API
Event: 807
Key Event Title
Short name
Decreased, cholesterolBiological Context
| Level of Biological Organization |
|---|
| Cellular |
Cell term
Organ term
| Organ term |
|---|
| liver |
Key Event Components
| Process | Object | Action |
|---|---|---|
| cholesterol biosynthetic process | cholesterol | decreased |
Key Event Overview
AOPs Including This Key Event
| AOP Name | Role of event in AOP |
|---|---|
| HMGCR inhibition to male fertility | KeyEvent |
Stressors
Taxonomic Applicability
| Term | Scientific Term | Evidence | Link | |
|---|---|---|---|---|
| Vertebrates | Vertebrates | High | NCBI |
Life Stages
Sex Applicability
| Term | Evidence |
|---|---|
| Male | High |
| Female | High |
Key Event Description
Most cholesterol synthesis occurs within the endoplasmic reticulum of hepatic cells. First, acetyl-CoA is converted to HMG-CoA via HMG-CoA synthase. Next, HMG-CoA is converted to mevalonate via HMG-CoA reductase. Several other steps follow, but this is the rate-limiting step of cholesterol synthesis. Statin drugs inhibit HMG-CoA reductase to reduce cholesterol. Cholesterol synthesis may also occur to a limited extent in steroidogenic cells where it’s used to produce steroid hormones (Azhar et al. 2007)
How It Is Measured or Detected
Commerical assay kits are available for measuring cholesterol
Domain of Applicability
Cholesterol is not synthesized in plants (Behrman and Gopalan 2005)
Evidence for Perturbation by Stressor
Gemfibrozil
Juvenile female rainbow trout have decreased cholesterol (including total, HDL, LDL, & VLDL) after exposure to gemfibrozil (Prindiville et al. 2011)
Male and female zebrafish fed gemfibrozil alone or in combination with atorvastatin have decreased cholesterol (Al-Habsi et al. 2016)
Bezafibrate
Adult male zebrafish fed bezafibrate have decreased cholesterol (Velasco-Santamaría et al. 2011)
Clofibrate
Feeding grass carp either a high-fat or high-carbohydrate diet causes increases in total cholesterol, HDL, and LDL. Clofibrate reduces the high cholesterol levels caused by these diets to levels similar to controls (Guo et al. 2015)
Fenofibrate
Feeding fenofibrate to grass carp on a high fat diet causes a decrease in cholesterol, LDL, body weight, and whole-body lipid content (Du et al. 2008)
Atorvastatin
Male and female zebrafish fed atorvastatin alone or in combination with gemfibrozil have decreased whole-bodycholesterol (Al-Habsi et al. 2016)