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

Research output: Contribution to journalArticleResearchpeer review

Authors

  • M. Müller
  • M.A. González Hernández
  • G.H. Goossens
  • D. Reijnders
  • J.J. Holst
  • J.W.E. Jocken
  • H. van Eijk
  • E.E. Canfora
  • E.E. Blaak

External Research Organisations

  • Maastricht University Medical Center
  • University of Copenhagen
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Details

Original languageEnglish
Article number12515
JournalScientific reports
Volume9
Issue number1
Early online date29 Aug 2019
Publication statusE-pub ahead of print - 29 Aug 2019
Externally publishedYes

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/m 2, 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.

Keywords

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

ASJC Scopus subject areas

Sustainable Development Goals

Cite this

Circulating but not faecal short-chain fatty acids are related to insulin sensitivity, lipolysis and GLP-1 concentrations in humans. / Müller, M.; González Hernández, M.A.; Goossens, G.H. et al.
In: Scientific reports, Vol. 9, No. 1, 12515, 29.08.2019.

Research output: Contribution to journalArticleResearchpeer review

Müller, M, González Hernández, MA, Goossens, GH, Reijnders, D, Holst, JJ, Jocken, JWE, van Eijk, H, Canfora, EE & Blaak, EE 2019, 'Circulating but not faecal short-chain fatty acids are related to insulin sensitivity, lipolysis and GLP-1 concentrations in humans', Scientific reports, vol. 9, no. 1, 12515. https://doi.org/10.1038/s41598-019-48775-0
Müller, M., González Hernández, M. A., Goossens, G. H., Reijnders, D., Holst, J. J., Jocken, J. W. E., van Eijk, H., Canfora, E. E., & Blaak, E. E. (2019). Circulating but not faecal short-chain fatty acids are related to insulin sensitivity, lipolysis and GLP-1 concentrations in humans. Scientific reports, 9(1), Article 12515. Advance online publication. https://doi.org/10.1038/s41598-019-48775-0
Müller M, González Hernández MA, Goossens GH, Reijnders D, Holst JJ, Jocken JWE et al. Circulating but not faecal short-chain fatty acids are related to insulin sensitivity, lipolysis and GLP-1 concentrations in humans. Scientific reports. 2019 Aug 29;9(1):12515. Epub 2019 Aug 29. doi: 10.1038/s41598-019-48775-0
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title = "Circulating but not faecal short-chain fatty acids are related to insulin sensitivity, lipolysis and GLP-1 concentrations in humans",
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/m 2, 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. ",
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AU - Müller, M.

AU - González Hernández, M.A.

AU - Goossens, G.H.

AU - Reijnders, D.

AU - Holst, J.J.

AU - Jocken, J.W.E.

AU - van Eijk, H.

AU - Canfora, E.E.

AU - Blaak, E.E.

N1 - We would kindly like to thank all study participants, Wendy Sluijsman, Yvonne Essers, Nicole Hoebers, Hasibe Aydeniz and Jos Stegen for their excellent technical support. The studies summarized in this manuscript were fundend by TI Food and Nutrition, a public–private partnership on precompetitive research in food and nutrition research.

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N2 - 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/m 2, 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.

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