Duodenal L cell density correlates with features of metabolic syndrome and plasma metabolites

TY - JOUR

T1 - Duodenal L cell density correlates with features of metabolic syndrome and plasma metabolites

AU - Van Baar, Annieke C.G.

AU - Prodan, Andrei

AU - Wahlgren, Camilla D.

AU - Poulsen, Steen S.

AU - Knop, Filip K.

AU - Groen, Albert K.

AU - Bergman, Jacques J.

AU - Nieuwdorp, Max

AU - Levin, Evgeni

PY - 2018

Y1 - 2018

N2 - Background: Enteroendocrine cells are essential for the regulation of glucose metabolism, but it is unknown whether they are associated with clinical features of metabolic syndrome (MetS) and fasting plasma metabolites. Objective: We aimed to identify fasting plasma metabolites that associate with duodenal L cell, K cell and delta cell densities in subjects with MetS with ranging levels of insulin resistance. Research design and methods: In this cross-sectional study, we evaluated L, K and delta cell density in duodenal biopsies from treatment-naïve males with MetS using machinelearning methodology. Results: We identified specific clinical biomarkers and plasma metabolites associated with L cell and delta cell density. L cell density was associated with increased plasma metabolite levels including symmetrical dimethylarginine, 3-aminoisobutyric acid, kynurenine and glycine. In turn, these L cell-linked fasting plasma metabolites correlated with clinical features of MetS. Conclusions: Our results indicate a link between duodenal L cells, plasma metabolites and clinical characteristics of MetS. We conclude that duodenal L cells associate with plasma metabolites that have been implicated in human glucose metabolism homeostasis. Disentangling the causal relation between L cells and these metabolites might help to improve the (small intestinal-driven) pathophysiology behind insulin resistance in human obesity.

AB - Background: Enteroendocrine cells are essential for the regulation of glucose metabolism, but it is unknown whether they are associated with clinical features of metabolic syndrome (MetS) and fasting plasma metabolites. Objective: We aimed to identify fasting plasma metabolites that associate with duodenal L cell, K cell and delta cell densities in subjects with MetS with ranging levels of insulin resistance. Research design and methods: In this cross-sectional study, we evaluated L, K and delta cell density in duodenal biopsies from treatment-naïve males with MetS using machinelearning methodology. Results: We identified specific clinical biomarkers and plasma metabolites associated with L cell and delta cell density. L cell density was associated with increased plasma metabolite levels including symmetrical dimethylarginine, 3-aminoisobutyric acid, kynurenine and glycine. In turn, these L cell-linked fasting plasma metabolites correlated with clinical features of MetS. Conclusions: Our results indicate a link between duodenal L cells, plasma metabolites and clinical characteristics of MetS. We conclude that duodenal L cells associate with plasma metabolites that have been implicated in human glucose metabolism homeostasis. Disentangling the causal relation between L cells and these metabolites might help to improve the (small intestinal-driven) pathophysiology behind insulin resistance in human obesity.

KW - Enteroendocrine cells

KW - Incretins

KW - Machine-learning methodology

KW - Metabolic syndrome

KW - Plasma metabolites

U2 - 10.1530/EC-18-0094

DO - 10.1530/EC-18-0094

M3 - Journal article

C2 - 29669802

AN - SCOPUS:85046899950

SN - 2049-3614

VL - 7

SP - 673

EP - 680

JO - Endocrine Connections

JF - Endocrine Connections

IS - 5

ER -