Therefore, we speculate that ingestion of extensively hydrolyzed casein in mice facilitates reduction of glucose concentrations by increasing glycogen deposition, as well as by increasing conversion of glucose to D-glucuronic acid, which subsequently can lead to decreased deposition of lipids. Sulphate is, together with glutathione and taurine, synthesized from the sulphur amino acid cysteine. A major determinant of glutathione synthesis is the availability of cysteine, and since the level of free cysteine is kept low in the liver, it has been suggested that glutathione is a hepatic cysteine reservoir. In our previous paper we reported that hepatic concentrations of glutathione and taurine were increased in mice fed hydrolyzed casein, indicating higher cysteine availability relative to those of mice fed intact casein. If availability of cysteine was higher in hydrolyzed casein fed mice, it is also likely that more sulphate was synthesized from cysteine, which could explain the higher urinary excretion of sulphate conjugated compounds in the present study. Intake of extensively hydrolyzed casein diets increased fed-state plasma ��-hydroxybutyrate concentration, indicating an increased hepatic mitochondrial ketogenesis in mice. Mitochondrial respiration, including ketogenesis, is a major source of 4-IPP reactive oxygen species and may result in accumulation of oxidation products. We therefore measured the TBARS level in liver tissue and found a small but significantly higher level of TBARS in mice fed hydrolyzed casein compared with mice fed intact casein, indicating differences in oxidative stress between treatment groups. Regulatory pathways that may be induced by oxidative stress include the nuclear factor erythroid 2-related factor regulated pathways. Wen et al found that an increased level of Phase II metabolites in urine was caused by activation of the Nrf-2 pathway, and hence, in the present study, both increased oxidative stress and excretion of Phase II metabolites suggested that the Nrf-2 pathway was activated in mice receiving hydrolyzed casein. Furthermore, Nrf-2 has been shown to inhibit hepatic lipogenesis and an induction of Nrf-2 by high fat diets has been observed. Therefore, we measured expression of Nrf-2 target genes in livers from mice fed intact or hydrolyzed casein. 5-OMe-UDP trisodium salt However, no significantly different expression of genes encoding the antioxidant enzymes Hmox1 or Nqo1 H dehydrogenase, quinone 1), Me, the glutathione synthesizing enzymes Gclc, Gclm and Gss was observed between the mice fed the different diets. However, expression of the gene encoding the negative regulator of the p53 tumor suppressor, Mdm2 was down-regulated in mice fed hydrolyzed casein, suggesting that p53 regulated pathways were modulated by hydrolyzed casein feeding. Interestingly, p53 is involved in regulation of both glucose metabolism and oxidative stress response.