Postprandial Dyslipidemia, Hyperinsulinemia, and Impaired Gut Peptides/Bile Acids in Adolescents with Obesity - Supplemental Files

Abstract

Background: Postprandial dyslipidemia strongly associates with obesity and insulin resistance and is an important cardiovascular disease risk factor. Glucagon-like peptides (i.e. GLP-1 and GLP-2) and bile acids have been shown to regulate dietary fat absorption and postprandial lipids in animal models and some human studies. Using healthy adolescents and adolescents with obesity as an experimental model, we aimed to determine the link between postprandial response of GLPs and bile acids to dietary fat and development of postprandial dyslipidemia. Methods: Normal weight (NW) adolescents and those with obesity and mild (OB-MIR) or overt insulin resistance (OB-IR) underwent a 6-hour oral fat tolerance test. The postprandial lipoprotein phenotype profile was determined using various assays, including nuclear magnetic resonance spectroscopy, to characterize lipoprotein particle number, size, lipid content, and apolipoproteins. GLP-1 and GLP-2 were quantified by electrochemiluminescent immunoassays. Total bile acids were measured by an automated enzymatic cycling colorimetric method and the bile acid profile by mass spectrometry. Results: Adolescents with obesity exhibited fasting and postprandial dyslipidemia, particularly augmented postprandial excursion of large triglyceride-rich lipoproteins that worsened with increasing insulin resistance severity. Postprandial GLPs were reduced and inversely correlated with postprandial dyslipidemia. Postprandial bile acids were also diminished, particularly lithocholic acid, a potent stimulator of GLP-1 secretion. Conclusion: Blunted postprandial GLPs and bile acids may contribute to the pathogenesis of disordered lipid and lipoprotein homeostasis. Further investigation is needed to assess their potential utility as early biomarkers for postprandial dyslipidemia in adolescents with obesity and insulin resistance.