Prader Willi Syndrome Clinical Trial
Official title:
Post Exercise Irisin Levels in PWS Patients
Post exercise irisin levels in PWS patients Obesity, short stature, hypogonadism, hypotonia
and impaired cognition are the major clinical features of Prader-Willi syndrome (PWS), a
complex neurogenetic disorder due to lack of expression of paternal genes in the chromosomal
region 15q11-13. Abnormal body composition with decreased muscle mass and increased fat mass
contributes to low resting energy expenditure in PWS. Severe caloric restriction in the
range of 800 kcal per day along with daily exercise regimens are needed to prevent weight
gain and complications of obesity in this population.
Brown adipose tissue (BAT) once thought to be present only in infants, but now known to be
present in adults as well, differs from the more abundant white adipose tissue (WAT) by
dissipating energy through thermogenesis as a result of increased activity of the
mitochondrial uncoupling protein (UCP-1). Recently evidence shows that exercise activates
mitochondrial UCP-1 in subcutaneous WAT cells resulting in conversion of WAT to BAT-like
adipocytes (Beige or BRITE adipose tissue). Various factors including natriuretic peptides,
interleukin-6 and myokines (irisin, fibroblast growth factor 21, and ß-aminoisobutyric acid)
appear to mediate the effects of exercising muscle on subcutaneous adipocytes.
Decreased amount and/or activity of BAT might contribute to the lower energy expenditure and
extreme difficulty in weight-control in PWS. Lower levels or decreased myokine production
could result in failure to convert subcutaneous WAT to Beige or BAT-like adipocytes, and
therefore minimize or negate the otherwise beneficial metabolic effects of exercise. Direct
measurement of peak oxygen uptake in PWS adults show that this population has markedly lower
VO2 values compared with normal BMI-matched controls. BAT activity in vivo can be accurately
measured only by performing PET/CT scans which include administrating radioactive tracers.
For ethical reasons, direct assessment of BAT is not possible for purposes of clinical
research in PWS individuals.
The investigators propose to study humoral responses to exercise in 16 (8 males) PWS
adolescents and young adults and compare results with responses in a similar number of sex,
age, and BMI-matched controls. At an initial one-hour meeting study participants will learn
to perform aerobic (treadmill) exercise and resistance training under the supervision of an
experienced exercise physiologist. Exercise intensity will be assessed by direct measurement
of VO2 max. On a different day, a blood sample will be drawn before and immediately at the
conclusion of the same exercise regimen. Blood samples will be assayed for irisin,
interleukin-6, atrial natriuretic peptide, FGF-21, in addition to glucose, growth hormone,
cortisol, norepinephrine, and lactate.
The investigators hypothesize that PWS participants will show weaker humoral responses to
similar exercise regimens compared to normal control subjects. Data showing lower levels of
myokines, such as irisin, following exercise in PWS might suggest that inadequate conversion
of WAT to BAT-like adipocytes in subcutaneous adipose tissue results in decreased
thermogenesis and abnormally low energy expenditure in this population. Potentially,
development of pharmacologic agents which mimic irisin or other myokines by activating UCP-1
and converting WAT to BAT-like adipocytes could offer a new approach to weight-control in
PWS individuals.
n/a
Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic
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