Abstracts

Rationale: Ketogenic diet (KD) is a high-fat low carbohydrate diet that exerts anticonvulsive properties. The underlying mechanisms of this diet remain unclear. PPAR activation by high fat component of KD has been suggested. PPAR pathway activation may lead to anti-inflammatory effects. Here, we try to assess the anti-inflammatory effect of KD using a model of LPS-induced fever in rats. We also explored inflammatory response and PPAR pathways in the studied groups. Methods: Male Wistar rats (200-260 g) were housed 4 per cage on an alternating 12:12 light-dark cycle with day. Two groups are studied: Ketogenic diet group (n=8) that received KD during 14 days (Ketocal, SHS, Liverpool, UK) and control group (n=8) that received standard diet during 14 days. Both group received an i.p. injection of 50 g/kg of LPS. The body temperature was assessed each 15min during 4 hours. The temperature room was 20-22 C. Serum, liver and brain sample were analyzed in the two groups. The expression of both PPAR? and PPAR? were analyzed in the brain and the liver from additional animals (n=8 in each group). Results: Hyperthermia induced by LPS appeared 2h after LPS injection in control group. The body temperature remains below 38.5 C at all time points in the KD group. A significant difference between the groups was observed from 2.5h after LPS injection to the end of the experiment (Figure). Looking at PPAR expression by PCR, we observed in the liver an increase of both PPAR? and PPAR? expression in the KD group while there was no significant difference in the brain. Cytokine profile is under investigation. Conclusions: KD has anti-inflammatory properties. It is now well established that inflammation may contribute to seizure precipitation. The anti-inflammatory effect of KD may be involved in the anticonvulsive effect. PPAR pathways may be explained this anti-inflammatory properties.