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Cold-induced endocrine hormones trigger fat cells to turn up the heat

Researchers identify metabolic signaling pathway that may help maintain core temperature

Lowering the thermostat during the winter months could help with the budget – and possibly a more efficient metabolism.

Researchers studying the impact of cold exposure on the human body have identified crosstalk between skeletal muscle and brown fat tissue that is mediated by an exercise-induced hormone. This metabolic signaling may help the body more efficiently maintain its core temperature.

The findings could ultimately be applied to further understand human metabolism and obesity.

Brown adipose tissue is a specialized form of fat tissue that produces heat by burning energy to maintain an organism’s core temperature. In the face of brutally cold conditions, or in the event of hypothermia – the drop of the internal “core” temperature – this becomes an important survival mechanism.

In a study published online Feb. 4in the journal Cell Metabolism, researchers report on an endocrine messaging system between skeletal muscle and brown adipose tissue.

According to lead author Francesco S. Celi, M.D., chair and professor in the Division of Endocrinology and Metabolism at the Virginia Commonwealth University School of Medicine, the contraction of skeletal muscle by exercise or shivering stimulates the release of exercise-induced hormones called irisin and FGF21, which then stimulates brown adipose tissue to produce heat to maintain core temperature.

Celi, who conducted the research at the National Institutes of Health (NIH) while he was staff clinician at the National Institute of Diabetes and Digestive and Kidney Diseases, said the data suggest that in humans the muscle generates not only contraction, but potentially beneficial metabolic signals as well.

“Cold-induced shivering, which is an energy-inefficient mechanism, stimulates the highly efficient brown adipose tissue to maintain the core temperature of the organism,” said Celi.

“From an evolutionary standpoint, this system assures the most efficient means of maintaining core temperature and minimizing the loss of energy stores compared to shivering alone,” he said.

One analogy he uses: the stimulation of brown adipose tissue allows for an upgrade from a space heater to a high efficiency energy star furnace used to warm a house.

According to Celi, the next steps involve the study of long-term effects of brown adipose tissue stimulation by pharmacologic or behavioral intervention. The research will focus on changes in metabolism and the development of potential compensatory mechanisms such as an increase in food intake.

This work was supported by grants from the Intramural Research Program of the NIH. Paul Lee, M.D., Ph.D., the first author of the manuscript, was supported by the Australian National Health Medical Research Council and the Royal Australasian College of Physicians Foundation. The content of this article is the sole responsibility of the study authors and does not necessarily represent the official views of the NIH.

EDITOR’S NOTE: A copy of the study is available for reporters by e-mail request to the Cell Metabolism News Office moleary@cell.com.

 

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An infrared picture of differentiated human adipocytes treated with FNDC5 (a synthetic form of irisin) and FGF21 that produce heat when exposed to norepinephrine, a cold-mimetic. Figure appears in the journal, Cell Metabolism. Figure courtesy of Francesco Celi, M.D./ VCU.
An infrared picture of differentiated human adipocytes treated with FNDC5 (a synthetic form of irisin) and FGF21 that produce heat when exposed to norepinephrine, a cold-mimetic. Figure appears in the journal, Cell Metabolism. Figure courtesy of Francesco Celi, M.D./ VCU.