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188 The Influence of Maternal Obesity on Perivascular Adipose Tissue Function in Offspring
  1. Karolina Zaborska1,
  2. Gillian Edwards1,
  3. Clare Austin2,
  4. Mark Wareing1
  1. 1University of Manchester
  2. 2Edge Hill University

Abstract

Objective Maternal obesity pre-programmes offspring to develop obesity, glucose intolerance and associated cardiovascular disease later in life although the underlying mechanism is currently unknown. This study investigated the effect of a maternal high fat diet 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. PVAT-intact or -denuded mesenteric arteries from dams and pups (250–300 µm internal diameter) were mounted on a wire myograph. Cumulative concentration-response curves were constructed to thromboxane A2 receptor agonist U46619 (10 nM–3 µM) ± 10 µM A769662, an activator of AMP-activated kinase (AMPK), and/or 100 µM L-NMMA, a nitric oxide synthase (NOS) inhibitor.

Results Body weight (BW) and systolic (SBP) and diastolic (DBP) blood pressure were significantly increased in HFD dams (BW: p < 0.05, SBP: p < 0.001, DBP: p < 0.01) and their offspring at 24 weeks (BW <0.0001, SBP: p < 0.0001, DBP: p < 0.0001) compared to controls but no differences were observed in offspring at 12 weeks. PVAT exerted an anti-contractile effect in artery segments from control dams and their offspring at 12 and 24 weeks (p < 0.01, p < 0.001, p < 0.05), an effect which was lost in both dams fed HFD and their offspring. AMPK activation decreased contractility of both PVAT-denuded and intact control vessels in the presence and absence of a NOS inhibitor in control dams (p < 0.0001) and their offspring (p < 0.0001); this effect was decreased in PVAT-intact vessels of HFD dams and their offspring.

Conclusions In summary, the attenuated anti-contractile effects of PVAT in HFD dams and their offspring may be modulated by AMPK; however it is not totally dependent on nitric oxide release.

  • PVAT
  • Maternal obesity
  • AMPK

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