Disease relevance of Apoc3

• Targeted disruption of the apolipoprotein C-III gene in mice results in hypotriglyceridemia and protection from postprandial hypertriglyceridemia [1].
• 4. Remarkably, LDL modified by oxidation, treatment with phospholipase A2, or enrichment with apolipoprotein CIII, which are modifications associated with increased atherogenesis, is hydrolyzed readily by S-SMase at pH 7 [2].
• Moreover, the administration of fenofibrate not only resulted in liver hypertrophy and reduction in hepatic lipid accumulation, but also regulated the transcriptional expression of PPARalpha target genes, such as hepatic acyl-coenzyme A (CoA) oxidase and apolipoprotein C-III (apoC-III) [3].

High impact information on Apoc3

• Overexpression of plasma apolipoprotein CIII (apo CIII) causes hypertriglyceridemia in transgenic mice [4].
• Apolipoprotein CIII (Apo CIII) is a determinant of serum triglyceride metabolism [5].
• Bile acid treatment still repressed liver Apo CIII gene expression in hepatic HNF4alpha-deficient mice, suggesting an active rather than a competitive mechanism of Apo CIII repression by the FXR [5].
• Apolipoprotein CIII promotes Ca2+-dependent beta cell death in type 1 diabetes [6].
• The -700/-310 fragment of the apolipoprotein A-IV gene combined with the -890/-500 apolipoprotein C-III enhancer is sufficient to direct a pattern of gene expression similar to that for the endogenous apolipoprotein A-IV gene [7].

Chemical compound and disease context of Apoc3

• Apolipoprotein CIII deficiency prevents the development of hypertriglyceridemia in streptozotocin-induced diabetic mice [8].

Biological context of Apoc3

• A fat meal test showed that postprandial hypertriglyceridemia is abolished in homozygotes lacking ApoC-III [1].
• The mouse Apoc-3 gene is 2.2 kb in length and also consists of four exons and three introns [9].
• Apolipoprotein C-III deficiency accelerates triglyceride hydrolysis by lipoprotein lipase in wild-type and apoE knockout mice [10].
• ApoCIII (100 microg/mL), but not apoCI, apoCII or apoE, also increased THP-1 cell adhesion by 2.1+/-0.6-fold [11].
• Incubation of human primary hepatocytes and HepG2 cells with bile acids or the nonsteroidal synthetic FXR agonist GW4064 resulted in a dose-dependent down-regulation of Apo CIII gene expression [5].

Anatomical context of Apoc3

• Using gene targeting in embryonic stem cells, we have generated mice lacking apolipoprotein C-III (ApoC-III) [1].
• Apolipoprotein CIII in apolipoprotein B lipoproteins enhances the adhesion of human monocytic cells to endothelial cells [11].
• However, Apoc3 deficiency resulted in a significant increase in the uptake of TG-derived fatty acids from VLDL-like emulsion particles by white adipose tissue, indicating enhanced LPL activity [12].
• Apolipoprotein C-III can specifically bind to hepatic plasma membranes [13].

Associations of Apoc3 with chemical compounds

• These data indicate that ApoC-III modulates the catabolism of triglyceride-rich lipoproteins and plays a role in the postprandial management of triglycerides [1].
• Similar to apoE(+/+) apoC3(-/-) mice, apoE(-/-)apoC3(-/-) mice exhibited a marked reduction in VLDL cholesterol and TG, indicating that the mechanism(s) by which apoC-III deficiency exerts its lipid-lowering effect act independent of apoE [10].
• In addition, administration of fenofibrate reduced serum lipids and hepatic apolipoprotein C-III mRNA while increasing the mRNA of acyl-CoA oxidase in both groups of mice, however, these effects were more pronounced in OVX LDLR-null mice [14].
• Association between the SstI polymorphism of the apolipoprotein C-III gene, glucose intolerance and cardiovascular risk in renal transplant recipients [15].

Physical interactions of Apoc3

• This region contains a sequence similar to that found in the apolipoprotein CIII gene that has been shown to bind RXR alpha and the orphan nuclear receptor, ARP-1 [16].

Other interactions of Apoc3

• Characterization of the mouse apolipoprotein Apoa-1/Apoc-3 gene locus: genomic, mRNA, and protein sequences with comparisons to other species [9].

References