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

J Clin Endocrinol Metab. 2020 Apr 1;105(4):1228-1241. doi: 10.1210/clinem/dgz261.

Abstract

Background: With increased rates of obesity and insulin resistance in youth, development of postprandial dyslipidemia, an important cardiovascular disease risk factor, is a concern. Glucagon-like peptides (ie, GLP-1 and GLP-2) and bile acids have been shown to regulate dietary fat absorption and postprandial lipids in animal models and humans. We hypothesize that the physiological response of GLPs and bile acids to dietary fat ingestion is impaired in adolescents with obesity and this associates with marked postprandial dyslipidemia and insulin resistance.

Methods: In this cross-sectional study, normal weight adolescents and adolescents with obesity 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. Postprandial GLPs were reduced and inversely correlated with postprandial dyslipidemia and insulin resistance. Postprandial bile acids were also diminished, particularly lithocholic acid, a potent stimulator of GLP-1 secretion.

Conclusion: Blunted postprandial GLP and bile acid response to dietary fat ingestion strongly associates with marked postprandial dyslipidemia. Further investigation is needed to assess their potential utility as early biomarkers for postprandial dyslipidemia in adolescents with obesity.

Keywords: Glucagon-Like Peptide 1; bile acids; dyslipidemia; insulin resistance; pediatric obesity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Bile Acids and Salts / metabolism*
  • Biomarkers / metabolism
  • Canada / epidemiology
  • Child
  • Cross-Sectional Studies
  • Dyslipidemias / epidemiology*
  • Dyslipidemias / metabolism
  • Dyslipidemias / pathology
  • Female
  • Follow-Up Studies
  • Gastrointestinal Tract / metabolism
  • Gastrointestinal Tract / pathology*
  • Glucagon-Like Peptide 1 / metabolism*
  • Glucagon-Like Peptide 2 / metabolism*
  • Humans
  • Hyperinsulinism / epidemiology*
  • Hyperinsulinism / metabolism
  • Hyperinsulinism / pathology
  • Male
  • Pediatric Obesity / physiopathology*
  • Postprandial Period
  • Prognosis
  • Young Adult

Substances

  • Bile Acids and Salts
  • Biomarkers
  • Glucagon-Like Peptide 2
  • Glucagon-Like Peptide 1

Grant support