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High fat diet leads to brain inflammation and obesity

brain_on_fire

The stomach strikes again, or so it seems. We’ve already covered how your stomach seemingly controls your brain and your blood-brain barrier, but now it seems that what you eat –not too indirectly related to your stomach– might make you fatter, but not in the way you might be thinking thinking. What you are eating may be causing inflammation in the brain.

When the researchers fed mice a diet high in saturated milk fats, microglia, a type of immune cell, underwent a population explosion in the brain region called the hypothalamus, which is responsible for, you may have guessed it already, feeding behavior.

The researchers used an experimental drug and, alternatively, a genetic approach to knock out these microglia, and both strategies resulted in a complete loss of microglia-driven inflammation in the hypothalamus. Remarkably, doing so also resulted in the mice eating less food each day than did their untreated counterparts — more importantly, without any apparent ill effects.

Furthermore, removing microglia from mice only reduced food intake when the content of saturated fat from milk in their diets was high. It had no effect on mice fed a low-fat diet, or a diet high in other types of fat, including olive oil or coconut oil.

The team discovered that when mice consumed large amounts of saturated fats, the fat entered their brains and accumulated in the hypothalamus.

According to the researchers  the microglia senses the saturated fat and sends instructions to brain circuits in the hypothalamus. These instructions are important drivers of food intake.

Microglia are primarily known for causing inflammation in the brain in response to infection or injury, but the new study indicates that they also play a key role in shaping the brain’s response to diet.

Outside the brain—in fat tissue, the liver, and muscles—other immune cells, called macrophages, trigger inflammation in response to “diet-induced obesity.” This inflammation is implicated in triggering insulin resistance, a late stage event on the road to type 2 diabetes.

However, overeating causes microglia to accumulate much more quickly in the hypothalamus than macrophages accumulate in peripheral tissues. But until now, the effects of this microglial build-up were unknown.

“As opposed to classically defined inflammation, in which immune cells build up in tissues where environmental insults have created disarray, microglial activation in the brain may be a part of a normal physiological process to remodel brain function in response to changes in the composition of food intake,” Suneil Koliwad, MD, PhD, senior scientist said.

“When the intake of saturated fats is chronically high, this microglial sensory network may be hijacked, and this has the potential to mediate increased food consumption and promote more rapid weight gain.”

“Targeting microglia may therefore be a novel way to control food intake in the face of consumption of a fat-rich diet, something that is quite common in today’s world,” he said.

As with any big study, more work needs to be done and long term studies will be needed to determine what effects, if any, treatment might have.

As it turns out the old saying, “You are what you eat” might actually hold more credence than even the person who coined the phrase could know.

Sources
Valdearcos, M., Robblee, M., Benjamin, D., Nomura, D., Xu, A., & Koliwad, S. (2014). Microglia Dictate the Impact of Saturated Fat Consumption on Hypothalamic Inflammation and Neuronal Function Cell Reports DOI: 10.1016/j.celrep.2014.11.018

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