Exercise-induced Irisin Hormone May Be Muscle Loss Biomarker

Marta Figueiredo, PhD avatar

by Marta Figueiredo, PhD |

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Blood levels of irisin, an exercise-induced muscle hormone, are significantly lower in people with Charcot-Marie-Tooth disease (CMT) and associate with muscle strength and quality, a small study shows.

The findings suggest that this protein, previously shown to have protective effects against muscle wasting, may be a useful biomarker to monitor muscle mass and strength loss in CMT patients.

More studies are needed to confirm these findings and irisin’s biomarker potential, as well as to assess its role in CMT and whether its administration may be a new therapeutic approach for this patient population, the researchers noted.

The study, “Irisin Serum Levels and Skeletal Muscle Assessment in a Cohort of Charcot-Marie-Tooth Patients,” was published in the journal Frontiers in Endocrinology.

CMT is a group of inherited disorders of the peripheral nervous system, which controls movement and sensation in the limbs, that are characterized mostly by slowly progressive muscle weakness and wasting, sensory problems, and skeletal deformities.

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It is divided into two main types, 1 and 2, based on whether the disease is characterized by progressive loss of myelin, the protective sheath around nerve fibers (CMT type 1), or by nerve fiber degeneration (CMT type 2).

Previous studies in mice suggest that irisin protects against muscle wasting, and human data supports a protective role also against bone fractures.

However, whether irisin could serve as a biomarker of muscle mass and strength in people with CMT is unclear.

To address this, a team of researchers in Italy first analyzed the blood levels of irisin in 20 adults with CMT (12 men and eight women) and 20 healthy people matched for age, sex, and body mass index (BMI, a ratio of weight to height).

Patients’ mean age was 54 years (range, 20–76) and 15 of them (75%) had available genetic data showing that 12 had CMT type 1 and three had type 2 disease.

No patient was taking medication for osteoporosis, had kidney failure, or changed their physical activity and diet at least three months before enrollment — all factors that potentially could influence the results.

Results showed that CMT patients had significantly lower blood irisin levels relative to healthy controls (6.51 vs. 9.34 micrograms per milliliter, or mcg/mL). No significant difference in irisin levels was found between CMT1 and CMT2.

The researchers then assessed potential links between irisin levels and biochemical and muscle parameters in CMT patients.

Biochemical markers were quantified in blood samples, skeletal muscle mass was evaluated by bioelectric impedance analysis (BIA), muscle strength by handgrip, and muscle quality was derived from muscle strength and muscle mass ratio.

BIA is a non-invasive method for measuring body composition based on the rate at which an electrical current travels through the body.

Results showed that skeletal muscle mass in CMT patients was always lower than reference values in healthy Caucasian population matched for age, and muscle quality was lower-than-normal in all but one patient.

When dividing patients based on their muscle strength, the team found that blood irisin levels were significantly lower in those with lower-than-normal muscle strength (nine patients), compared with the 11 patients with normal muscle strength (5.56 vs. 7.67 mcg/mL).

Patients with low muscle strength also had significantly reduced muscle quality, and both irisin and sex were found to be independent predictors of muscle quality, when adjusting for other potential influencing factors.

Notably, while sex differences in terms of irisin levels did not reach statistical significance, they suggested that women had more irisin in circulation. Consistently, higher irisin levels were associated significantly with better muscle strength and quality in female patients only.

However, firm conclusions about a possible sex-specific effect of irisin on muscle health in CMT cannot be drawn due to the small number of included patients, the researchers noted.

In addition, lower blood irisin levels were found to be significantly associated with lower levels of the marker of bone formation P1PN, and higher levels of vitamin D, which has a role in both muscle function and bone health.

Notably, P1PN levels were within the normal range in all patients, but vitamin D levels were below normal in all but one patient.

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These findings “indicate that Irisin correlates with muscle quality and the bone formation marker P1PN in CMT patients and it could represent a new biomarker of the loss of muscle mass and strength,” the researchers wrote.

Larger studies are needed to confirm these findings and better understand the link between irisin and bone and muscle health.

Additional research should also assess whether irisin could represent “a marker of the loss of muscle mass and strength and/or bone loss,” as well as “a new therapy for improving muscle strength and musculoskeletal function in CMT patients,” the team wrote.

“Further studies may uncover a possible involvement of irisin in preventing motor nerve fiber degeneration that occurs in CMT disease,” the researchers concluded.