Background: Growth hormone (GH) plays an important role in modifying body composition. In acromegaly, a state of chronic GH/IGF-I excess, visceral and ectopic fat mass, especially in the liver, are significantly reduced. The aim of this study was to investigate the impact of GH/IGF-I on hepatocellular lipid content (HCL) and energy metabolism in a non-acromegalic cohort of patients with and without non-alcoholic fatty liver disease (NAFLD).
Methods: We performed a cross-sectional study in 76 non-acromegalic individuals (36 females). Concentrations of glucose, insulin, c-peptide and GH were measured every 30 minutes during a standardized 2-h-75g oral glucose tolerance test (OGTT). Insulin sensitivity was estimated by the oral glucose insulin sensitivity index (OGIS). IGF-I was measured prior to the OGTT and was given as the percentage of the sex-, age-, and assay specific upper limit of normal (IGF-I ULN). Liver parameters, like HCL and ATP synthesis rate (kATP), as well as high energy phosphorous metabolites were analysed using 1H- as well as 31P- magnetic resonance spectroscopy (MRS) at 7 Tesla. NAFLD was defined as HCL >5.5%.
Results: In the whole cohort (age: 43.4+-15.3y; BMI: 25.7+-4.3 kg/m2; IGFI-ULN: 65.7+-17.2% [IQR 33.6-102.6%]) the median HCL was 2.79% [IQR 1.35-9.5%] with 27 patients presenting with a HCL higher than 5.5% indicating NAFLD. Fasting GH (0.21 [0.1; 0.6] ng/ml vs 0.67 [0.2; 2.5] ng/ml;P=0.0055), as well as dynamic GH levels during OGTT (AUCGH: 15.30 [7.2; 25.6] ng/ml/min vs 48.8 [25.7; 143.2] ng/ml/min;P=0.0002). IGF1-ULN correlated significantly with high-energy phosphorous metabolites but did not correlate with kATP in the whole cohort. In the multiple logistic regression analysis IGF1-ULN as well as fasting glucose were next to BMI and OGIS a significant, independent predictor for NAFLD.
Conclsion: In summary, here we show that increased HCL is associated with lower fasting and post-glucose-load GH concentrations in otherwise healthy individuals with or without NAFLD, while both GH and IGF-I independently relate to the presence of NAFLD. The relationship between GH/IGF-I metabolism and HCL could be further investigated as a potential therapeutical target in patients with NAFLD.
21 May 2022 - 24 May 2022