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NIH Research Matters

February 24, 2014

Shivering Triggers Brown Fat to Produce Heat and Burn Calories

Shivering, like exercise, triggers muscles to secrete a hormone that stimulates energy use in brown fat cells. The findings hint at new ways to alter the body’s energy balance and treat conditions such as obesity.

Brown fat tissue in neck area.

PET-CT image showing brown adipose tissue (red). Image by the researchers, courtesy of Cell Metabolism.

During exercise, contracting skeletal muscles release the hormone irisin into circulation. Irisin can induce energy-storing white fat cells to take on characteristics of brown fat (or adipose) cells, which burn energy by generating heat. This muscle-fat crosstalk has intrigued scientists because it’s unclear why muscle tissue, which generates heat when active, would also stimulate fat cells to produce heat.

A team led by Dr. Francesco S. Celi, who is now at the Virginia Commonwealth University School of Medicine, wondered whether cold exposure could also trigger irisin secretion in order to prompt the body to produce heat. The study was conducted at NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), where Celi was staff clinician. Results appeared on February 4, 2014, in Cell Metabolism.

The researchers had 10 people (4 females, average age 27 years) ride a stationary bike. During a brief ride to maximal capacity, irisin levels tended to increase. During a 1-hour ride at an easier level, irisin levels rose about 3-fold, confirming the ability of exercise to increase irisin secretion in humans.

The team next looked at the impact of cold exposure on irisin levels. The participants rested in water-infused thermoblankets that were gradually cooled from 80 to 53°F. The participants’ energy expenditure increased 48%. While their core temperature was maintained, their skin temperature dropped. Measurement of muscle activity via electromyography showed an 88% increase in the 7 participants who shivered and a 13% increase in those who didn’t. Irisin secretion increased proportionally to shivering intensity. The increase was similar in magnitude to the exercise-stimulated secretion.

The team also found that the secretion of fibroblast growth factor 21 (FGF21), a hormone associated with brown fat activation, was affected by exposure to cold.

The researchers next tested human fat cells taken from biopsies of the neck area. This region is rich in “brown-like” or beige cells, which develop within white fat. Treatment with a chemical precursor of irisin and/or FGF21 caused the cells to burn energy, release heat, and adopt molecular characteristics of brown fat cells. These changes were not noted in fat cells taken from other regions of the body that tend to be rich in white fat.

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

Although this was a small clinical study, the findings suggest that exercise-induced irisin secretion could have evolved from shivering-related muscle contraction. The results also suggest that since activation of these pathways results in greater energy expenditure, the pathways may serve as potential therapeutic targets for obesity and related conditions.

—by Carol Torgan, Ph.D.

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Reference: Irisin and FGF21 Are Cold-Induced Endocrine Activators of Brown Fat Function in Humans. Lee P, Linderman JD, Smith S, Brychta RJ, Wang J, Idelson C, Perron RM, Werner CD, Phan GQ, Kammula US, Kebebew E, Pacak K, Chen KY, Celi FS. Cell Metab. 2014 Feb 4;19(2):302-9. doi: 10.1016/j.cmet.2013.12.017. PMID: 24506871.

Funding: NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Australian National Health Medical Research Council; Royal Australasian College of Physicians Foundation; and the School of Medicine, University of Queensland, Australia.

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Editor: Harrison Wein, Ph.D.
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NIH Research Matters is a weekly update of NIH research highlights from the Office of Communications and Public Liaison, Office of the Director, National Institutes of Health.

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This page last reviewed on March 31, 2014

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