Kyungjoon Lim, Sandra L Burke and Geoffery A Head
Posters-Accepted Abstracts: Biol Syst Open Access
The obesity in women among child baring age is increasing and this has been reported to be parallel to the increase in obesity in general population. We determined the trans-generational 'programming' of leptin signalling in the central nervous system (CNS) following an initiation of a high fat diet (HFD) in mothers. Female New Zealand White rabbits were fed a high fat (13%) diet (mHFD) or a normal fat diet (mNFD) prior mating and during pregnancy. Offspring from mNFD rabbits were subdivided and fed a HFD for 10 days (mNFD10dHFD) to mimic adult hood obesity. All rabbits received an Intra Cerebro ventricular (ICV) catheter into the lateral ventricle and a recording electrode on the left renal nerve. Experiments were conducted in conscious rabbits and animals received increasing doses of melanocortin receptor antagonist (SHU9119), α-Melanocortin stimulating hormone (αMSH) and a single dose of Leptin antagonist via ICV. BP, HR and RSNA were measured. ICV SHU9119 reduced BP (-5.8±0.7 mmHg and -4.1±0.9 mmHg) and RSNA (-2.4±0.3 nu and -0.7±0.3 nu) in mHFD and mNFD10dHFD rabbits (P<0.001). Leptin antagonist reduced BP and RSNA only in mHFD rabbits (-2.1±0.5mmHg and -2.7nu, respectively). αMSH injection increased BP, HR and RSNA in both mHFD and mNFD10dHFD rabbits (P<0.05). Total % fat was increased (50%) in all rabbits that had HFD. Obesity during pregnancy 'programs' leptin signalling pathway in the CNS of the offspring during development. Leptin via activation of melanocortin pathway plays a key role in the CNS contributing to the pressor and tachycardic effects as well as renal sympathetic nerve activity in the pathophysiology of obesity.
