The GH/IGF-1 Axis Is Associated With Intrahepatic Lipid Content and Hepatocellular Damage in Overweight/Obesity

Obesity is a state of relative growth hormone (GH) deficiency, and GH has been identified as a candidate disease-modifying target in nonalcoholic fatty liver disease (NAFLD) because of its lipolytic and anti-inflammatory properties. However, the GH/IGF-1 axis has not been well characterized in NAFLD.

We aimed to investigate serum GH and IGF-1 levels in relation to intrahepatic lipid content (IHL) and markers of hepatocellular damage and fibrosis in NAFLD.

This cross-sectional study included 102 adults (43% women; age 19-67; BMI ≥ 25 kg/m2) without type 2 diabetes. IHL was measured by magnetic resonance spectroscopy; NAFLD was defined by ≥ 5% IHL. Peak-stimulated GH in response to GH releasing hormone and arginine was assessed as was serum IGF-1 (LC/MS).

There was no difference in mean age, BMI, or sex distribution in NAFLD vs controls. Mean (± SD) IHL was higher in NAFLD vs controls (21.8 ± 13.3% vs 2.9 ± 1.1%, P < 0.0001). Mean peak-stimulated GH was lower in NAFLD vs controls (9.0 ± 6.3 vs 15.4 ± 11.2 ng/mL, P = 0.003), including after controlling for age, sex, visceral adipose tissue, and fasting glucose. In a stepwise model, peak-stimulated GH predicted 14.6% of the variability in IHL (P = 0.004). Higher peak-stimulated GH was also associated with lower ALT. Higher serum IGF-1 levels were associated with lower risk of liver fibrosis by Fibrosis-4 scores.

Individuals with NAFLD have lower peak-stimulated GH levels but similar IGF-1 levels as compared to controls. Higher peak-stimulated GH levels are associated with lower IHL and less hepatocellular damage. Higher IGF-1 levels are associated with more favorable fibrosis risk scores. These data implicate GH and IGF-1 as potential disease modifiers in the development and progression of NAFLD.