Award details

Nutritional regulation of adipose tissue blood flow in humans: dietary neural and structural determinants

Reference	BB/D008123/1
Principal Investigator / Supervisor	Professor Keith Frayn
Co-Investigators / Co-Supervisors
Institution	University of Oxford
Department	RDM OCDEM
Funding type	Research
Value (£)	331,001
Status	Completed
Type	Research Grant
Start date	01/02/2006
End date	31/07/2008
Duration	30 months

Abstract

In healthy people, blood flow through subcutaneous adipose tissue responds rapidly and markedly to nutrient intake. There are parallels between classical measurements of endothelial function such as flow-mediated vasodilatation (FMD) and the adipose tissue blood flow response to nutrients. Impairment of FMD is associated with insulin resistance and increased risk of coronary heart disease. Impaired adipose tissue blood flow responsiveness to nutrients is also associated with insulin resistance. FMD is NO-mediated; NO also plays a major role in regulation of adipose tissue blood flow. In this project, we will use novel methodologies for assessing regulation of adipose tissue blood flow in humans to test a number of hypotheses. First, we will test whether there are indeed parallels between FMD and adipose tissue blood flow responsiveness. This will be done in a cross-sectional study of healthy men and women. Secondly, we will test the hypothesis that adipose tissue blood flow regulation depends upon the balance of sympathetic and parasympathetic nervous system activity, which we will assess by heart rate variability measurements. During assessment of adipose tissue blood flow we will use the technique of local microinfusion of isoprenaline and propranolol to assess beta-adrenergic responsiveness of blood flow. Thirdly, we will test whether adipose tissue blood flow responsiveness can be modified in parallel with FMD by appropriate dietary intervention. Healthy men and women will follow the Dietary Approaches to Stop Hypertension (DASH) diet for 30 days with assessments of vascular function at beginning and end. A control group will maintain their usual diet. In parallel with these in vivo studies, we will examine structural correlates ex vivo at a cellular and molecular level in adipose tissue biopsies taken from the participants. We will assess adipocyte size, capillarity and the protein and mRNA expression of components we expect to be involved in blood flow regulation.

Summary

Fat is stored on the wall of the abdomen and under the skin in other places on the body. Blood flows through these deposits of fat. We discovered recently that the flow of blood to the fat deposits can increase a lot just after a meal. But in some people the blood flow does not increase. These are people who are at increased risk of developing heart disease as judged from blood samples. This is similar to observations made on blood flowing through the big blood vessels in the arm. If you stop the blood flowing through the arm with a tourniquet for a few minutes, normally the blood then rushes back at an increased rate. It is already known that if someone's arm blood flow is 'unresponsive' when challenged in this way, then that person is at increased risk of developing heart disease. In this project we want to find out what makes the blood flow in fat increase after a meal, why it doesn't do that in some people, and whether we can alter that by changing someone's diet to a 'healthier' pattern. We think the nervous system probably regulates the blood flow and we will test whether that is so, and what is different in the people whose blood flow doesn't respond to meals. Then we can see if the nervous system responses are changed by a healthier diet. We will also use a syringe and needle to take little samples of the fatty tissue for examination under a microscope to try to understand what is different about the fat deposits in someone whose blood flow doesn't respond to meals. In the long term, this research may help explain why the functioning of blood vessels is related to risk of heart disease, and may help us to guide people with increased risk of heart disease towards healthier diets.

Committee	Closed Committee - Agri-food (AF)
Research Topics	Ageing, Diet and Health, Neuroscience and Behaviour
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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