Muscle, bone signaling imbalances found in non-obese PWS children
Such imbalances may 'contribute to future metabolic disorders,' per study
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Non-obese children with Prader-Willi syndrome (PWS) have imbalances in the blood levels of signaling molecules that facilitate communication between muscles, bones, and fat tissue, a single-center study from Poland suggests.
According to the researchers, such imbalances “may impair muscle development and bone metabolism” in “normal-weight children” with the rare genetic disorder.
Further, “these imbalances could … contribute to future metabolic disorders in patients with PWS,” the team wrote.
Despite undergoing standard growth hormone (GH), or somatropin, therapy and dietary intervention, the PWS children in this small study also showed changes in body composition compared with healthy children, the researchers noted.
The study, “Myokine Levels in Relation to Bone Markers and Adipokines in Children with Prader-Willi Syndrome During Growth Hormone Therapy and Dietary Intervention,” was published in the International Journal of Molecular Sciences.
PWS is marked by a wide range of signs and symptoms that include short stature, increased hunger, obesity, low muscle tone, and muscle weakness. Low GH levels are common in these kids.
Body composition is typically altered in PWS kids
Individuals with PWS also have weaker bones and lower bone density, increasing the risk of fractures and other bone-related problems. In addition, their body composition is typically altered, with more body fat, less muscle mass, and reduced muscle function.
In the body, muscles, bones, and fat tissue communicate with each other by releasing signaling molecules. Muscles release myokines, bones release osteokines, and fat tissue releases adipokines, all of which help to regulate muscle growth, bone strength, energy use, and metabolism.
While the so-called crosstalk between muscle, bone, and fat may be disrupted in people with PWS, data on this interplay “in normal-weight children with [PWS] undergoing growth hormone (GH) therapy and dietary interventions are limited,” the researchers wrote.
To learn more, a research team investigated how myokines are linked to bone health, adipokines, and body composition in children with PWS.
After collecting blood samples from 26 children with PWS — 15 girls and 11 boys with a mean age of 6.6 years — and an equal number of sex- and age-matched healthy children, the team measured myokine, osteokine, and adipokine levels.
All of the children were recruited at a single center in Warsaw. The youngsters with PWS were undergoing standard GH therapy and were on a low-energy diet with a balance of carbohydrates, proteins, and fats.
Data showed that the PWS children had a significantly lower daily energy intake than the healthy children. Total and animal protein intake were similar to those of controls, but PWS patients ate significantly less plant protein, fat, and carbs.
There were no significant group differences in terms of height and weight, but body mass index — a ratio of height and weight commonly used as a proxy of body fat — was 7% lower in the PWS group.
Lower-than-expected bone density found for children in study
While those results could suggest less body fat, the children with PWS showed a trend toward more mean fat mass and significantly lower lean mass (total body weight minus all fat mass). The PWS children also had a significantly higher fat-to-lean mass ratio relative to the healthy youth.
The researchers also found significantly more pronounced lower-than-expected bone density (excluding the skull) for their age, sex, and body size among the children with PWS.
Regarding myokines, PWS children showed significantly higher blood levels of insulin-like growth factor-1 (IGF-I), which helps build bone and supports tissue repair and regeneration, compared with healthy controls. The PWS group also had significantly lower levels of IGF-binding protein-2, which regulates IGF-I, and irisin, released by muscles during activity.
Levels of certain osteokines were also significantly altered in the PWS children. Among those affected were osteocalcin, which helps regulate bone strength, muscle function, and energy metabolism, and periostin, a protein involved in bone repair and strength.
In terms of adipokines, the PWS group also showed a significantly higher free-leptin index, reflecting greater resistance to leptin, a hormone that controls hunger and energy, and significantly higher levels of high-molecular-weight adiponectin. That is the most active form of a protein that regulates blood sugar levels, fat-based energy production, and insulin sensitivity. Insulin sensitivity refers to how effectively body cells respond to the hormone insulin to take up blood sugar.
Also, proinsulin, a precursor of insulin, was significantly elevated in PWS children, suggesting problems with insulin production or early insulin resistance.
The scientists then conducted correlation analyses across myokines, osteokines, and adipokines in children with PWS.
Among the notable results, lower levels of the myokine irisin were significantly associated with lower activity of bone alkaline phosphatase, a bone formation marker. Higher myostatin, which limits muscle growth, was significantly linked to lower lean mass.
“It seems that the lower levels of irisin and negative association of [myostatin] with lean mass affect muscle growth processes and consequently be one of the reasons for the lower lean mass observed in the studied children with PWS,” the team wrote.
