Literature DB >> 19926712

Fibroblast growth factor-21 may mediate growth hormone resistance in anorexia nervosa.

Pouneh K Fazeli1, Madhusmita Misra, Mark Goldstein, Karen K Miller, Anne Klibanski.   

Abstract

CONTEXT: 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.
DESIGN: This was a cross-sectional study.
SETTING: The study was conducted at a clinical research center. PATIENTS: Patients included 23 girls: 11 with AN (16.5 +/- 0.6 yr) and 12 normal-weight controls (15.7 +/- 0.5 yr).
INTERVENTIONS: There were no interventions. MAIN OUTCOME MEASURES: 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.

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Year:  2009        PMID: 19926712      PMCID: PMC2805486          DOI: 10.1210/jc.2009-1730

Source DB:  PubMed          Journal:  J Clin Endocrinol Metab        ISSN: 0021-972X            Impact factor:   5.958


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