Increased hypothalamic JNK expression contributes to reduction of insulin hypophagic effects during prolonged LPS exposure

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 649-675-Central Regulation of Appetite & Feeding/GI Regulatory Peptides
Bench to Bedside
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-658
Rodrigo Cesar Rorato1, Beatriz Carvalho Borges2, Ernane Torres Uchoa3, Paula Beatriz Marangon4, Jose Antunes-Rodrigues5 and Lucila Elias*6
1Univ de Sao Paulo, Ribeirao Preto, Brazil, 2Schl of Med, Ribeirao Preto, Ribeirao Preto SP, Brazil, 3University of Sao Paolo-FRMP, Ribeirao Preto-SP, Brazil, 4University of Sao Paulo, School of Medicine of Ribeirao Preto, Ribeirao Preto, Brazil, 5Univ of Sao Paulo Sch of Med, Ribeirao Preto SP, Brazil, 6Schl of Medcn of Ribeirao Pret, Ribeirao Preto, Brazil
It is well known that LPS increases JNK activity that in turn has been shown to contribute to the peripheral and central insulin resistance in diet-obese treated animals. On the other hand, repeated exposure to LPS leads to tolerance of hypophagic effect in response to endotoxemia. Therefore, in the present study we aimed to investigate if prolonged LPS treatment increases JNK expression in the hypothalamus and if the treatment with JNK inhibitor restores the hypophagic effects of insulin. For this purpose, rats were assigned into three different groups of treatment (ip, at 16:00h: saline once daily for 6 days (saline), saline once daily for 5 days and an injection of LPS at the 6th day (1LPS) and LPS once daily for 6 days (6LPS). On the day of the experiment, food was removed after treatments and two hours after (18:00h), rats were decapitated for brain collection for western blotting analyses of mediobasal hypothalamus. Another set of rats was i.c.v. cannulated and seven days after, on the day of the experiment, at 16:00h, food was withdrawn and the rats were weighted and treated with LPS (1LPS or 6LPS) or saline. At 16:30h the animals were treated with a JNK inhibitor (SP600125, 20µM/5µL, i.c.v.) or vehicle (0.2% DMSO in saline) and 30 minutes after they were treated with insulin (12µM/5µL, i.c.v.) or vehicle (saline). Food was reoffered at 18:00h and food consumptions and body weight were determined 2 and 14 hours after, respectively. We observed in 1LPS group, but not 6LPS group, an increased expression of phospho-Akt. On the other hand, rats treated with 6 doses of LPS showed higher expression of JNK and phospho-JNK. As expected, we observed a decreased food intake and body weight gain in 1LPS-treated rats compared with 6 saline and 6 LPS group. Insulin decreased food intake only in 6 saline group. Interestingly, we observed that JNK inhibitor treatment restored the hypophagic effects of insulin in 6 LPS treated animals. The present data suggest that repeated exposure to LPS is associated with a decrease of hypothalamic action of insulin on food intake, which is mediated by the increased phosphorylation of JNK.

Nothing to Disclose: RCR, BCB, ETU, PBM, JA, LE

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: FAPESP, CNPq, FAEPA