Abstract
Myotonic dystrophies (DM) are dominantly inherited muscle disorders characterized by myotonia, muscle weakness, and wasting. The reasons for sarcopenia in DMs are uncleared and multiple factors are involved. Irisin, a positive hormone regulator of muscle growth and bone, may play a role. To investigate (1) circulating irisin in a series of DM1 and DM2 male patients compared with healthy controls and (2) the relationships between irisin and anthropometric, metabolic and hormonal parameters. This is a cross-sectional study. Fasting blood samples for glucometabolic, gonadic, bone markers, and irisin were collected from 28 ambulatory DM1, 10 DM2, and 23 age-matched healthy male subjects. Body composition and bone mineralization [bone mineral density (BMD)] were measured by DEXA. Echocardiographic assessment and visceral adiposity, namely, liver and epicardial fat, were investigated by ultrasound. Irisin released from cultured myotubes derived from 3 DM1, 3 DM2, and 3 healthy donors was assayed. Plasma irisin levels were definitely lower in both DM1 and DM2 patients than in controls with no difference between DM1 and DM2. Irisin released from DM1 and DM2 myotubes was similar to that released from myotubes of the non-DM donors, though diabetic DM2 myotubes released more irisin than DM1 myotubes. There was no correlation between irisin and muscle strength or lean mass in both DM1 and DM2 patients. In DM1 patients, plasma irisin levels correlated negatively with oxygen consumption and positively with insulin resistance, while in DM2 patients plasma irisin levels positively correlated with fat mass at arms and legs levels. No correlation with visceral fat, left ventricular mass, and gonadal hormones could be detected. In both DM1 and DM2 patients, legs BMD parameters positively correlated with plasma irisin levels. Plasma irisin is reduced in both DM1 and DM2 male patients likely reflecting muscle mass reduction. Moreover, insulin resistance may contribute to modulation of plasma irisin in DM1 patients. The irisin-mediated cross talk muscle-adipose tissue-bone may be active also in the male myotonic dystrophies' model.
Highlights
Skeletal muscle is emerging as an endocrine organ
Plasma irisin levels detected in patients with DM1 did not differ significantly from levels detected in patients with DM2 [1.1 (1.0–1.5) ng/ml], which were definitely lower than levels detected in controls (Figure 1A)
Irisin released from DM1 myotubes was significantly lower than that released from the DM2 myotubes (0.22 ± 0.07 vs 0.41 ± 0.07 ng/ml; P = 0.03), though they both did not significantly differ from that released from healthy controls myotubes (0.33 ± 0.18 ng/ml; Figure 1B)
Summary
Skeletal muscle is emerging as an endocrine organ. A number of biological active molecules are expressed and released from muscle cells known as myokines [1]. Irisin, the cleaved fragment of the transmembrane protein type-III domain containing protein 5 (FNDC5), was shown to induce adipocyte browning. Irisin acts on subcutaneous adipose tissue increasing thermogenesis and energy expenditure, granting protection against obesity and insulin resistance [2]. Irisin stimulates myogenesis [3]. The circulating 22 kDa form of irisin has been quantitated in human plasma by mass spectrometry [4, 5]. Plasma irisin levels are increased in mice and humans after short-term exercise [6], and it is emerging as a sensitive marker for muscle weakness and atrophy [7]
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