The ketogenic diet (KD), characterized by high fat and low carbohydrate and protein contents, has been proposed to be beneficial in children with epilepsy disorders not helped by conventional anti-epileptic drug treatment. Weight loss and inadequate growth is an important drawback of this diet and metabolic causes are not well characterized. The aim of this study was to examine body weight variation during KD feeding for 6 wk of Wistar rats; fat mass and adipocyte cytosolic phosphoenolpyruvate carboxykinase (PEPCK) activity were also observed. PEPCK activity was determined based on the [H(14)CO(3) (-)]-oxaloacetate exchange reaction. KD-fed rats gained weight at a less rapid rate than normal-fed rats, but with a significant increment in fat mass. The fat mass/body weight ratio already differed between ketogenic and control rats after the first week of treatment, and was 2.4 x higher in ketogenic rats. The visceral lipogenesis was supported by an increment in adipocyte PEPCK, aiming to provide glycerol 3-phosphate to triacylglycerol synthesis and this fat accumulation was accompanied by glucose intolerance. These data contribute to our understanding of the metabolic effects of the KD in adipose tissue and liver and suggest some potential risks of this diet, particularly visceral fat accumulation.