Abstract 413: Hypothalamic Leptin Signaling And Blood Pressure Regulation In Obese Rats
The main function of Leptin is to inform the individual's nutritional status to hypothalamus, which in turn regulate food intake and energy expenditure. Such actions are orchestrated by phosphorylation of ObRb receptor on tyrosine 985 and 1138, the latter is related to metabolism and Stat3 pathway. Recently, it was demonstrated that high serum levels of leptin, which is seen in DIO, correlates strongly with hypertension. On the other hand, obese individuals have resistance to metabolic actions of leptin (satiety and thermogenesis).
To investigate the molecular hypothalamic pathways that characterize the selective activity of leptin on the effect of blood pressure (BP) increase, adults Sprague Dawley rats were fed with standard diet (SD) or HFD for three months and were submitted to chronic ICV injection of leptin (2μg/day) or saline (2μl) for 10 days. BP, food intake and energy expenditure were assessed before and after treatment.
SD+leptin group had reduced food intake from 109,48±8,48 to 57,3±7,04 kcal / day, increased energy expenditure from 85,6±1,87 to 94,4±0,58 kcal/day/kg^0,75 and consequently weight reduction of 15,25±3,54 g (P <0.001 all) which did not occur in HFD+leptin. However, both SD and HFD group, leptin increased BP of 10.44±0.12% (from 103,7±0,7 to 114,8±0,8 mmHg) and 14.22±1.9% (from 118,6±1,3 to 132,2±1,5 mmHg), respectively.
As expected, obese animals had elevated levels of serum leptin when compared to SD group (SD: 2,24±0,38 ng/dl and HFD: 9,88±1,82 ng/dl, p<0,05). Additionally, we evaluate the main activated signal pathways by leptin in hypothalamus. SD+leptin group showed a significant increase in activity of Stat3, Akt and in MAPK expression. However, HFD+leptin group manifested an increase only on the expression of MAPK pathway. Both SD and HFD leptin-treated groups had higher ObRb tyr985 phosphorylation, which was not observed with the pObRb tyr1138. It was possible to see that ObRb tyr985 dependent pathway is responsive to leptin in SD and HFD, and ObRb tyr1138 as well as the related protein Stat3 and Akt are reduced in obese animals. Therefore, it may be suggested that in HFD-induced obesity hypothalamic pathway ObRb tyr985 / MAPK, unlike the other pathways, is not resistent and can be related to cardiovascular actions of leptin.
Author Disclosures: C.G.B. Silva: None. R.M. Marin: None. C.K. Katashima: None. F.K. Marcondes: None. M.J.A. Saad: None.
- © 2014 by American Heart Association, Inc.