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Event: 115
Key Event Title
Increase, FA Influx
Short name
Biological Context
Level of Biological Organization |
---|
Cellular |
Cell term
Cell term |
---|
hepatocyte |
Organ term
Key Event Components
Process | Object | Action |
---|---|---|
positive regulation of fatty acid transport | fatty acid | increased |
Key Event Overview
AOPs Including This Key Event
AOP Name | Role of event in AOP | Point of Contact | Author Status | OECD Status |
---|---|---|---|---|
LXR Activation to Liver Steatosis | KeyEvent | Marina Goumenou (send email) | Not under active development | |
PXR activation leads to liver steatosis | KeyEvent | John Frisch (send email) | Under development: Not open for comment. Do not cite |
Taxonomic Applicability
Term | Scientific Term | Evidence | Link |
---|---|---|---|
Vertebrates | Vertebrates | High | NCBI |
Life Stages
Life stage | Evidence |
---|---|
Adult | High |
Juvenile | Moderate |
Sex Applicability
Term | Evidence |
---|---|
Unspecific | High |
Key Event Description
Fat influx to the liver is usually increased under condition like obesity. Free fatty acids (FFA) increase in blood leads to an increase of FFA uptake in the liver. Especially the long chain fatty acids (LCFAs) are translocated across the plasma membrane, reassembled to triglycerides and stored in lipid droplets causing hepatic steatosis [1].
As mentioned above CD36 has consistently been shown to be expressed at the plasma membrane and to enhance LCFA uptake upon over-expression [2], [3].
How It Is Measured or Detected
Increases in fatty acid influx are generally measured by increases in triglycerides, fatty acids, cholesterols, and similar compounds in cells. In addition, assessment is generally made for plasma membrane stability and/or gene expression increases with genes associated with influx, to associate the increase in fatty acid compounds with influx rather than other pathways (ex. synthesis).
Domain of Applicability
Life Stage: Applies to all life stages with a liver. Older individuals are more likely to manifest this adverse outcome pathway (adults > juveniles) due to accumulation of triglycerides.
Sex: Applies to both males and females.
Taxonomic: Appears to be present broadly in vertebrates, with most representative studies in mammals (humans, lab mice, lab rats).
References
- ↑ Amacher 2011 - Amacher D.E., The mechanistic basis for the induction of hepatic steatosis by xenobiotics, Expert Opinion on Drug Metabolism and Toxicology, 7 (No 8), 949-965, 2011
- ↑ Baranowski 2008 - Baranowski, Biological role of liver X receptors, Journal of Physiology and Pharmacology, 59 (Suppl 7), 31–55, 2008
- ↑ Su & Abumrad 2009 - Su X., Abumrad N.A., Cellular fatty acid uptake: a pathway under construction. Trends Endocrinol. Metab., 20 (No 2), 72-77, 2009