Abstract
The major net flux of cholesterol in the intact animal or human is from the peripheral organs to the liver. This flux is made up of cholesterol that is either synthesized in these peripheral tissues or taken up as lipoprotein cholesterol. This study investigates whether it is the concentration of apolipoprotein (apo) A-I or high density lipoprotein in the plasma that determines the magnitude of this flux or, alternatively, whether events within the peripheral cells them' selves regulate this important process. In mice that lack apoA-I and have very low concentrations of circulating high density lipoprotein, it was found that there was no accumulation of cholesterol in any peripheral organ so that the mean sterol concentration in these tissues was the same (2208 ± 29 mg/kg body weight) as in control mice (2176 ± 50 mg/kg). Furthermore, by measuring the rates of net cholesterol acquisition in the peripheral organs from de novo synthesis and uptake of low density lipoprotein, it was demonstrated that the magnitude of centripetal sterol movement from the peripheral organs to the liver was virtually identical in control animals (78 ± 5 mg/day per kg) and in those lacking apoA-I (72 ± 4 mg/day per kg). These studies indicate that the magnitude of net sterol flux through the body is not related to the concentration of high density lipoprotein or apolipoprotein A-I in the plasma, but is probably determined by intracellular processes in the peripheral organs that dictate the rate of movement of cholesterol from the endoplasmic reticulum to the plasma membrane.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2143-2149 |
| Number of pages | 7 |
| Journal | Journal of Lipid Research |
| Volume | 39 |
| Issue number | 11 |
| State | Published - Nov 1998 |
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Keywords
- Atherosclerosis
- Caveolae
- Endoplasmic reticulum
- Golgi
- Liver
- Low density lipoprotein
ASJC Scopus subject areas
- Endocrinology
Cite this
Centripetal cholesterol flux to the liver is dictated by events in the peripheral organs and not by the plasma high density lipoprotein or apolipoprotein A-I concentration. / Jolley, Christopher D.; Woollett, Laura A.; Turley, Stephen D.; Dietschy, John M.
In: Journal of Lipid Research, Vol. 39, No. 11, 11.1998, p. 2143-2149.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Centripetal cholesterol flux to the liver is dictated by events in the peripheral organs and not by the plasma high density lipoprotein or apolipoprotein A-I concentration
AU - Jolley, Christopher D.
AU - Woollett, Laura A.
AU - Turley, Stephen D.
AU - Dietschy, John M.
PY - 1998/11
Y1 - 1998/11
N2 - The major net flux of cholesterol in the intact animal or human is from the peripheral organs to the liver. This flux is made up of cholesterol that is either synthesized in these peripheral tissues or taken up as lipoprotein cholesterol. This study investigates whether it is the concentration of apolipoprotein (apo) A-I or high density lipoprotein in the plasma that determines the magnitude of this flux or, alternatively, whether events within the peripheral cells them' selves regulate this important process. In mice that lack apoA-I and have very low concentrations of circulating high density lipoprotein, it was found that there was no accumulation of cholesterol in any peripheral organ so that the mean sterol concentration in these tissues was the same (2208 ± 29 mg/kg body weight) as in control mice (2176 ± 50 mg/kg). Furthermore, by measuring the rates of net cholesterol acquisition in the peripheral organs from de novo synthesis and uptake of low density lipoprotein, it was demonstrated that the magnitude of centripetal sterol movement from the peripheral organs to the liver was virtually identical in control animals (78 ± 5 mg/day per kg) and in those lacking apoA-I (72 ± 4 mg/day per kg). These studies indicate that the magnitude of net sterol flux through the body is not related to the concentration of high density lipoprotein or apolipoprotein A-I in the plasma, but is probably determined by intracellular processes in the peripheral organs that dictate the rate of movement of cholesterol from the endoplasmic reticulum to the plasma membrane.
AB - The major net flux of cholesterol in the intact animal or human is from the peripheral organs to the liver. This flux is made up of cholesterol that is either synthesized in these peripheral tissues or taken up as lipoprotein cholesterol. This study investigates whether it is the concentration of apolipoprotein (apo) A-I or high density lipoprotein in the plasma that determines the magnitude of this flux or, alternatively, whether events within the peripheral cells them' selves regulate this important process. In mice that lack apoA-I and have very low concentrations of circulating high density lipoprotein, it was found that there was no accumulation of cholesterol in any peripheral organ so that the mean sterol concentration in these tissues was the same (2208 ± 29 mg/kg body weight) as in control mice (2176 ± 50 mg/kg). Furthermore, by measuring the rates of net cholesterol acquisition in the peripheral organs from de novo synthesis and uptake of low density lipoprotein, it was demonstrated that the magnitude of centripetal sterol movement from the peripheral organs to the liver was virtually identical in control animals (78 ± 5 mg/day per kg) and in those lacking apoA-I (72 ± 4 mg/day per kg). These studies indicate that the magnitude of net sterol flux through the body is not related to the concentration of high density lipoprotein or apolipoprotein A-I in the plasma, but is probably determined by intracellular processes in the peripheral organs that dictate the rate of movement of cholesterol from the endoplasmic reticulum to the plasma membrane.
KW - Atherosclerosis
KW - Caveolae
KW - Endoplasmic reticulum
KW - Golgi
KW - Liver
KW - Low density lipoprotein
UR - http://www.scopus.com/inward/record.url?scp=0031755081&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031755081&partnerID=8YFLogxK
M3 - Article
C2 - 9799800
AN - SCOPUS:0031755081
VL - 39
SP - 2143
EP - 2149
JO - Journal of Lipid Research
JF - Journal of Lipid Research
SN - 0022-2275
IS - 11
ER -