TY - JOUR

T1 - Circulating but not faecal short-chain fatty acids are related to insulin sensitivity, lipolysis and GLP-1 concentrations in humans

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.

PY - 2019/8/29

Y1 - 2019/8/29

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.

AB - 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.

KW - Adult

KW - Aged

KW - Cross-Sectional Studies

KW - Fatty Acids, Volatile/analysis

KW - Feces/chemistry

KW - Female

KW - Gastrointestinal Microbiome

KW - Glucagon-Like Peptide 1/blood

KW - Humans

KW - Insulin Resistance

KW - Insulin/blood

KW - Lipolysis

KW - Male

KW - Middle Aged

KW - Young Adult

UR - http://www.scopus.com/inward/record.url?scp=85071622595&partnerID=8YFLogxK

U2 - 10.1038/s41598-019-48775-0

DO - 10.1038/s41598-019-48775-0

M3 - Article

C2 - 31467327

VL - 9

JO - Scientific reports

JF - Scientific reports

SN - 2045-2322

IS - 1

M1 - 12515

ER -