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Effect of SCP-x gene ablation on branched-chain fatty acid metabolism.
Am J Physiol Gastrointest Liver Physiol. 2007 Mar; 292(3):G939-51.AJ

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.

Authors+Show Affiliations

Department of Physiology and Pharmacology, Texas A and M University, College Station, Texas 77843, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

17068117

Citation

Atshaves, Barbara P., et al. "Effect of SCP-x Gene Ablation On Branched-chain Fatty Acid Metabolism." American Journal of Physiology. Gastrointestinal and Liver Physiology, vol. 292, no. 3, 2007, pp. G939-51.
Atshaves BP, McIntosh AL, Landrock D, et al. Effect of SCP-x gene ablation on branched-chain fatty acid metabolism. Am J Physiol Gastrointest Liver Physiol. 2007;292(3):G939-51.
Atshaves, B. P., McIntosh, A. L., Landrock, D., Payne, H. R., Mackie, J. T., Maeda, N., Ball, J., Schroeder, F., & 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), G939-51.
Atshaves BP, et al. Effect of SCP-x Gene Ablation On Branched-chain Fatty Acid Metabolism. Am J Physiol Gastrointest Liver Physiol. 2007;292(3):G939-51. PubMed PMID: 17068117.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of SCP-x gene ablation on branched-chain fatty acid metabolism. AU - Atshaves,Barbara P, AU - McIntosh,Avery L, AU - Landrock,Danilo, AU - Payne,H Ross, AU - Mackie,John T, AU - Maeda,Nobuyo, AU - Ball,Judith, AU - Schroeder,Friedhelm, AU - Kier,Ann B, Y1 - 2006/10/26/ PY - 2006/10/28/pubmed PY - 2007/4/25/medline PY - 2006/10/28/entrez SP - G939 EP - 51 JF - American journal of physiology. Gastrointestinal and liver physiology JO - Am J Physiol Gastrointest Liver Physiol VL - 292 IS - 3 N2 - 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. SN - 0193-1857 UR - https://www.unboundmedicine.com/medline/citation/17068117/Effect_of_SCP_x_gene_ablation_on_branched_chain_fatty_acid_metabolism_ L2 - https://journals.physiology.org/doi/10.1152/ajpgi.00308.2006?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -