High-fat diets affect your brain, not just your physical appearance

September 9, 2019

Science Daily/Yale University

Much research has pointed to how an unhealthy diet correlates to obesity, but has not explored how diet can bring about neurological changes in the brain. A recent Yale study has discovered that high-fat diets contribute to irregularities in the hypothalamus region of the brain, which regulates body weight homeostasis and metabolism.

Led by Sabrina Diano, the Richard Sackler Family Professor of Cellular & Molecular Physiology and professor of neuroscience and comparative medicine, the study evaluated how the consumption of a high-fat diet -- specifically diets that include high amounts of fats and carbohydrates -- stimulates hypothalamic inflammation, a physiological response to obesity and malnutrition.

The researchers reaffirmed that inflammation occurs in the hypothalamus as early as three days after consumption of a high-fat diet, even before the body begins to display signs of obesity. "We were intrigued by the fact that these are very fast changes that occur even before the body weight changes, and we wanted to understand the underlying cellular mechanism," said Diano who is also a member of the Yale Program in Integrative Cell Signaling and Neurobiology of Metabolism.

The researchers observed hypothalamic inflammation in animals on a high fat diet and discovered that changes in physical structure were occurring among the microglial cells of animals. These cells act as the first line of defense in the central nervous system that regulate inflammation. Diano's lab found that the activation of the microglia was due to changes in their mitochondria, organelles that help our bodies derive energy from the food we consume. The mitochondria were substantially smaller in the animals on a high-fat diet. The mitochondria's change in size was due to a protein, Uncoupling Protein 2 (UCP2), which regulates the mitochondria's energy utilization, affecting the hypothalamus' control of energy and glucose homeostasis.

The UCP2-mediated activation of microglia affected neurons in the brain that, when receiving an inflammatory signal due to the high fat diet, stimulated the animals in the high-fat diet group to eat more and become obese. However, when this mechanism was blocked by removing the UCP2 protein from microglia, animals exposed to a high fat diet ate less and were resistant to gain weight.

The study not only illustrates how high-fat diets affect us physically, but conveys how an unhealthy diet can alter our food intake neurologically. "There are specific brain mechanisms that get activated when we expose ourselves to specific type of foods. This is a mechanism that may be important from an evolutionary point of view. However, when food rich in fat and carbs is constantly available it is detrimental."

Diano's long-standing goal is to understand the physiological mechanisms that regulate how much food we consume, and she continues to perform research on how activated microglia can affect various diseases in the brain, including Alzheimer's disease, a neurological disorder that is associated with changes in the brain's microglial cells and has been shown to have higher incidence among obese individuals.

https://www.sciencedaily.com/releases/2019/09/190909121234.htm

Inflammation can lead to circadian sleep disorders

Novel technology turns inflammation on and off, affecting body clock in mice

October 31, 2018

Science Daily/Northwestern University

Inflammation, which is the root cause of autoimmune disorders including arthritis, type 1 diabetes, irritable bowel syndrome and Crohn's disease, has unexpected effects on body clock function and can lead to sleep and shiftwork-type disorders, a new study in mice found.

The study was published in the journal Genes & Development.

The study used a new technology -- a genetic switch -- to turn inflammation on and off in genetically modified mouse models. When researchers deactivated inflammation, the mouse was unable to tell what time it was and was unable to keep an intact rest-activity cycle.

In addition to this new technology, the study was novel because, for the first time, scientists saw a link between what causes inflammation and what controls the body's clock.

In inflammatory diseases, the body experiences an excess of a genetic factor known as NF-kappa beta (NFKB), the study found. NFKB is a catalyst for a set of chain reactions, or pathway, that leads to the pain and tissue destruction patients feel in inflammatory diseases. That same chain-reaction catalyst also controls the body's clock.

"NFKB alters the core processor through which we tell time, and now we know that it is also critical in linking inflammation to rest-activity patterns," said senior author Dr. Joseph Bass, the Charles F. Kettering Professor of Medicine and director of the Center for Diabetes and Metabolism at Northwestern University Feinberg School of Medicine.

When people have sore muscles and take an ibuprofen to reduce the inflammation, they are essentially trying to turn down the activation of inflammation, which is similar to what the authors did in this study, Bass said.

The findings also have implications for diet and provide a detailed roadmap to understanding the fundamental mechanisms by which inflammation -- including the inflammation that occurs when someone chronically consumes a high-fat diet -- and likely other instigators lead to circadian disorders.

The scientists sought to understand how a high-fat diet might affect the perception of time at the tissue level, which is what led to their study of inflammation, said first author Hee-Kyung Hong, research assistant professor of endocrinology at Feinberg.

One of the reasons Western diet contributes to diabetes, cardiovascular disease and even certain cancers is thought to be the inappropriate trigger of inflammation, so a unifying idea is that impaired time-keeping may be one of the links between diet and disease.

"We don't know the reasons, but this interaction between the inflammation and clocks is not only relevant to understanding how inflammation affects the brain and sleep-wake cycle but also how immune or fat cells work," Hong said.

https://www.sciencedaily.com/releases/2018/10/181031124858.htm