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Abnormal body composition, leptin & ghrelin levels in children with mitochondrial trifunctional protein (TFP) deficiency
Author(s) -
Gillingham Melanie B.,
Purnell Jonathan Q.,
Harding Cary O.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a589-a
Subject(s) - endocrinology , medicine , ghrelin , leptin , insulin , lean body mass , hormone , obesity , body weight
Objective Changes in mitochondrial fatty acid oxidation in the hypothalamus and in peripheral tissues are thought to be involved in the regulation of food intake, energy expenditure, and body weight. We hypothesized that children with inherited disorders of long‐chain fatty acid oxidation such as mitochondrial trifunctional protein (TFP) deficiency would exhibit altered body composition and abnormal levels of hormones involved in body weight regulation. Methods To test this hypothesis, body composition (DEXA) and fasting, and post‐prandial plasma glucose (glucose oxidase), insulin, leptin and total ghrelin levels (radioimmunoassay) were measured in nine subjects with TFP deficiency and compared to published control data. Insulin sensitivity was estimated using the QUICKI model. Results 3 were obese, 2 were under weight and 4 were normal weight as determined by BMI percentile. All subjects exhibited a lower lean body mass and higher fat mass than expected regardless of BMI. Plasma leptin levels were significantly higher than in age, gender, BMI, and Tanner stage‐matched published controls. Fasting plasma glucose, insulin and QUICKI indices were within normal ranges, despite their increased adiposity. While plasma ghrelin levels negatively correlated with BMI percentile as reported in adults, plasma ghrelin suppression appeared to be enhanced in obese subjects (33%) vs. lean subjects (10%). Conclusions These data suggest that children with TFP deficiency have abnormal body composition and dysregulation of peripheral hormonal signals involved in weight regulation. Supported by PHS Grant 5 M01 RR000334, F32 DK065400, and OHSU Center for the Study of Weight Regulation.