Developmental Origin Of Obesity Related Hypertension: Trans-generational Cardiovascular Impact Of High Fat Diet Feeding In Rabbits

We determined if exposed to a high fat diet (HFD) during development have a similar phenotype (changes in blood pressure (BP), heart rate (HR) and renal sympathetic nerve activity (RSNA)) in the offspring as adult obesity when consuming a HFD. New Zealand White breeder rabbits were placed on a normal or 13.5% high fat diet (HFD) from 3 weeks prior to mating, during pregnancy and during lactation. Maternal NFD (mNFD) offspring was divided to two groups and placed on HFD for 10 days (mNFD+10dHFD) to mimic adulthood obesity. Rabbit offspring were implanted with renal electrode to measure RSNA. At 18 weeks of age, rabbits were infused with alpha-melanocyte-stimulating hormone (αMSH, 10nmol), Leptin antagonist (100μg), SHU9119 (melanocortin 3 and 4 receptor antagonist, 0.0375nmol, 0.075nmol, 0.1875nmol and 0.375nmol) and vehicle intracerebroventricularly. There was no difference in baseline BP between all diet groups but baseline RSNA was increased in mHFD offspring (17.6 normalised unit (nu)) and mNFD+10dHFD offspring (10.7 nu) when compared to mNFD offspring (5.6 nu). αMSH injection increased BP (from 68 to 75mmHG, p<0.01) in mNFD+10dHFD offspring and HR was increased (from 159bpm to 246bpm, p<0.01) in maternal HFD offspring. When SHU9119 was injected, there was a reduction in BP in both maternal HFD (from 71 to 65mmHG, p<0.001) and mNFD+10dHFD (from 78 to 72mmHG, p<0.01) offspring. Leptin antagonist had no effect on BP in all diet groups but RSNA was reduced (29% reduction from 13 normalised unit) in mHFD offspring. The phenotype of developmental obesity shows similar characteristics of adulthood obesity where the elevation of RSNA induced by HFD is predominantly mediated by increased sensitivity of the leptin signalling pathway.