AbstractsBiology & Animal Science

The role of hypothalamic neuropeptides in the development of obesity related hypertension

by Benjamin Barzel

Institution: Monash University
Department: Department of Anatomy and Developmental Biology
Year: 2015
Keywords: Obesity; Sympathetic nerve activity; Hypertension; Leptin
Record ID: 1046200
Full text PDF: http://arrow.monash.edu.au/hdl/1959.1/1158729


The relationship between body fat and blood pressure is such that relatively minor weight gains are associated with increases in mean arterial pressure (MAP). Whilst the relative risk of cardiovascular disease is greater once systolic and diastolic pressures reach 140/90 mmHg, respectively, it is important to note that there is no specific level of MAP at which disease develops and the correlation between MAP and risk of developing cardiovascular disease is strong, positive and continuous in nature (Carretero & Oparil, 2000). It is in this context that the increase in the prevalence of obesity must be examined. Obesity is now considered a global epidemic placing a considerable economic and health burden on society. Of major concern is the association between obesity and hypertension with some reports suggesting up to 78 % of newly diagnosed hypertension is attributable to obesity. The current thesis examines the effect of consuming a high fat diet (HFD) on metabolic profiles, haemodynamic rhythms and hypothalamic neurons pertinent to energy homeostasis and cardiovascular regulation. Experiments were conducted on New Zealand White rabbits given free access to either a normal fat diet (NFD) or a HFD for three weeks. The main advantage of short-term exposure to an obesogenic stimulus is removal of confounding variables associated with obesity. Therefore, early changes that are key to the development of hypertension can be detected more easily. An additional benefit of the model is that diet-induced obesity in rabbits manifests in a manner analogous to human obesity, namely increased adiposity, hypertension and augmented renal sympathetic nerve activity. Moreover, hypothalamic neuropeptides regulating energy and cardiovascular homeostasis as well as sympathetic tone in humans are well conserved evolutionarily and are thus at play in the rabbit. Recent evidence suggests specific lipid groups such as ceramides and cholesterol esters play a direct role in obesity-related pathologies. The haemodynamic and sympathetic response to the HFD develops within the firstfew days of consumption and it is possible that rapid changes in plasma lipid profiles accompany early weight gain and drive, at least initially, the observed hypertension. In addition to dyslipidaemia, hyperinsulinemia and hyperleptinaemia are known to exert a deleterious effect on cardiovascular health. Consequently, the first investigation described in Chapter 3 examined the effect of three week fat-feeding on metabolic profiles in the rabbit. Circulating insulin and glucose levels were increased within the first three days of the diet in HFD rabbits alone, remaining elevated at week 1 and returning to baseline thereafter. By contrast, plasma leptin levels remained unchanged in both dietary groups, increasing by week 3 in HFD rabbits alone. There was no dyslipidaemia in either NFD or HFD-fed rabbits. The main finding was that plasma insulin and leptin, but not dyslipidaemia, are likely involved in the genesis of hypertension in obesity albeit at different time…