Immune cells in brain respond to fat in diet, causing mice to eat

Credit: Martha Sexton/public domain

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 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, without any apparent ill effects.

Furthermore, removing microglia from mice only reduced 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.

UCSF postdoctoral fellow Martin Valdearcos Contreras, PhD, first author on the paper, published in the December 11, 2014 issue of Cell Reports, discovered that when mice consumed large amounts of saturated fats, the fat entered their brains and accumulated in the hypothalamus.

According to the senior scientist for the study, Suneil Koliwad, MD, PhD, an assistant professor of medicine at the UCSF Diabetes Center, the microglia senses the and sends instructions to brain circuits in the hypothalamus. These instructions are important drivers of food intake, he said.

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, according to Koliwad.

Outside the brain—in fat tissue, the liver, and muscles—other immune cells, called macrophages, trigger inflammation in response to "diet-induced obesity," Koliwad said. 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 than macrophages accumulate in peripheral tissues, Koliwad said. But until now, the effects of this microglial build-up were unknown.

"As opposed to classically defined , in which 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," Koliwad 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.

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Journal information: Cell Reports

Citation: Immune cells in brain respond to fat in diet, causing mice to eat (2014, December 12) retrieved 14 October 2019 from
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Dec 12, 2014
Of mice and men:

Detecting Fat Content of Food from a Distance: Olfactory-Based Fat Discrimination in Humans

Excerpt: "The demonstration that humans have a functional olfactory system specific for detecting levels of fat content warrant further explorations into this mechanism given its potential to aid in a general reduction of our fat intake."

But wait, let's find a drug that alters the nutrient-dependent pheromone-controlled hypothalamic GnRH-modulated development of microglia in our brain.

Dec 12, 2014
"Detecting Fat Content of Food from a Distance: Olfactory-Based Fat Discrimination in Humans"

Again you post a link that doesn't support your model.

Dec 13, 2014
No human pheromones have been identified.

"The failure to identify human pheromones has not stopped some enterprising individuals from trying to make a profit from love potions purporting to contain pheromones. In reality, these products often use pig pheromones. "They don't have any history in the biomedical literature—they just fell out of the sky," says olfactory neuroscientist Charles Wysocki, also of Monell. For now, the idea of perfumes and potions based on human pheromonal communication just doesn't pass the sniff test."

Dec 13, 2014
Again you post a link that doesn't support your model.

Everything ever published by serious scientists who understand how RNA-directed DNA methylation and RNA-mediated amino acid substitutions differentiate cell types supports my model.

Nutrient-dependent/pheromone-controlled adaptive evolution: a model.
Kohl JV.
Socioaffect Neurosci Psychol. 2013 Jun 14;3:20553. doi: 10.3402/snp.v3i0.20553. eCollection 2013. Review.

Human pheromones and food odors: epigenetic influences on the socioaffective nature of evolved behaviors.
Kohl JV.
Socioaffect Neurosci Psychol. 2012 Mar 15;2:17338. doi: 10.3402/snp.v2i0.17338. eCollection 2012.

Human pheromones: integrating neuroendocrinology and ethology.
Kohl JV, Atzmueller M, Fink B, Grammer K.
Neuro Endocrinol Lett. 2001 Oct;22(5):309-21. Review.

From fertilization to adult sexual behavior.
Diamond M, Binstock T, Kohl JV.
Horm Behav. 1996 Dec;30(4):333-53.

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