Circulating but not faecal short-chain fatty acids are related to insulin sensitivity, lipolysis and GLP-1 concentrations in humans

Sci Rep. 2019 Aug 29;9(1):12515. doi: 10.1038/s41598-019-48775-0.

Abstract

Microbial-derived short-chain fatty acids (SCFA) acetate, propionate and butyrate may provide a link between gut microbiota and whole-body insulin sensitivity (IS). In this cross-sectional study (160 participants, 64% male, BMI: 19.2-41.0 kg/m2, normal or impaired glucose metabolism), associations between SCFA (faecal and fasting circulating) and circulating metabolites, substrate oxidation and IS were investigated. In a subgroup (n = 93), IS was determined using a hyperinsulinemic-euglycemic clamp. Data were analyzed using multiple linear regression analysis adjusted for sex, age and BMI. Fasting circulating acetate, propionate and butyrate concentrations were positively associated with fasting GLP-1 concentrations. Additionally, circulating SCFA were negatively related to whole-body lipolysis (glycerol), triacylglycerols and free fatty acids levels (standardized (std) β adjusted (adj) -0.190, P = 0.023; std β adj -0.202, P = 0.010; std β adj -0.306, P = 0.001, respectively). Circulating acetate and propionate were, respectively, negatively and positively correlated with IS (M-value: std β adj -0.294, P < 0.001; std β adj 0.161, P = 0.033, respectively). We show that circulating rather than faecal SCFA were associated with GLP-1 concentrations, whole-body lipolysis and peripheral IS in humans. Therefore, circulating SCFA are more directly linked to metabolic health, which indicates the need to measure circulating SCFA in human prebiotic/probiotic intervention studies as a biomarker/mediator of effects on host metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cross-Sectional Studies
  • Fatty Acids, Volatile / analysis*
  • Fatty Acids, Volatile / blood
  • Feces / chemistry*
  • Female
  • Gastrointestinal Microbiome
  • Glucagon-Like Peptide 1 / blood*
  • Humans
  • Insulin / blood
  • Insulin Resistance*
  • Lipolysis
  • Male
  • Middle Aged
  • Young Adult

Substances

  • Fatty Acids, Volatile
  • Insulin
  • Glucagon-Like Peptide 1