A Study Of Changes In Energy Metabolism In Young Cysteine Dioxygenase (Cdo1) Knockout Mice In Response To High Dietary Fat With Or Without Taurine Supplementation.

Abstract

Cysteine homeostasis is dependent on the regulation of cysteine dioxygenase (CDO) in response to sulfur amino acid intake. Knockout of the murine Cdo1 gene results in elevated cysteine levels, severe impairment in ability to synthesize taurine, and an increased catabolism of cysteine to H2S. For unknown reasons, knockout Cdo1 mice are obesity-resistant and insulin sensitive when fed a high-fat diet. In order to understand the underlying physiologic cause for this phenotype, we studied mice after only a short exposure to the high-fat diet so that results would not be confounded by the consequences of obesity and insulin resistance. In our study, we maintained wild-type and Cdo1-/- C57BL/6 mice on a basal, high-fat, or taurine supplemented high-fat diet from the age of ~41.5 days to ~64.5 days (total 23 days). We found that Cdo1-/-mice ate more feed and gained weight faster than wild-type mice, though they had similar energy expenditure and activity levels. Cdo1-/-mice showed early signs of abnormal fat metabolism as indicated by their higher serum triglyceride and acyl-carnitine levels concurrent with higher SCD1 and ACC1 liver proteins compared to wild-type mice. Cdo1-/-mice also showed lower serum leptin levels, a phenomenon also observed in older Cdo1-/-mice, which may explain why Cdo1-/-mice are resistant to fat deposition later in life. Future studies are needed to determine the link between a lack of the Cdo1 gene and low leptin levels.