Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCA240

Poster Communications

Acute vs chronic administration of leptin in obese rats: effects on blood pressure, sympathetic activity and glucose homeostasis

M. J. Ribeiro1, C. S. Prego1, J. F. Sacramento1, J. P. Cunha-Guimarães1, S. V. Conde1

1. CEDOC, NOVA Medical School, Faculdade Ciências Médicas, Lisboa, Portugal, Lisboa, Portugal.

Leptin is an adipocyte hormone essential in energy homeostasis regulation acting centrally and peripherally. In addition to its generalized sympathoexcitatory activity that influence cardiovascular function leptin is involved in glucose homeostasis. This hormone is one of the key players involved in the development of obesity induced-hypertension via sympathetic activation; however there is some controversy regarding the acute vs chronic leptin affects on BP (1). Chronic intravenous and carotid infusion of leptin increases BP in conscious rats (2) an effect that could be mediated in part by the carotid body (CB). Recently, we have reported that leptin might be involved in the trigger of CB (3), a peripheral chemo and metabolic sensor, contributing to the genesis of insulin resistance and hypertension in metabolic syndrome animals via sympathetic nervous system (SNS) activation (4). Also, it is known that chronic leptin administration improves insulin sensitivity and normalizes plasma glucose in type 2 diabetes rats, independent of energy intake via peripheral and possibility centrally mediated actions (5). Therefore, we aimed to evaluate the effect of acute vs leptin administration on mean arterial pressure (MAP), SNS activity and glucose homeostasis in a metabolic syndrome animal model. Experiments were performed in male Wistar rats (8-9 weeks) fed during 3 weeks with a standard (CTR) or 60% lipid-rich (HF) diet. Acute leptin administration (90-360 ng/ml, i.v.) was evaluated in MAP and in SNS activity. Chronic leptin administration was tested on control and HF animals submitted to 7 days of leptin administration. Additionally, the contribution of CB to leptin effects was tested by making the same experiments in animals submitted to carotid sinus nerve resection prior to HF diet. Leptin effects were evaluated on MAP, SNS activity, caloric intake, temperature as well as on insulin sensitivity and glucose tolerance. HF diet increased MAP by 32.87% (control=81.76 mmHg; HF= 108.63mmHg; p<0.05) and SNS activity by 22.54% (control=0.8154;HF=1 burst/sec; p<0.05 ), compared by Student's t-test. Acute leptin administration increased in a dose-dependent manner MAP in CTR animals (90ng/ml by 2.83% and 360 ng/ml by 27.67) an effect that was blunted in HF animals (180 ng/ml by 0.29% and 260 ng/ml by 2.34%). Also, in CTR group SNS activity increased with leptin administration (90 ng/ml by 6.05%; 180 ng/ml by 23.05%; 270ng /ml by 27.08%, (p<0.05) and 360 ng/ml by 17.30). We can conclude that the effect of leptin in promoting SNS activation and increase in MAP is blunted in obese animals probably via an already developed leptin resistance. Knowing that the CB is involved in the genesis of obesity induced-hypertension we suggest that leptin action of the CB can be target to ameliorate this pathological feature.

Where applicable, experiments conform with Society ethical requirements