oa Noradrenaline-Induced Arteriolar Contractile Insensitivity And Collagen Deposition In Adipose Tissue Of Diabetic Patients

Background. Norepinephrine (NE) is a powerful regulator of various adipose metabolic and vascular functions, including vasoconstriction and tissue fibrosis. Recent data suggests that this may be through autocrine/paracrine effects on local resistance vessel function and morphology. Therefore, the aims of this study were to investigate in human sub-cutaneous and omental adipose tissue (SAT and OAT): 1) NE synthesis, 2) NE-mediated arteriolar vasoconstriction from non-diabetic versus diabetic obese subjects, 3) the induction of collagen genes and its deposition in the tissue. Methods and Results. AT from the abdominal subcutaneous and intra-abdominal greater omental depots was obtained during surgery (~5g each) and quickly transported in serum-free medium to the laboratory. The tissue was used for (i) histology and immunohistochemical analysis, (ii) dual wire myography for assessment of vascular reactivity, (iii) organ culture for assessment of NE release, (iv) protein extraction and NE ELISA, and (v) collagen gene type Iα1 mRNA expression. In the non-diabetic group: TH immunoreactivity, NE concentration, and maximal vasoconstriction were significantly higher in OAT compared to SAT (p<0.05). But arterioles from OAT showed lower NE sensitivity compared to SAT (Log EC50: SAT versus OAT, -7.3±0.6 versus -6.2±0.6, p<0.01). In the diabetic group: no significant depot differences were seen in NE synthesis or vasoconstriction. SAT arterioles showed significantly lower sensitivity to NE (10-8 M to 10-7.5 M, p<0.05) compared to non-diabetic group. Collagen deposition and gene expression were greater in OAT than SAT of non-diabetics, while levels were elevated but comparable within both depots of diabetic subjects. Conclusions. Elevated, chronic, local NE synthesis in OAT of non-diabetic subjects may desensitize NE-induced vasoconstriction, as greater NE synthesis in both depots of diabetic patients may explain the abolishment of the depot-specific differences and sensitivity to NE in obese patients. High NE levels may also explain greater collagen gene expression and its deposition in the OAT and in diabetes.