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Researchers map how obesity starts and is regulated by the brain.

Immune cells perform a previously unsuspected role in the brain that may contribute to obesity, according to a new study by UC San Francisco researchers.  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 feeding behaviour.

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, 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 opensource study in published in the journal Cell Reports.

The team discovered that when mice consumed large amounts of saturated fats, the fat entered their brains and accumulated in the hypothalamus.  The team state that the microglia sense the saturated fat and send 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 other immune cells called macrophages present in fat tissue, the liver and muscles, 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, the team observed that 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.

The team summise that 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.

Source:  The Regents of the University of California

 

Diets rich in saturated fat produce inflammation, gliosis, and neuronal stress in the mediobasal hypothalamus (MBH). Here, we show that microglia mediate this process and its functional impact. Although microglia and astrocytes accumulate in the MBH of mice fed a diet rich in saturated fatty acids (SFAs), only the microglia undergo inflammatory activation, along with a buildup of hypothalamic SFAs. Enteric gavage specifically with SFAs reproduces microglial activation and neuronal stress in the MBH, and SFA treatment activates murine microglia, but not astrocytes, in culture. Moreover, depleting microglia abrogates SFA-induced inflammation in hypothalamic slices. Remarkably, depleting microglia from the MBH of mice abolishes inflammation and neuronal stress induced by excess SFA consumption, and in this context, microglial depletion enhances leptin signaling and reduces food intake. We thus show that microglia sense SFAs and orchestrate an inflammatory process in the MBH that alters neuronal function when SFA consumption is high.  Microglia Dictate the Impact of Saturated Fat Consumption on Hypothalamic Inflammation and Neuronal Function.  Valdearcos et al 2014.
Diets rich in saturated fat produce inflammation, gliosis, and neuronal stress in the mediobasal hypothalamus (MBH). Here, we show that microglia mediate this process and its functional impact. Although microglia and astrocytes accumulate in the MBH of mice fed a diet rich in saturated fatty acids (SFAs), only the microglia undergo inflammatory activation, along with a buildup of hypothalamic SFAs. Enteric gavage specifically with SFAs reproduces microglial activation and neuronal stress in the MBH, and SFA treatment activates murine microglia, but not astrocytes, in culture. Moreover, depleting microglia abrogates SFA-induced inflammation in hypothalamic slices. Remarkably, depleting microglia from the MBH of mice abolishes inflammation and neuronal stress induced by excess SFA consumption, and in this context, microglial depletion enhances leptin signaling and reduces food intake. We thus show that microglia sense SFAs and orchestrate an inflammatory process in the MBH that alters neuronal function when SFA consumption is high. Microglia Dictate the Impact of Saturated Fat Consumption on Hypothalamic Inflammation and Neuronal Function. Valdearcos et al 2014.

 

 

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