Role of adipose tissue microvascular blood flow in Type 2 diabetes

Microvascular blood flow is important to deliver key nutrients (e.g. oxygen, lipids and glucose) and hormones (e.g. insulin) to and remove waste products from adipose tissue. Total adipose tissue blood flow (ATBF) increases after a meal, and this response is impaired in obesity and type 2 diabetes (T2D). Microvascular blood flow is more important than total blood flow for nutrient exchange in many tissues, however it is not known whether microvascular blood flow in adipose tissue is altered by meals or T2D. Chronic exercise training improves microvascular blood flow in skeletal muscle of people with T2D. Whether adipose tissue microvascular responses are similarly improved following exercise training in people with T2D is unknown. The overarching goal of the current thesis is to characterise microvascular ATBF responses to a meal in healthy and T2D subjects, and determine whether these responses are altered by chronic exercise training. The first aim characterised adipose tissue microvascular blood flow responses in the post-prandial state in healthy people. Adipose tissue microvascular blood flow was measured by contrast-enhanced ultrasound (CEU) at baseline and 1-hour after a mixed meal challenge or an oral glucose challenge (OGC). Adipose tissue microvascular blood volume (MBV) and microvascular blood flow (MBF) increased to a similar extent with both challenges. This increased microvascular perfusion of adipose tissue may improve delivery of key nutrients (e.g. glucose and lipid) from the meal for storage in adipose tissue. The second aim investigated whether people with T2D have an impairment in adipose tissue microvascular responsiveness following an OGC, and whether systemic inflammation or the metabolic syndrome is associated with an adipose tissue microvascular-linked phenotype. Adipose tissue MBV and MBF post-OGC were markedly impaired in T2D when compared to healthy controls. These impaired microvascular responses in adipose tissue were associated with obesity, insulin resistance, hyperglycaemia and dyslipidaemia, but not systemic inflammation. The final aim determined whether chronic exercise training restores adipose tissue microvascular blood flow in people with T2D. Adipose tissue microvascular blood flow was measured by CEU before and after six-weeks (three days per week) of a fully supervised resistance training program. Insulin sensitivity, glycaemic regulation, circulating lipids and body composition were all improved in people with T2D following resistance training. However, these favourable cardio-metabolic outcomes were not associated with a paralleled improvement in adipose tissue MBV and/or MBF. Collectively, this thesis has demonstrated that a mixed meal or an OGC induces both MBF and MBV increases in adipose tissue in healthy but not people with T2D, and these impairments are not restored by six weeks of exercise training. The dissociation of impaired adipose microvascular blood flow from inflammation, but association with body fat, glycaemic response and lipid handling provides clues about the role of adipose tissue microvascular blood flow in metabolic derangements associated with T2D. In particular, changes in adipose tissue microvascular blood flow in obesity/T2D may affect lipid deposition prior to altering adipose tissue hypoxia and inflammation.