High-coverage targeted lipidomics revealed novel profile of serum lipid dysregulation in adult growth hormone deficiency.

Purpose: Patients with adult growth hormone deficiency (AGHD) are at increased risk of metabolic syndrome. Despite extensive research efforts in recent decades, the lipid metabolism pattern of AGHD has yet to be thoroughly characterized.

Methods: In this study, we used lipidomics analysis of fasting serum samples from 30 AGHD patients due to intracranial germ cell tumors (iGCTs) and 30 age-, gender-, and body mass index (BMI)-matched healthy controls to investigate the serum lipidomic pattern of AGHD patients due to iGCTs. We meticulously quantified 534 serum lipids from 29 classes using high-coverage targeted lipidomics technology in conjunction with a robust bioinformatics pipeline.

Results: Our results revealed an AGHD-specific dynamic change in serum lipidomic profile, manifested by higher overall levels of many lipid subclasses, including triacylglycerols (TAGs), diacylglycerols (DAGs), phosphatidylglycerols, phosphatidylethanolamines (PE), phosphatidylcholines (PC), phosphatidylinositols, ceramides, and bis(monoacylglycerol)phosphates than in healthy controls, and a distinct lowering level in alkyl PE (PE-O) and alkyl PC (PC-O). AGHD individuals with non-alcoholic fatty liver disease showed specific changes in higher TAG and DAG subclass levels. Alterations in lipid profiles may contribute to metabolic dysregulation in AGHD patients. TAGs, PCs, and PE-fatty acids positively correlated with BMI, fasting insulin, insulin resistance index, and adverse lipid parameters. In contrast, ether-linked PE-O, PC-O, and LysoPE-O showed a negative correlation.

Conclusions: This study has significantly expanded the current understanding of lipid dysregulation in AGHD patients due to iGCT. These findings can potentially guide future research and the development of monitoring and intervention strategies.