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. 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.
Departments of Physiology and Pharmacology, Texas A&M University, College Station, TX 77843-4466, USA.
Barbara P
BP
Atshaves
H Ross
HR
Payne
Avery L
AL
McIntosh
Shane E
SE
Tichy
David
D
Russell
Ann B
AB
Kier
Friedhelm
F
Schroeder
D000818:Animals; D001823:Body Composition / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism; D002995:Clofibric Acid / Q000494:pharmacology; D004041:Dietary Fats / Q000008:administration & dosage / Q000494:pharmacology*; D004951:Esterification; D005247:Feeding Behavior / Q000187:drug effects; D005260:Female; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood / Q000737:chemistry*; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D009929:Organ Size / Q000187:drug effects; D010836:Phytol / Q000008:administration & dosage / Q000494:pharmacology*; D011971:Receptors, Immunologic / Q000378:metabolism; D051116:Receptors, Scavenger; D012727:Sex Characteristics; D014280:Triglycerides / Q000378:metabolism
D002352:Carrier Proteins; D004041:Dietary Fats; D008055:Lipids; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D014280:Triglycerides; C072087:sterol carrier proteins; D010836:Phytol; D002995:Clofibric Acid