U.S. Department of Health and Human Services

Brain Injury Associated with High-fat Diet and Obesity

In people who are obese, and in rodents fed a high-fat diet, researchers discovered damage to an area of the brain that regulates body weight. Previously, scientists had observed inflammation in the brain of rodents with diet-induced obesity. In the current study, a team of researchers further investigated this adverse process. They began with rats and mice that were particularly genetically susceptible to obesity from a high-fat diet. Within a day on a high-fat diet, the rodents’ brains began to react as if they had suffered serious injury. Genes that promote inflammation were activated, and immune cells called microglia hastened to an area of the brain, the hypothalamus, that controls appetite and body weight. Within 3 days, these microglial cells had increased both in number and size. Within a week, astrocytes—another type of brain cell—had responded as well; the normally discrete projections that branch out from these cells had wrapped into a dense mass. The researchers also observed induction of a protein, Hsp72, known to help protect cells from injury. Although set in motion by a high-fat diet in the present study, these types of brain changes have also been seen in response to brain damage resulting from disruption of blood flow to the brain and even Parkinson’s and Alzheimer’s diseases. Some of the inflammatory and cellular changes were transient at first, as though the brain were attempting to limit adverse effects of the diet, but then reappeared as the high-fat feeding continued; other changes persisted unabated throughout the months of unhealthy eating. Many of the changes began rapidly, even before the animals gained substantial body weight. The researchers then found evidence of brain cell death—specifically of brain cells called POMC neurons, which normally reduce appetite and have other functions that help prevent obesity. With fewer POMC neurons, the likelihood of obesity increases. To see whether similar brain changes occur in people, the researchers analyzed MRI images that had been taken previously. Close inspection of brain images from 34 people revealed differences between lean and obese individuals, with evidence of changes in the hypothalamus of the brain. Thus, this study suggests that obesity and high-fat diet consumption are associated with damage to the brain.

Thaler JP, Yi CX, Schur EA, et al. Obesity is associated with hypothalamic injury in rodents and humans. J Clin Invest 122: 153-162, 2012.