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

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.

• Authors: Pouneh K Fazeli, Madhusmita Misra, Mark Goldstein, Karen K Miller, Anne Klibanski
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 95 Issue 1 Pg. 369-74 (Jan 2010) ISSN: 1945-7197 [Electronic] United States
• PMID: 19926712 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Blood Glucose
• Insulin
• Leptin
• fibroblast growth factor 21
• Human Growth Hormone
• Fibroblast Growth Factors
• Insulin-Like Growth Factor I

Topics

• Adolescent
• Anorexia Nervosa (blood, diagnosis, metabolism)
• Area Under Curve
• Blood Glucose (analysis)
• Body Composition (physiology)
• Case-Control Studies
• Drug Resistance (physiology)
• Female
• Fibroblast Growth Factors (blood, physiology)
• Health
• Human Growth Hormone (blood, physiology)
• Humans
• Insulin (blood)
• Insulin-Like Growth Factor I (analysis)
• Leptin (blood)
• Prognosis