ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2015
Impact of SCP-2/SCP-x gene ablation and dietary cholesterol on hepatic lipid accumulation.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
- OAF Blocks SIAH1-Mediated Degradation of SCPX, a Therapeutic Strategy for MASLD.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Mitochondria-endoplasmic reticulum contact sites in hepatocytic senescence.Cellular & molecular biology letters · 2026Review
- Sterol carrier protein 2: A promising target in the pathogenesis of atherosclerosis.Genes & diseases · 2023Review
- Can Growth ofMarine drugs · 2022Article
- Anti-Obesity and Lipid Metabolism Effects ofJournal of microbiology and biotechnology · 2021Article
- The effect of high glucose on lipid metabolism in the human placenta.Scientific reports · 2019Article
- SCP2-mediated cholesterol membrane trafficking promotes the growth of pituitary adenomas via Hedgehog signaling activation.Journal of experimental & clinical cancer research : CR · 2019Article
- Dual targeting of Nur77 and AMPKα by isoalantolactone inhibits adipogenesis in vitro and decreases body fat mass in vivo.International journal of obesity (2005) · 2019Article
- Sterol Carrier Protein Inhibition-Based Control of Mosquito Vectors: Current Knowledge and Future Perspectives.The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale · 2019Review
- Scp-2/Scp-x ablation in Fabp1 null mice differentially impacts hepatic endocannabinoid level depending on dietary fat.Archives of biochemistry and biophysics · 2018Article
- Ablating both Fabp1 and Scp2/Scpx (TKO) induces hepatic phospholipid and cholesterol accumulation in high fat-fed mice.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2018Article
- Sex-dependent impact of Scp-2/Scp-x gene ablation on hepatic phytol metabolism.Archives of biochemistry and biophysics · 2017Article
- Loss of fatty acid binding protein-1 alters the hepatic endocannabinoid system response to a high-fat diet.Journal of lipid research · 2017Article
- Impact ofJournal of lipid research · 2017Article
- Effect of Fabp1/Scp-2/Scp-x Ablation on Whole Body and Hepatic Phenotype of Phytol-Fed Male Mice.Lipids · 2017Article
- Chemoproteomic Profiling of Acetanilide Herbicides Reveals Their Role in Inhibiting Fatty Acid Oxidation.ACS chemical biology · 2017Article
- Impact of dietary phytol on lipid metabolism in SCP2/SCPX/L-FABP null mice.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2017Article
- Fabp1 gene ablation inhibits high-fat diet-induced increase in brain endocannabinoids.Journal of neurochemistry · 2017Article
- Appropriate LDL-C-to-HDL-C Ratio Cutoffs for Categorization of Cardiovascular Disease Risk Factors among Uygur Adults in Xinjiang, China.International journal of environmental research and public health · 2016Article
- Sterol Carrier Protein-2, a Nonspecific Lipid-Transfer Protein, in Intracellular Cholesterol Trafficking in Testicular Leydig Cells.PloS one · 2016Article
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Authors and funding
8 authors at 1 institution in 1 country.
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Abstract
While a high-cholesterol diet induces hepatic steatosis, the role of intracellular sterol carrier protein-2/sterol carrier protein-x (SCP-2/SCP-x) proteins is unknown. We hypothesized that ablating SCP-2/SCP-x [double knockout (DKO)] would impact hepatic lipids (cholesterol and cholesteryl ester), especially in high-cholesterol-fed mice. DKO did not alter food consumption, and body weight (BW) gain decreased especially in females, concomitant with hepatic steatosis in females and less so in males. DKO-induced steatosis in control-fed wild-type (WT) mice was associated with 1) loss of SCP-2; 2) upregulation of liver fatty acid binding protein (L-FABP); 3) increased mRNA and/or protein levels of sterol regulatory element binding proteins (SREBP1 and SREBP2) as well as increased expression of target genes of cholesterol synthesis (Hmgcs1 and Hmgcr) and fatty acid synthesis (Acc1 and Fas); and 4) cholesteryl ester accumulation was also associated with increased acyl-CoA cholesterol acyltransferase-2 (ACAT2) in males. DKO exacerbated the high-cholesterol diet-induced hepatic cholesterol and glyceride accumulation, without further increasing SREBP1, SREBP2, or target genes. This exacerbation was associated both with loss of SCP-2 and concomitant downregulation of Ceh/Hsl, apolipoprotein B (ApoB), MTP, and/or L-FABP protein expression. DKO diminished the ability to secrete excess cholesterol into bile and oxidize cholesterol to bile acid for biliary excretion, especially in females. This suggested that SCP-2/SCP-x affects cholesterol transport to particular intracellular compartments, with ablation resulting in less to the endoplasmic reticulum for SREBP regulation, making more available for cholesteryl ester synthesis, for cholesteryl-ester storage in lipid droplets, and for bile salt synthesis and/or secretion. These alterations are significant findings, since they affect key processes in regulation of sterol metabolism.
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