Resting metabolic rate, plasma leptin concentrations, leptin receptor expression, and adipose tissue measured by whole-body magnetic resonance imaging in women with Prader-Willi syndrome.
BACKGROUND
Obesity in Prader-Willi syndrome (PWS) may be related to abnormalities in the adipocyte-leptin-hypothalamic pathway and may be exacerbated by reductions in the resting metabolic rate (RMR).


OBJECTIVE
We compared body composition, body-composition- adjusted RMR, and adiposity-adjusted plasma leptin between women with PWS and control women. We also examined leptin receptor expression in the PWS group.


METHODS
We studied body composition using whole-body magnetic resonance imaging and measured plasma leptin by radioimmunoassay in 45 control women aged 18-56 y and in 13 women with PWS aged 20-38 y. RMR was measured by indirect calorimetry in 41 control women and in 8 women with PWS. Age, body composition, and regional adipose tissue (AT) depots were corrected for by multiple regression analysis. Messenger RNA expression of the leptin receptor was examined by reverse transcriptase-polymerase chain reaction in lymphocytes.


RESULTS
In the PWS group, fat mass was greater after correction for fat-free mass, and RMR was normal after correction for both fat-free mass and fat mass. Leptin was influenced primarily by subcutaneous AT volume in both subject groups. Leptin concentrations were not significantly different between the 2 groups after adjustment for age and AT content or distribution. Full-length leptin receptor messenger RNA was expressed in the lymphocytes of the PWS group.


CONCLUSIONS
Differences in RMR in women with PWS are explained by abnormal body composition, suggesting that energy expenditure is normal at the tissue level in PWS. There is no evidence that defective leptin production causes obesity in PWS, and leptin receptor deficiency is not a primary consequence of the gene defects leading to leptin resistance.
Goldstone
Anthony P
AP
Endocrine Unit, the Department of Dietetics, MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, London, United Kingdom.
Brynes
Audrey E
AE
Thomas
E Louise
EL
Bell
Jimmy D
JD
Frost
Gary
G
Holland
Anthony
A
Ghatei
Mohammad A
MA
Bloom
Stephen R
SR
D000273:Adipose Tissue / Q000033:anatomy & histology* / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D001481:Basal Metabolism / Q000502:physiology*; D001823:Body Composition; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D004734:Energy Metabolism / Q000502:physiology; D005260:Female; D015870:Gene Expression; D006801:Humans; D020738:Leptin / Q000097:blood*; D008214:Lymphocytes / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods; D008875:Middle Aged; D009765:Obesity / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism; D011218:Prader-Willi Syndrome / Q000378:metabolism / Q000503:physiopathology*; D011863:Radioimmunoassay; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D020133:Reverse Transcriptase Polymerase Chain Reaction
D002352:Carrier Proteins; C515448:LEPR protein, human; D020738:Leptin; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin