Augmented capacity for peripheral serotonin release in human obesity.

Background/objectives: Evidence from animal studies highlights an important role for serotonin (5-HT), derived from gut enterochromaffin (EC) cells, in regulating hepatic glucose production, lipolysis and thermogenesis, and promoting obesity and dysglycemia. Evidence in humans is limited, although elevated plasma 5-HT concentrations are linked to obesity.

Subjects/methods: We assessed (i) plasma 5-HT concentrations before and during intraduodenal glucose infusion (4 kcal/min for 30 min) in non-diabetic obese (BMI 44 ± 4 kg/m, N = 14) and control (BMI 24 ± 1 kg/m, N = 10) subjects, (ii) functional activation of duodenal EC cells (immunodetection of phospho-extracellular related-kinase, pERK) in response to glucose, and in separate subjects, (iii) expression of tryptophan hydroxylase-1 (TPH1) in duodenum and colon (N = 39), and (iv) 5-HT content in primary EC cells from these regions (N = 85).

Plasma endocannabinoid levels in lean, overweight, and obese humans: relationships to intestinal permeability markers, inflammation, and incretin secretion.

Intestinal production of endocannabinoid and oleoylethanolamide (OEA) is impaired in high-fat diet/obese rodents, leading to reduced satiety. Such diets also alter the intestinal microbiome in association with enhanced intestinal permeability and inflammation; however, little is known of these effects in humans. This study aimed to 1) evaluate effects of lipid on plasma anandamide (AEA), 2-arachidonyl- sn-glycerol (2-AG), and OEA in humans; and 2) examine relationships to intestinal permeability, inflammation markers, and incretin hormone secretion.

Duodenal fatty acid sensor and transporter expression following acute fat exposure in healthy lean humans.

Background & Aims: Free fatty acids (FFAs) and their derivatives are detected by G-protein coupled receptors (GPRs) on enteroendocrine cells, with specific transporters on enterocytes. It is unknown whether acute fat exposure affects FFA sensors/transporters, and whether this relates to hormone secretion and habitual fat intake.

Methods: We studied 20 healthy participants (10M, 10F; BMI: 22 ± 1 kg/m; age: 28 ± 2 years), after an overnight fast, on 2 separate days.

Oral and intestinal sweet and fat tasting: impact of receptor polymorphisms and dietary modulation for metabolic disease.

The human body has evolved with a disposition for nutrient storage, allowing for periods of irregular food availability and famine. In contrast, the modern diet is characterized by excessive consumption of fats and sugars, resulting in a surge in the rates of obesity and type 2 diabetes. Although these metabolic disorders arise from a complex interaction of genetic, social, and environmental factors, evidence now points to fundamental changes in nutrient metabolism at the cellular level contributing to the underlying pathology.

The effects of critical illness on intestinal glucose sensing, transporters, and absorption.

Objectives: Providing effective enteral nutrition is important during critical illness. In health, glucose is absorbed from the small intestine via sodium-dependent glucose transporter-1 and glucose transporter-2, which may both be regulated by intestinal sweet taste receptors. We evaluated the effect of critical illness on glucose absorption and expression of intestinal sodium-dependent glucose transporter-1, glucose transporter-2, and sweet taste receptors in humans and mice.