Dysfunction of human subcutaneous fat arterioles in obesity alone or obesity associated with Type 2 diabetes

Abstract

The aim of the present study was to examine the effects of obesity alone and obesity associated with Type 2 diabetes on the structure, vascular reactivity and response to insulin of isolated human subcutaneous fat arterioles; these effects were correlated with the expression of insulin signalling proteins. Periumbilical subcutaneous adipose tissue was explanted during surgery, small arterioles (internal diameter 220 ± 40 μm) were dissected out and investigated by electron microscopy, myography and immunoblotting. Compared with the subcutaneous arterioles of lean subjects, obesity activated the endothelium, enhanced the accumulation of collagen within vascular wall and increased the sensitivity of adrenergic response; obesity also diminished eNOS (endothelial NO synthase) protein expression, NO production, and endothelium-dependent and insulin-induced vasodilatation, as well as the protein expression of both IRS (insulin receptor substrates)-1 and IRS-2 and of the downstream molecules in the insulin signalling pathway, such as PI3K (phosphoinositide 3-kinase), phospho-Akt and Akt. When obesity was associated with Type 2 diabetes, these changes were significantly augmented. In conclusion, obesity alone or obesity associated with Type 2 diabetes alters human periumbilical adipose tissue arterioles in terms of structure, function and biochemsitry, including diminished eNOS expression and reduced levels of IRS-1, IRS-2, PI3K and Akt in the insulin signalling pathway.

Reduced Expression of Prostacyclin Synthase and Nitric Oxide Synthase in Subcutaneous Arteries of Type 2 Diabetic Patients

“…Reduction in eNOS protein expression in diabetes may lead to the loss of vasodilator responses. This conclusion is supported by the reduced endothelium-dependent vasodilatation observed in subcutaneous arterioles of patients with type-2 diabetes (Georgescu et al 2011). This reduction was associated with decreased eNOS protein expression and reduced endothelial NO pro- duction (Georgescu et al 2011) and altered mitochondrial function (Kizhakekuttu et al 2012).…”

“…Imbalance in the production of these factors is a characteristic of endothelial dysfunction, one key event in the development of microvascular complications in human and animal models of diabetes (Pieper 1998;De Vriese et al 2000;Matsumoto et al 2005). Indeed, endothelium-dependent vasodilatation is impaired in arterioles of humans with type-2 diabetes (Georgescu et al 2011;Kizhakekuttu et al 2012). …”

“…Thus, the present study aims to determine the expression levels of eNOS, COX-1, COX-2, PGIS and IP receptor proteins in subcutaneous arteries of diabetic patients compared to non-diabetic controls. Information gained may help to elucidate the roles of these proteins in the development of endothelial dysfunction in the human diabetic microcirculation (Szerafin et al 2006;Georgescu et al 2011). …”

Childhood obesity: a life-long health risk

“…The function of the vasculature, particularly endothelium-dependent vasomotion, reflects quite well the overall health status of the arterial system [62] . Human obesity, characterized by accumulation of ectopic (particularly visceral) fat [63] , is associated with abnormal endothelium-dependent vasomotion and enhanced contractility to endothelin-1 [64,65] . Accordingly, a reduction in energy intake [66] or reduction in body weight [67] improves vascular function in obese patients.…”

The anti-obesogenic effects of nitric oxide.

“…rodents [158][159][160][161][162] . Factors associated with obesity and diabetes including increased shear stress, lysophosphatidylcholine, oxidized LDL, insulin and decreased ability to exercise can also regulate eNOS expression [163][164][165][166][167] .…”