Growth differentiation factor 15 (GDF15) is associated with non-alcoholic fatty liver disease (NAFLD) in youth with overweight or obesity

Nutr Diabetes. 2022 Feb 22;12(1):9. doi: 10.1038/s41387-022-00187-2.

Abstract

Objective: Growth differentiation factor 15 (GDF15) has been associated with food intake and weight regulation in response to metabolic stress. In animal models, it has been noted that it may play a role in the progression of non-alcoholic fatty liver disease (NAFLD), the leading cause of chronic liver disease in children.

Design: In the current study, we explored the association of circulating plasma concentrations of GDF15 with NAFLD in youth with overweight/obesity, and whether changes in plasma concentrations in GDF15 parallel the changes in intrahepatic fat content (HFF%) over time.

Methods: Plasma GDF15 concentrations were measured by ELISA in 175 youth with overweight/obesity who underwent an oral glucose tolerance test (OGTT) and magnetic resonance imaging (MRI) to assess intrahepatic, visceral, and subcutaneous fat. Baseline fasting GDF15 concentrations were measured in twenty-two overweight/obese youth who progressed (n = 11) or regressed (n = 11) in HFF% by more than 30% of original over a 2-year period.

Results: Youth with NAFLD had significantly higher plasma concentrations of GDF15 than those without NAFLD, independent of age, sex, ethnicity, BMI z-score (BMIz), and visceral fat (P = 0.002). During the OGTT, there was a decline in plasma GDF15 concentrations from 0 to 60 min, but GDF15 concentrations returned to basal levels by the end of the study. There was a statistically significant association between change in HFF% and change in GDF15 (P = 0.008; r2 = 0.288) over ~2 years of follow-up.

Conclusions: These data suggest that plasma GDF15 concentrations change with change in intrahepatic fat content in youth with overweight/obesity and may serve as a biomarker for NAFLD in children.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Growth Differentiation Factor 15* / metabolism
  • Humans
  • Intra-Abdominal Fat / metabolism
  • Liver / metabolism
  • Non-alcoholic Fatty Liver Disease* / complications
  • Non-alcoholic Fatty Liver Disease* / metabolism
  • Obesity* / complications
  • Overweight* / complications

Substances

  • GDF15 protein, human
  • Growth Differentiation Factor 15