Fibroblast growth factor 21 (FGF-21) and its relation to obesity, metabolic syndrome, and nonalcoholic fatty liver in children: a longitudinal analysis

J Clin Endocrinol Metab. 2012 Jun;97(6):2143-50. doi: 10.1210/jc.2012-1221. Epub 2012 Mar 21.


Context: Fibroblast growth factor 21 (FGF-21), a potent activator of glucose uptake, has been proposed to be related to insulin resistance, metabolic syndrome (MetS), nonalcoholic fatty liver disease (NAFLD), and weight status.

Objective: Our objective was to study the relationships between FGF-21, parameters of MetS, and NAFLD before and after weight loss in obese children.

Design and setting: This was a cross-sectional comparison between obese and normal-weight children and longitudinal 1-yr follow-up study in obese children participating in a lifestyle intervention in a primary care setting.

Patients: Patients included 60 obese and 40 lean children of same age, gender, and pubertal stage.

Intervention: The outpatient 1-yr intervention program was based on exercise, behavior, and nutrition therapy.

Main outcomes measures: We evaluated fasting serum FGF-21, weight status [body mass index (BMI) expressed as sd score (SDS)], body fat, insulin resistance index (homeostasis model assessment), leptin, transaminases, free fatty acids (FFA), waist circumference, blood pressure, and lipids.

Results: Compared with the normal-weight children, obese children demonstrated significantly (P < 0.001) increased FGF-21, leptin, and homeostasis model assessment levels. FGF-21 was significantly (P < 0.05) correlated to BMI, SDS-BMI, FFA, and leptin both in cross-sectional and longitudinal analyses but not to any additional analyzed parameter. Children with and without MetS or NAFLD did not differ significantly with respect to their FGF-21 concentrations. A decrease of SDS-BMI was associated with a significant (P = 0.038) decrease of FGF-21 levels (mean -34%).

Conclusions: FGF-21 concentrations are reversibly increased in obese children and are related to leptin and FFA. However, our data do not support a significant relationship between FGF-21, insulin resistance, and features of MetS or NAFLD in children.

Trial registration: NCT00435734.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Cross-Sectional Studies
  • Exercise / physiology
  • Fatty Liver / metabolism*
  • Fatty Liver / therapy
  • Female
  • Fibroblast Growth Factors / metabolism*
  • Follow-Up Studies
  • Humans
  • Longitudinal Studies
  • Male
  • Metabolic Syndrome / metabolism*
  • Metabolic Syndrome / therapy
  • Non-alcoholic Fatty Liver Disease
  • Obesity / metabolism*
  • Obesity / therapy*
  • Primary Health Care / methods
  • Risk Reduction Behavior
  • Weight Loss / physiology
  • Weight Reduction Programs*


  • fibroblast growth factor 21
  • Fibroblast Growth Factors

Associated data