Microvascular blood flow and metabolic networking in the gut-pancreas-liver axis

The body responds to nutrient intake through the coordination of the activity of a number of different organs, and particularly the gut, pancreas and liver. These organs act together to efficiently process the nutrients from the food we eat, allowing us to build and repair our bodies, and providing energy. We know that these organs need to work in concert to be effective, but our understanding of how they are interlinked is currently limited. Blood flow in these organs reflects their activity. We have developed an imaging approach using ultrasound that will allow us to investigate the blood flow in these organs non-invasively and at a very detailed level. We intend to optimise these methods to look at the effects different foods have on the blood flow in the gut, pancreas and brain, and to investigate which components of these foods drive the different effects on metabolism. We will also look at how the activity of these organs can become dysfunctional after a long time on a high fat diet, or as the body ages. Understanding the normal coordinated functioning of the gut, pancreas and liver, and how it changes in response to challenges, will identify targets for diets or drugs in the future to try and maintain a healthy metabolism. Developing this imaging approach will also reduce the number of animals used for these kinds of study in the future.

The co-ordinated activity of the gut, pancreas and liver is critical for normal metabolic function and the maintenance of health.

This project will investigate microvascular blood flow and metabolic activity in the gut-pancreas-liver axis, determine how dietary components co-ordinate this axis, and identify how diet and ageing can chronically alter its activity to drive negative effects on health. We will use cutting edge ultrasound imaging techniques to investigate how microvascular blood flow in these organs reflects co-ordinated metabolic activity.

Hypothesis: Co-ordinated changes in the gut, pancreatic and hepatic microvasculature reflect metabolic responses to ingested nutrients and are disrupted by high fat diet intake and ageing.

Aims:

1) Optimise CEUS protocols for the visualisation of microvascular blood flow in the mouse gut, pancreas and liver.

2) Determine the acute effects of specific dietary macronutrients on microvascular blood flow in these tissues, gut hormone release and glucose homeostasis.

3) Investigate the mechanisms responsible for the effects of diet observed on microvascular blood flow and metabolism.

4) Identify the chronic effects of a high fat diet and ageing on microvascular blood flow and metabolism in these tissues.

This multidisciplinary project will map the dynamic activity of the gut-pancreas-liver axis with unprecedented temporal and spatial resolution, and establish new methodologies for studying tissue function non-invasively. Understanding how the metabolic functions of the gut, liver and pancreas are coordinated, and how dysfunction can occur with diet and ageing, will identify new approaches for maintaining metabolic health.