Mice Gut Microbe Study Gives Clues to 'Browning' of White Fat

Veronica Hackethal, MD

November 23, 2015

A study conducted in mice has found that depleting gut microorganisms triggers the browning of white fat and improves glucose control and insulin sensitivity. The work was published online November 16, 2015 in Nature Medicine.

"This study may open novel strategies to target obesity," commented lead author Mirko Trajkovski, PhD, professor at the faculty of medicine department of cell physiology and metabolism at the University of Geneva, Switzerland.

"We suspected that microbiota [all gut microorganisms, most of which are bacteria] could play a role in obesity onset by regulating the balance between white and beige types of fat," he explained.

"Ongoing work aims to identify which particular bacterial species and groups are responsible for [fat] browning and to precisely target those bacteria."

In particular, the study found that gut bacteria help regulate the balance between white and beige fat in mice given therapeutic doses of antibiotics and in mice born and raised in germ-free conditions (germ-free mice), Dr Trajkovski noted.

Depleting gut bacteria in these mice increased the amount of beige fat, which helped to reduce obesity and improve insulin sensitivity.

Can Results Translate to Anything Useful for Humans?

Between 20% of 30% of human body weight is composed of fat, made up mostly of white fat, which stores energy and can contribute to obesity and diabetes.

On the other hand, humans also have brown fat, which is metabolically active and may improve glucose control.

Scientists have recently discovered that "browning" of white fat can occur when cells similar to brown fat, called "beige fat," appear within white fat. Exercise and exposure to cold can induce "browning" of white fat, and the resultant beige fat is metabolically active and can burn fat and glucose to produce heat, Dr Trajkovski explained.

In this study, the researchers fed a high-calorie diet to three groups of animals: normal mice, germ-free mice, and mice given high doses of antibiotics to deplete their gut microorganisms.

The normal mice developed obesity and insulin resistance. Depleting the gut microorganisms in the other two groups of mice, though, protected them against obesity and improved insulin sensitivity and glucose tolerance.

In addition, the germ-free and antibiotic-treated mice showed decreased amounts of white fat as well as increased amounts of brown-fat–specific markers.

And when the researchers repopulated antibiotic-treated mice with gut microorganisms from "normal" mice, glucose tolerance and insulin sensitivity decreased 30 days after treatment. These mice also showed evidence of the reversal of the browning of fat.

But as conventional wisdom holds that killing off gut microorganisms with antibiotics is detrimental to health, this raises the question of how these results might translate to humans, said Dr. Trajkovski.

The answer, he said, may lie in the fact that removal of some specific bacteria — yet to be identified — may induce the browning of white fat.

"Although treating obesity with high doses of antibiotics is unrealistic — mainly due to the risk of antibiotic resistance — we want to explore alternative ways of suppressing or modifying the microbiota and to identify the exact bacteria responsible for this phenomenon," he stressed.

"We would then target for removal only those, while keeping and enriching those bacteria that have a desirable effect on us."

The authors report no relevant financial relationships.

Nature Medicine. Published online November 16, 2015. Abstract

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