Endocrine Abstracts

The prevalence of obesity and related comorbidities is rising globally, with gastrointestinal systems heavily implicated in its pathophysiology. Obesity is an inflammatory state causing disruption of vessel structure and endothelial function. Nutrient-sensing mechanisms enable glucose uptake and secretion of anorectic hormones, potentially contributing to metabolic disease. Changes to postprandial blood flow in obesity are unclear and may be visualised using contrast-enhanced ultrasound (CEUS). This in-vivo study aimed to optimise and use CEUS to quantify the effect of glucose on duodenal blood flow in lean and obese mice. In a repeated measures experimental design, glucose solution (100% w/v, 5ml/kg) or vehicle control (5ml/kg) were administered by oral gavage (n = 11) or intraduodenal infusions (n = 7) into lean and diet-induced obese C57BL/6 mice. Ultrasound images were acquired using a microbubble contrast agent while under general anaesthesia. Microbubble intensity was representative of blood flow, which was measured by processing ultrasound acquisitions. CEUS enables non-invasive, non-ionising, visualisation of gut microvasculature to a resolution of 10um. In lean mice administered glucose or vehicle via oral gavage, there was a trend for glucose to evoke greater hyperaemia in the duodenum, whereas this trend was not evident in obese mice, potentially indicating a dampened nutrient response in obesity. Initial non-significant decreases in blood flow were observed following both infusions, suggesting either initial vasoconstriction, perhaps in response to shock, or effects of gut distension distorting the density of perfused blood vessels. However, overall, there were no significant differences found between the effects of glucose and vehicle control on duodenal hyperaemia. This study demonstrates the potential utility of CEUS as a method of visualising microvasculature and changes in blood flow to the gut. We demonstrate a potentially dampened glucose-sensing ability in obese mice and present a rationale for future research in understanding nutrient-sensing mechanisms and their role in metabolic disease.