Weight Loss

Being Overweight Can Impact Brain Function

Being overweight can affect your heart, lungs, joints, and cause diabetes and strokes, just to name a few areas of concern. Now we’re learning it can be bad for your brain, too.

Recent research offers a stunning new possibility that brain injury may be a consequence of eating a typical American diet high in fats. “This may explain why losing weight and sustaining that loss is so difficult for most obese individuals to achieve.” said Joshua Thaler, MD, a faculty member with the Diabetes and Obesity Center of Excellence at the University of Washington in Seattle.

Thaler and his colleagues studied the brains of rodents for the short-term and long-term effects of eating a high-fat diet. They gave groups of 6 to 10 rats and mice a high-fat diet for periods from 1 day to 8 months. 

Within the first three days of consuming a diet that had a similar fat content to the typical American diet, rats consumed nearly double their usual daily amount of calories and gained weight throughout the study. It was then found that the rodents developed inflammation in the hypothalamus, the part of the brain containing neurons that control body weight. At the same time, a group of support cells called glia and scavenger cells called microglia accumulated in the hypothalamus and appeared to become activated. Although this collective response to brain inflammation, called gliosis, subsided days later, it recurred after 4 weeks.

Human brain imaging studies in recent years have found that, compared to lean individuals, those who are obese are more likely to have larger populations of these glial cells in the hypothalamus. This same sort of phenomenon, called gliosis, is commonly seen in neurodegenerative diseases, brain trauma, bleeding, infection and brain cancer, leading researchers to initially conclude that dietary excess might essentially cause a form of brain injury. Gliosis is thought to be the brain equivalent of wound healing. It’s believed that this early gliosis may be a protective response that fails over time.

It’s hypothesized that microglia have evolved to rapidly trigger increased appetite and weight gain in response to a high-fat diet. In the past, rich foods were rarely available so it was advantageous to stop hunting or foraging and focus on chowing down for as long as it lasted.

Microglial responsiveness to dietary fats makes some sense from this evolutionary perspective. Fats are the densest form of calories that ancient humans may have had the opportunity to consume. So, when primitive humans finally obtained a meal after a long period of fasting, microglia may have been essential in relaying the presence of the meal to neurons that stimulated a maximal appetite response.

But in modern environments, in which high-fat food is continually available, the same adaptation can be damaging. In our modern world, when people constantly overeat rich, high-fat foods, chronic microglial activation could produce a more permanent stimulation of neural circuits that further increase high-fat food intake, leading to the development of a vicious cycle.

The evidence is growing. Research from the Cambridge Centre for Ageing and Neuroscience found that obese people have less white matter in their brains than their lean peers — as if their brains were 10 years older! Another study from researchers at the University of Arizona supports one of the leading theories, that high body mass is linked to inflammation, which affects the brain.

These experiments also detected damage to, and eventual loss of, critical weight-regulating neurons. The neurons, called pro-opiomelanocortin (POMC) neurons, were reduced in number by month 8 of the high-fat diet in mice. The results were not present in same-age rodents fed standard heathy foods. Mice genetically engineered to prevent microglia from activating inflammatory responses, found that these mice ate 15% less and gained 40% less weight on a high fat diet, suggesting that the inflammatory capacity of microglia itself is responsible for the animals’ overeating and weight gain.

The good news? Once the mice exposed to a typical high fat diet were returned to a healthy diet , the gliosis was reversed. It is therefore speculated that hypothalamic gliosis is reversible in humans as well using diet, lifestyle and other therapeutic options. It is becoming more evident that obesity is associated with brain inflammation, particularly in the hypothalamus where its presence may disrupt body weight control and glucose maintenance. Research may someday be able to provide 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.

Until then, eating healthier with an active lifestyle is a great start to reversing any damage to date.







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