Fibroblast growth factor-21 may mediate growth hormone resistance in anorexia nervosa.
BACKGROUND
Anorexia nervosa (AN), a state of chronic nutritional deprivation, is characterized by GH resistance with elevated GH levels and decreased levels of IGF-I. Fibroblast growth factor (FGF)-21, a hormone produced in the liver and adipocytes, is induced in the liver by fasting and peroxisome proliferator-activated receptor-alpha agonists. In a transgenic mouse model, FGF-21 reduces IGF-I levels by inhibiting signal transducer and activator of transcription-5, a mediator of the intracellular effects of GH.


OBJECTIVE
The objective of the study was to investigate the relationship between FGF-21, GH, and IGF-I in AN.


METHODS
This was a cross-sectional study.


METHODS
The study was conducted at a clinical research center.


METHODS
Patients included 23 girls: 11 with AN (16.5 +/- 0.6 yr) and 12 normal-weight controls (15.7 +/- 0.5 yr).


METHODS
There were no interventions.


METHODS
We measured fasting FGF-21, glucose, insulin, IGF-I, and total area under the curve for GH (GH-AUC) and leptin during 12-h overnight frequent sampling.


RESULTS
FGF-21 levels were significantly higher in AN compared with controls, and there was a positive correlation between FGF-21 and GH-AUC (P = 0.03) after controlling for percent body fat and insulin resistance. In subjects with elevated FGF-21 levels, there was a strong inverse association between FGF-21 and IGF-I (R = -0.88, P = 0.004). FGF-21 strongly correlated with total area under the curve for leptin (R = 0.67, P = 0.02).


CONCLUSIONS
FGF-21 levels are higher in AN independent of the effects of percent body fat and insulin resistance. The positive association between FGF-21 and GH-AUC and the inverse association between elevated FGF-21 levels and IGF-I suggests that above the normal range, FGF-21 may mediate a state of GH resistance in AN.
Fazeli
Pouneh K
PK
Neuroendocrine Unit,Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
Misra
Madhusmita
M
Goldstein
Mark
M
Miller
Karen K
KK
Klibanski
Anne
A
D000293:Adolescent; D000856:Anorexia Nervosa / Q000097:blood* / Q000175:diagnosis / Q000378:metabolism; D019540:Area Under Curve; D001786:Blood Glucose / Q000032:analysis; D001823:Body Composition / Q000502:physiology; D016022:Case-Control Studies; D004351:Drug Resistance / Q000502:physiology; D005260:Female; D005346:Fibroblast Growth Factors / Q000097:blood / Q000502:physiology*; D006262:Health; D019382:Human Growth Hormone / Q000097:blood / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D020738:Leptin / Q000097:blood; D011379:Prognosis
D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; C414620:fibroblast growth factor 21; D019382:Human Growth Hormone; D005346:Fibroblast Growth Factors; D007334:Insulin-Like Growth Factor I