Abstract P130: The Influence of Maternal Obesity on Perivascular Adipose Tissue Function in Offspring

Objective: Maternal obesity pre-programs offspring to develop obesity and associated cardiovascular disease although the underlying mechanism is currently unknown. This study investigated the effect of maternal obesity on perivascular adipose tissue (PVAT) regulation of resistance artery tone. Design and method: 8 week old female SD rats were fed a 10% fat diet (controls) or 45% fat obesogenic diet (HFD) for 12 weeks before mating, then continued on their respective diets during pregnancy and lactation. Male offspring were provided with 10% fat diet until sacrifice at 12 weeks old. PVAT-intact or -denuded mesenteric arteries (250-300μm internal diameter) from offspring were mounted on a wire myograph. Cumulative concentration-response curves were constructed to the thromboxane A2 receptor agonist U46619 (10nM-3μM) ± 10μM A769662, an activator of AMP-activated kinase (AMPK) or 100μM L-NMMA, a nitric oxide synthase (NOS) inhibitor. Results: Body weight, systolic and diastolic blood pressure were significantly increased in HFD dams compared to age-matched controls (391±11 vs 348±12 g; 154±1 vs 145±1 mmHg; 116±1 vs 103±103 mmHg respectively) but no differences were observed between offspring. However, fat pads and insulin levels were increased in both HFD dams versus controls (13.4±1.6 vs 6.5±0.8 g; 1.18±0.09 vs 0.76±0.14 nmol/L respectively) and their offspring (7.2±0.3 vs 6.0±0.2 g; 0.56±0.15 vs 0.17±0.05 nmol/L respectively) versus controls. PVAT exerted an anti-contractile effect in artery segments from offspring of control dams (p<0.001), an effect which was lost in offspring of HFD dams. AMPK activation decreased contractility of both PVAT-denuded and -intact arteries from control offspring (p<0.01; p<0.0001 respectively, n=8); this effect was abolished in PVAT-intact vessels of offspring of HFD dams. Inhibition of NOS increased contractility of both PVAT-denuded and -intact arteries from control offspring (p<0.0001 and p<0.0001 respectively, n=8), revealing a contractile effect of PVAT in control offspring (p<0.01, n=8) but not in arteries from offspring of HFD dams. Conclusions: In summary, the diminished anti-contractile effects of PVAT in 12 week old offspring of HFD dams may be due to reduced AMPK and nitric oxide activity.