The Intestinal Fatty Acid-Enteroendocrine Interplay, Emerging Roles for Olfactory Signaling and Serotonin Conjugates

Abstract

Intestinal enteroendocrine cells (EECs) respond to fatty acids from dietary and microbial origin by releasing neurotransmitters and hormones with various paracrine and endocrine functions. Much has become known about the underlying signaling mechanisms, including the involvement of G-protein coupled receptors (GPCRs), like free fatty acids receptors (FFARs). This review focusses on two more recently emerging research lines: the roles of odorant receptors (ORs), and those of fatty acid conjugates in gut. Odorant receptors belong to a large family of GPCRs with functional roles that only lately have shown to reach beyond the nasal-oral cavity. In the intestinal tract, ORs are expressed on serotonin (5-HT) and glucagon-like-peptide-1 (GLP-1) producing enterochromaffin and enteroendocrine L cells, respectively. There, they appear to function as chemosensors of microbiologically produced short-, and branched-chain fatty acids. Another mechanism of fatty acid signaling in the intestine occurs via their conjugates. Among them, conjugates of unsaturated long chain fatty acids and acetate with 5-HT, N-acyl serotonins have recently emerged as mediators with immune-modulatory effects. In this review, novel findings in mechanisms and molecular players involved in intestinal fatty acid biology are highlighted and their potential relevance for EEC-mediated signaling to the pancreas, immune system, and brain is discussed.

High fat diet initiates rapid adaptation of the intestine

“…We confirmed this analysis by performing GIP and CCK ELISAs on mouse serum for all time points and saw an increasing trend of GIP by 7 Days HFD, whereas CCK levels slightly decreased at 3 Days HFD but remained relatively constant (Figure S5D). Moreover, expression of known fatty acid receptors, such as Ffar1, Ffar2, Ffar3, Ffar4, and Gpr119 33 remained relatively unchanged over the course of HFD (Figure S5E). Overall, EEC hormones and EEC fatty acid receptor transcriptional activity remained resilient during short term HFD and were not easily manipulated by fatty acid exposure.…”

Food‐grade titanium dioxide decreases hematocrit and hemoglobin and increases compulsive‐like behavior in male mice

“…On the other hand, recently, it was demonstrated that TiO 2 NPs could be contributing to alterations in animal behavior such as depression and anxiety (Tarlan et al, 2020;Younes et al, 2015); however, the via of administration was subcutaneously and the material used was entirely nanosized. We previously reported signs of anxiety in male mice exposed for 8 weeks using E171, which could be expected since dysbiosis and other gastric alterations are related to animal behavior through the gut-brain axis (Meijerink, 2021;Pinget et al, 2019;Scheepers et al, 2020) more than through TiO 2 NPs accumulation in the brain as it was proposed before (Tarlan et al, 2020). Additionally, blood alterations have been associated to behavioral disorders; for instance, decreased blood neutrophils, B12…”

Olfactory disfunction and diabetic complications in type 2 diabetic patients: a pilot study

“…The role of OR in these physiological processes is explained by the fact that G-protein-coupled receptor subfamilies of OR are present in many non-olfactory tissues such as liver, pancreas, heart, and gastrointestinal tract. Recent evidences show that intestinal OR are able to recognize nutrients such as short, medium, and branched chain fatty acids and to modulate glucagon-like-peptide-1 (GLP-1) and serotonin signaling by specialized enteroendocrine cells [ 40 ]. Similarly, taste receptors for bitter substances and free fatty acids are present in the gut and seem to exert an important role in glucose-dependent insulin secretion by modulating GLP-1 [ 41 , 42 ].…”