Exercise-induced hormone irisin linked to new mechanisms for bone metabolism

March 03, 2017

BOSTON (March 3, 2017)--Two weeks of voluntary wheel running induces higher expression of irisin--a fat-burning hormone that is released during exercise--in bone tissue in mice. In addition, systemic administration of irisin increased bone formation and thickness, mimicking the effects of exercise on the mouse skeletal system. The findings demonstrate a potential new mechanism for the regulation of bone metabolism.

The study was led by scientists from Tufts University School of Dental Medicine (TUSDM) and published in Bone Research.

"Our results provide insight into the complex regulatory interplay of muscle, bone and fat tissues. Increased irisin levels in circulation upon systemic administration can recapitulate part of the beneficial effects of exercise in the skeletal system," said senior study author Jake Chen, D.M.D., M.D.S., Ph.D., professor and biological sciences researcher at TUSDM. "Further experimentation will be needed to evaluate the involvement of irisin and other factors increased by exercise and expressed by bone, muscle and fat tissue."

Previous studies have revealed that exercise induces the production of irisin and its precursor molecule, FNDC5 (fibronectin-type III domain-containing 5) protein, which convert white fat tissue into beneficial, calorie-burning brown fat. Irisin has been linked to improved glucose tolerance and weight loss in obese, prediabetic mice. While most studies have focused on irisin produced by muscle tissue, some research has suggested that irisin increases bone mass in addition to its metabolic benefits. However, it was unknown whether irisin is secreted by bone upon exercise or whether it regulates bone metabolism.

To investigate, Chen and his colleagues tested a group of five-week-old mice, with two weeks of voluntary wheel running. Compared to a control group without access to a running wheel, mice that had exercised expressed six-fold higher FNDC5 and irisin expression in bone tissue. Irisin expression was observed in several different bone regions, including the growth plate, trabecular bone, cortical bone, articular cartilage and muscle-bone interface.

When mice were injected with irisin or viruses engineered to express irisin, the team found significant increases in bone volume and thickness compared to mice treated with saline. The team evaluated the effects of recombinant irisin in bone cell lines, and found that irisin can directly increase the production of osteoblasts--cells that synthesize bone--and mineralization, while inhibiting the production of osteoclasts--cells that break down bone.

The team's findings demonstrate that irisin produced by bone could have a role in bone metabolism through both direct mechanisms and indirect mechanisms, as the transition from white fat to brown fat has been shown to lead to increased bone formation by previous studies. In addition, recombinant irisin has also been shown to suppress sclerostin, a protein that is involved in bone loss during prolonged lack of mechanical load, such as in bed-ridden patients.

"Exercise-induced irisin may not only act as an endocrine factor capable of promoting the browning of white adipose tissue, but could also regulate bone metabolism by autocrine mechanisms," said Chen, who also serves as faculty in the Cell, Molecular & Developmental Biology program at the Sackler School of Graduate Biomedical Sciences at Tufts. "Our results suggest that irisin may have a therapeutic potential in strengthening bone in bone-loss-associated diseases, and additional studies are needed to evaluate the underlying mechanisms by which irisin functions."
-end-
Additional authors on the study are Jin Zhang, Xiaofang Zhu, Dana Murray, Yuwei Wu, Liming Yu, Hua Jiang and Qisheng Tu of the Division of Oral Biology, Department of Periodontology at TUSDM, Jin Huang and Zhiwei Xu of Guangzhou University of Chinese Medicine (GZUCM), Paloma Valverde formerly of Wentworth Institute of Technology and Michel Dard of the New York University College of Dentistry. Jin Zhang, first author, is also affiliated with GZUCM. Co-corresponding author is Qisheng Tu.

This work was supported by the National Institute of Dental and Craniofacial Research (award DE021464) of the National Institutes of Health, an Innovation in Oral Care Award through the International Association for Dental Research and GlaxoSmithKline Consumer Healthcare, International Team of Implantology, and the GZUCM Science Fund for Creative Research Groups and GZUCM Torch Program.

Zhang et al. "Exercise-induced irisin in bone and systemic irisin administration reveal new regulatory mechanisms of bone metabolism." Bone Research (2017). Article number: 16056 (2017) DOI:10.1038/boneres.2016.56.

About Tufts University School of Dental Medicine


Founded in 1868, Tufts University School of Dental Medicine (TUSDM) is committed to leadership in education, patient care, research, and community service. Students obtain an interdisciplinary education, integrated with medicine, with access to training in dental specialties. Clinics managed at TUSDM provide quality comprehensive care to more than 18,000 diverse individuals annually, including those with special needs. Nationally and internationally, the School promotes health and educational programs and researches new procedures, materials and technologies to improve oral health.

Tufts University, Health Sciences Campus

Related Brown Fat Articles from Brightsurf:

Transplanted brown-fat-like cells hold promise for obesity and diabetes
A potential therapy for obesity would transplant HUMBLE (human brown-like) fat cells, human white fat cells that have been genetically modified using CRISPR to become similar to heat-generating brown fat cells.

Scientists discover the switch that makes human brown fat burn energy
The receptor responsible for activating the energy-burning property of brown fat in humans has been identified.

Fat check: Yale researchers find explanation for stress' damage in brown fat
In their search for what triggers the damaging side-effects caused by acute psychological stress, Yale researchers found an answer by doing a fat check.

People with brown fat may burn 15% more calories
Short-term cold exposure may help people with brown fat burn 15% more calories than those without, according to a small study published in the Endocrine Society's Journal of Clinical Endocrinology & Metabolism.

Brown fat can burn energy in an unexpected way
Researchers in the lab of Joslin's Yu-Hua Tseng, PhD, a Senior Investigator in the Section on Integrative Physiology and Metabolism at Joslin Diabetes Center, have discovered an unexpected biological pathway by which brown fat cells can translate energy into heat.

The leptin activator: New study reveals brain receptor key to burning brown fat
In a new study published in Nature Communications, Michigan researchers reveal a pathway by which the hormone leptin contributes to weight loss.

New mechanism underlying organelle communication revealed in brown fat cells
A new study reveals an underappreciated interplay between the endoplasmic reticulum and the mitochondria with implications for weight loss and disease.

Gene network helps to turn white fat into beneficial calorie-burning fat
1.9 billion people in the world are overweight. Of these, 650 million people are obese, which increases the risk of secondary diseases such as cancer.

Brown and white body fat speak different languages
Most adults have two types of body fat: white and brown.

Scientists discover why brown fat is good for people's health
Rutgers and other scientists have discovered how brown fat, also known as brown adipose tissue, may help protect against obesity and diabetes.

Read More: Brown Fat News and Brown Fat Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.