Endocrinol Metab.  2021 Oct;36(5):1055-1068. 10.3803/EnM.2021.1104.

Musclin Is Related to Insulin Resistance and Body Composition, but Not to Body Mass Index or Cardiorespiratory Capacity in Adults

• Sánchez YL
• Yepes-Calderón M
• Valbuena L
• Milán AF
• Trillos-Almanza MC
• Granados S
• Peña M
• Estrada-Castrillón M
• Aristizábal JC
• Narvez-Sanchez R
• Gallo-Villegas J
• Calderón JC

• KMID: 2521953
• DOI: http://doi.org/10.3803/EnM.2021.1104

Abstract

Background
We studied whether musclin function in humans is related to glycemic control, body composition, and cardiorespiratory capacity.
Methods
A cross-sectional study was performed in sedentary adults with or without metabolic syndrome (MS). Serum musclin was measured by enzyme-linked immunosorbent assay. Insulin resistance (IR) was evaluated by the homeostatic model assessment (HOMA-IR). Body composition was determined by dual-energy X-ray absorptiometry and muscle composition by measuring carnosine in the thigh, a surrogate of fiber types, through proton magnetic resonance spectroscopy. Cardiorespiratory capacity was assessed through direct ergospirometry.
Results
The control (n=29) and MS (n=61) groups were comparable in age (51.5±6.5 years old vs. 50.7±6.1 years old), sex (72.4% vs. 70.5% women), total lean mass (58.5%±7.4% vs. 57.3%±6.8%), and peak oxygen consumption (VO_peak) (31.0±5.8 mL O2./kg.min vs. 29.2±6.3 mL O2/kg.min). Individuals with MS had higher body mass index (BMI) (30.6±4.0 kg/m² vs. 27.4± 3.6 kg/m²), HOMA-IR (3.5 [95% confidence interval, CI, 2.9 to 4.6] vs. 1.7 [95% CI, 1.1 to 2.0]), and musclin (206.7 pg/mL [95% CI, 122.7 to 387.8] vs. 111.1 pg/mL [95% CI, 63.2 to 218.5]) values than controls (P˂0.05). Musclin showed a significant relationship with HOMA-IR (β=0.23; 95% CI, 0.12 to 0.33; P˂0.01), but not with VO_peak, in multiple linear regression models adjusted for age, sex, fat mass, lean mass, and physical activity. Musclin was significantly associated with insulin, glycemia, visceral fat, and regional muscle mass, but not with BMI, VCO2peak, maximum heart rate, maximum time of work, or carnosine.
Conclusion
In humans, musclin positively correlates with insulinemia, IR, and a body composition profile with high visceral adiposity and lean mass, but low body fat percentage. Musclin is not related to BMI or cardiorespiratory capacity.

Keyword

Hormones; Musclin protein; human (OSTN); Metabolic syndrome; Insulin resistance; Muscle; skeletal; Body composition

Figure

• 

  Fig. 1 Schematic representation of the study protocol. Participants were interviewed by two physicians and a complete medical history was recorded (1). If the participants did not meet any exclusion criteria, they were then scheduled for biochemical tests, including serum samples for musclin, all under fasting conditions (2). After being classified as with or without metabolic syndrome (MS) according to clinical and biochemical criteria, the participants underwent direct ergospirometry to evaluate their cardiorespiratory capacity (3). During the second week, after complete recovery from the physical test, they underwent dual-energy X-ray absorptiometry (4) and proton magnetic resonance spectroscopy (5) tests, to assess their body and muscle composition, respectively.

• 

  Fig. 2 Box plot showing the distribution of the serum musclin concentration in controls and subjects with metabolic syndrome. Each dot corresponds to a subject. The thicker horizontal lines correspond to the medians, whose values are presented in the text. aP<0.05 using the Mann-Whitney U test.

• 

  Fig. 3 Pearson correlation heatmap to assess the relationship between musclin and biochemical and body composition variables in humans. Ln(musclin) showed positive and significant correlations with biochemical variables such as ln(homeostatic model assessment of insulin resistance [HOMA-IR]) (r=0.34), ln(insulin) (r=0.32) and fasting blood glucose (FBG, mg/dL) (r=0.23). It also showed positive correlations with the parameters of abdominal obesity, waist circumference (WC, cm) (r=0.25), and visceral adipose tissue (VAT, g) (r=0.22). The correlation of musclin and parameters of global adiposity such as body fat percentage (fat %) (r=−0.33) and FM (r=−0.25) was negative. Musclin showed a positive correlation with a measure of lean mass, thigh lean mass corrected for body mass (TLM/BM, kg/kg) (r=0.26), but not to muscle fiber type composition, area of type II fibers (FT II, %) (r=0.05). There was no correlation between musclin and body mass index (BMI, kg/m2). Other significant correlations are also highlighted. The strength of each association is indicated by the intensity of the color grades, according to the key shown on the right. FM h2, fat mass corrected for stature (kg/m2); LM h2, total lean mass corrected for stature (kg/m2). aAll * indicate P<0.05.

• 

  Fig. 4 Heatmap of Pearson correlations to assess the relationship between musclin and variables of physical capacity in humans. There was no correlation between ln(musclin) and any of the variables related to physical endurance and cardiorespiratory fitness obtained during the ergospirometry test (P>0.05 in all cases). The strength of each association is indicated by the intensity of the color grades, according to the key shown on the right. VO2p, VO2peak (mL O2/min); VO2p/BM, VO2peak corrected for body mass (mL O2/kg·min); VO2p/LM, VO2peak corrected for total lean mass (mL O2/kg·min); HRmax, maximum heart rate (bpm); Vmax, maximum velocity (mile/hr); Tmax, maximum time of work (min); VCO2p, VCO2peak (mL CO2/min); VCO2p/BM, VCO2peak corrected for body mass (mL CO2/kg·min); RER, respiratory exchange ratio; RHR1 and 5, recovery heart rate at minute 1 and 5 (bpm). aSome significant correlations highlighted by the *(P>0.05), demonstrate the reliability of the data.

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