Sexually dimorphic metabolism of branched-chain lipids in C57BL/6J mice

Despite the importance of branched chain lipid oxidation in detoxification, almost nothing is known regarding factors regulating peroxisomal uptake, targeting, and metabolism. One peroxisomal protein, sterol carrier protein-x (SCP-x), is thought to catalyze a key thiolytic step in branched chain lipid oxidation. When mice with substantially lower hepatic levels of SCP-x were tested for susceptibility to dietary stress with phytol (a phytanic acid precursor and peroxisome proliferator), livers of phytol-fed female but not male mice i) accumulated phytol metabolites (phytanic acid, pristanic acid, and Delta-2,3-pristanic acid); ii) exhibited decreased fat tissue mass and increased liver mass/ body mass; iii) displayed signs of histopathological lesions in the liver; and iv) demonstrated significant alterations in hepatic lipid distributions. Moreover, both male and female mice exhibited phytol-induced peroxisomal proliferation, as demonstrated by liver morphology and upregulation of the peroxisomal protein catalase. In addition, levels of liver fatty acid binding protein, along with SCP-2 and SCP-x, increased, suggesting upregulation mediated by phytanic acid, a known ligand agonist of the peroxisomal proliferator-activated receptor alpha-jlr In summary, the present work establishes a role for SCP-x in branched chain lipid catabolism and demonstrates a sexual dimorphic response to phytol, a precursor of phytanic acid, in lipid parameters and hepatotoxicity.-Atshaves, B. P., H. R. Payne, A. L. McIn-tosh, S. E. Tichy, D. Russell, A. B. Kier, and F. Schroeder. Sexually dimorphic metabolism of branched-chain lipids in C57BL/6j mice. J Lipid Res. 2004. 45: 812-830.