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

Journal of Lipid Research

Ann B. Kier¹  Avery L. McIntosh¹  H. Ross Payne²  David Russell²  Barbara P. Atshaves³  Friedhelm Schroeder³  Shane E. Tichy³ 

[1] Chemistry, Texas A&M University, College Station, TX 77843-4466;Pathobiology, Texas A&M University, College Station, TX 77843-4466;Departments of Physiology and Pharmacology, Texas A&M University, College Station, TX 77843-4466;

关键词: sterol carrier protein-2;    sterol carrier protein-x;    liver fatty acid binding protein;    peroxisome proliferator-activated receptor α;    peroxisome;    phytanic acid;   

DOI  :  

来源: DOAJ

【 摘 要 】

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 Δ-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 α.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.

【 授权许可】

Unknown