High-Fat Diet may Quickly Injure Brain Cells that Control Body Weight

According to the authors of a new study, there may be a neurological reason why it’s so hard for some people to lose weight; obese individuals consuming a high-fat diet may injure neurons in a key part of the brain that control body weight.

"The possibility that brain injury may be a consequence of the overconsumption of a typical American diet offers a new explanation for why sustained weight loss is so difficult for most obese individuals to achieve," said Joshua Thaler, MD, PhD, presenting author and a faculty member with the Diabetes and Obesity Center of Excellence at the University of Washington in Seattle.

Researchers studied the brains of rats and mice, focusing the short-term and long-term effects of consuming a high-fat diet. After administering a high-fat diet to groups of six to ten rodents for periods from one day to eight months, the researchers performed detailed biochemical, imaging, and cell sorting analyses on the brains of the animals.

Thaler reported that within the first three days of eating a diet with similar fat content to the typical American diet, rats consumed nearly double their usual daily amount of calories.

The rats and mice fed the high-fat diet gained a significant amount of weight during the study. Researchers reported that they also developed inflammation in the hypothalamus, the part of the brain holding neurons that control body weight.

Simultaneously, a group of support cells called “glia” and scavenger cells called “microglia” built up in the hypothalamus and appeared to become activated. Although this communal response to brain inflammation—called “gliosis”—subsided days later, it happened again after four weeks.

"Gliosis is thought to be the brain equivalent of wound healing and is typically seen in conditions of neuronal injury, such as stroke and multiple sclerosis," Thaler said. "We speculate that the early gliosis that we saw may be a protective response that fails over time."

Thaler said that researchers also detected damage to—and the eventual loss of—vital weight-regulating neurons.

These neurons, called “pro-opiomelanocortin” (POMC) neurons, were decreased in number after eight months of the high-fat diet in mice, according to Thaler. These results were not present in rodents of the same age in the group fed a regular rodent diet.

It is not yet clear whether this reputed neuronal injury is permanent, but it may contribute to weight gain in humans, Thaler stated.

Thaler continued by saying that this research, funded by the National Institute of Diabetes and Digestive and Kidney Diseases, provides a new potential target for obesity treatment.

"If new medicines can be designed that limit neuron injury during overeating, they may be effective in combating the obesity epidemic," he said.

The results will be presented Tuesday at The Endocrine Society's 93rd Annual Meeting in Boston.