title: Loss of L-FABP, SCP-2/SCP-x, or both induces hepatic lipid accumulation in female mice.
abstract: Although roles for both sterol carrier protein-2/sterol carrier protein-x (SCP-2/SCP-x) and liver fatty acid binding protein (L-FABP) have been proposed in hepatic lipid accumulation, individually ablating these genes has been complicated by concomitant alterations in the other gene product(s). For example, ablating SCP2/SCP-x induces upregulation of L-FABP in female mice. Therefore, the impact of ablating SCP-2/SCP-x (DKO) or L-FABP (LKO) individually or both together (TKO) was examined in female mice. Loss of SCP-2/SCP-x (DKO, TKO) more so than loss of L-FABP alone (LKO) increased hepatic total lipid and total cholesterol content, especially cholesteryl ester. Hepatic accumulation of nonesterified long chain fatty acids (LCFA) and phospholipids occurred only in DKO and TKO mice. Loss of SCP-2/SCP-x (DKO, TKO) increased serum total lipid primarily by increasing triglycerides. Altered hepatic level of proteins involved in cholesterol uptake, efflux, and/or secretion was observed, but did not compensate for the loss of L-FABP, SCP-2/SCP-x or both. However, synergistic responses were not seen with the combinatorial knock out animals-suggesting that inhibiting SCP-2/SCP-x is more correlative with hepatic dysfunction than L-FABP. The DKO- and TKO-induced hepatic accumulation of cholesterol and long chain fatty acids shared significant phenotypic similarities with non-alcoholic fatty liver disease (NAFLD).
authors.affiliation: Department of Physiology and Pharmacology, Texas A&M University, College Station, TX 77843-4466, United States.
authors.forename: Gregory G
authors.initials: GG
authors.lastname: Martin
authors.affiliation: Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, United States.
authors.forename: Barbara P
authors.initials: BP
authors.lastname: Atshaves
authors.affiliation: Department of Pathobiology, Texas A&M University, College Station, TX 77843-4467, United States.
authors.forename: Kerstin K
authors.initials: KK
authors.lastname: Landrock
authors.affiliation: Department of Pathobiology, Texas A&M University, College Station, TX 77843-4467, United States.
authors.forename: Danilo
authors.initials: D
authors.lastname: Landrock
authors.affiliation: Department of Physiology and Pharmacology, Texas A&M University, College Station, TX 77843-4466, United States.
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Schroeder
authors.affiliation: Department of Pathobiology, Texas A&M University, College Station, TX 77843-4467, United States. Electronic address: akier@cvm.tamu.edu.
authors.forename: Ann B
authors.initials: AB
authors.lastname: Kier
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D002788:Cholesterol Esters / Q000097:blood; D004195:Disease Models, Animal; D050556:Fatty Acid-Binding Proteins / Q000172:deficiency / Q000235:genetics*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D017353:Gene Deletion; D015870:Gene Expression; D050356:Lipid Metabolism / Q000235:genetics*; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D065626:Non-alcoholic Fatty Liver Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010743:Phospholipids / Q000097:blood; D014280:Triglycerides / Q000097:blood
chemical_list: D002352:Carrier Proteins; D002788:Cholesterol Esters; C493320:Fabp1 protein, mouse; D050556:Fatty Acid-Binding Proteins; D005230:Fatty Acids, Nonesterified; D010743:Phospholipids; D014280:Triglycerides; C072087:sterol carrier proteins; D002784:Cholesterol
keywords: Gene ablation; L-FABP; SCP-2; SCP-x