsible for hunger, thirst and the body's natural rhythms and cycles - in rodents.

“These are really important papers that begin to push the idea out that we’re not in control as much as we think we are,” says Dr. Steven R. Smith, co-director for the Sanford-Burnham Diabetes and Obesity Research Center, who wasn’t involved with the study.

However, Smith says researchers must first determine if the scarring happening in the rodent models will translate to the human condition. Not everything that scientists observe in rodents also applies to humans, of course, but it is a starting point.

“This is the tip of the spear. We’ve been talking a lot about diet and willpower and exercise and this sort of thing. This is radically different [thinking] - that diets can actually re-program the structure of the brain.”



The human body is designed to regulate how much fuel is stored as fat through a process called energy homeostasis, the study's lead author Dr. Michael Schwartz says. For a normal-weight person, that's good. But once a person becomes obese, his or her body seems to want to stay at that new weight permanently.

"That's the biggest problem with obesity treatment," says Schwartz, director of the Diabetes and Obesity Center of Excellence at the University of Washington. "Obese people can lose weight, but they have trouble keeping it off."

Schwartz and his team found evidence of inflammation, or neuron injury, in rats and mice only three days after the rodents consumed foods high in fat. Although the effect subsided temporarily, a long-term diet of unhealthy fare left permanent damage. Schwartz believes the brain's attempt to heal the injured neurons results in gliosis, a process that leads to scarring in the central nervous system.

The researchers also found a 25% reduction in the number of POMC cells in the rodents on a high-fat diet. POMC cells play a critical role in the body's fat control system, helping regulate appetite and prevent excess weight gain.

"Losing those cells would help explain why a new elevated level of body weight would occur," Schwartz says.

Smith says that the study is the result of more than a decade of hard work from neuro-scientists around the world who are trying to understand the body’s weight loss system.

“It may be a little bit more complicated than how hard we try and what we food we eat,” Smith says. “I don’t know if that makes people feel better or worse, but it gets us out of the blame game.”

He believes this study represents a step in the right direction for obesity treatment.

“Let’s say we could get the wiring straight again and we could reverse some of this gliosis [scarring],” Smith says. “What if we could get the wires to work right again, and make it easier to lose weight? I think that’s really an exciting idea.”

Schwartz’s team analyzed human MRIs during their study, discovering higher levels of gliosis in obese patients. The findings suggest the structural damage occurring in the rodents' brains may be duplicated in humans.

"Most wonder, 'Why can't I keep the weight off?'" Schwartz says. "Trying to come up with an explanation for it has been a challenge. This may be putting us on the path to understanding better why it's so hard."