Effect of SCP-x gene ablation on branched-chain fatty acid metabolism

Atshaves, B. P., McIntosh, A. L., Landrock, D., Payne, H. R., Mackie, J. T., Maeda, N., Ball, J., Schroeder, F. and Kier, A. B. (2007) Effect of SCP-x gene ablation on branched-chain fatty acid metabolism. American Journal of Physiology - Gastrointestinal and Liver Physiology, 292 3: G939-G951. doi:10.1152/ajpgi.00308.2006


Author Atshaves, B. P.
McIntosh, A. L.
Landrock, D.
Payne, H. R.
Mackie, J. T.
Maeda, N.
Ball, J.
Schroeder, F.
Kier, A. B.
Title Effect of SCP-x gene ablation on branched-chain fatty acid metabolism
Journal name American Journal of Physiology - Gastrointestinal and Liver Physiology   Check publisher's open access policy
ISSN 1522-1547
Publication date 2007-03
Year available 2007
Sub-type Article (original research)
DOI 10.1152/ajpgi.00308.2006
Volume 292
Issue 3
Start page G939
End page G951
Total pages 13
Place of publication Bethesda, MD
Publisher American Physiological Society
Language eng
Subject 070709 Veterinary Pathology
Abstract Despite the importance of peroxisomal oxidation in branched-chain lipid (phytol, cholesterol) detoxification, little is known regarding the factors regulating the peroxisomal uptake, targeting, and metabolism of these lipids. Although in vitro data suggest that sterol carrier protein (SCP)-x plays an important role in branched-chain lipid oxidation, the full physiological significance of this peroxisomal enzyme is not completely clear. To begin to resolve this issue, SCP-x-null mice were generated by gene ablation of SCP-x from the SCP-x/SCP-2 gene and fed a phytol-enriched diet to characterize the effects of lipid overload in a system with minimal 2/3-oxoacyl-CoA thiolytic activity. It was shown that SCP-x gene ablation 1) did not result in reduced expression of SCP-2 (previously thought to be derived in considerable part by posttranslational cleavage of SCP-x); 2) increased expression levels of key enzymes involved in {alpha}- and beta-oxidation; and 3) altered lipid distributions, leading to decreased hepatic fatty acid and triglyceride levels. In response to dietary phytol, lack of SCP-x resulted in 1) accumulation of phytol metabolites despite substantial upregulation of hepatic peroxisomal and mitochondrial enzymes; 2) reduced body weight gain and fat tissue mass; and 3) hepatic enlargement, increased mottling, and necrosis. In summary, the present work with SCP-x gene-ablated mice demonstrates, for the first time, a direct physiological relationship between lack of SCP-x and decreased ability to metabolize branched-chain lipids.
Keyword sterol carrier protein x
gene targeting
sterol carrier protein 2
liver fatty acid binding protein
phytanic acid
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Veterinary Science Publications
 
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