Arnold von Eckardstein Lipoprotein-Metabolism Lipoprotein ...
Arnold von Eckardstein Lipoprotein-Metabolism Lipoprotein ...
Arnold von Eckardstein Lipoprotein-Metabolism Lipoprotein ...
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<strong>Arnold</strong> <strong>von</strong> <strong>Eckardstein</strong><br />
Institute of Clinical Chemistry,<br />
University and University Hospital Zürich,<br />
Switzerland<br />
<strong>Lipoprotein</strong>-<strong>Metabolism</strong><br />
Alter,<br />
Geschlecht,<br />
KHK-Ereignisse<br />
in der Eigenanamnese<br />
und/oder<br />
Familienanamnese,<br />
Genetische Veranlagung<br />
Unveränderliche<br />
Risikofaktoren<br />
KHK-Risikofaktoren<br />
Rauchen,<br />
Unausgewogene<br />
Ernährung<br />
(reich an Energie<br />
und Fett,<br />
arm an Vitaminen<br />
und Fasern)<br />
Bewegungsmangel,<br />
Streß<br />
Diabetes mellitus,<br />
niedriges HDL-C,<br />
Hypercholesterinämie,<br />
Erhöhte Triglyzeridwerte,<br />
Erhöhter Blutdruck,<br />
Hyperhomocysteinämie<br />
Fettleibigkeit<br />
CRP<br />
Lebensführung<br />
Modifizierbare<br />
Risikofaktoren<br />
200<br />
150<br />
100<br />
50<br />
0<br />
200<br />
150<br />
100<br />
50<br />
0<br />
Lipidstoffwechselstörungen und<br />
koronares Risiko<br />
(PROCAM: 4951 Männer, 35-65 J., 325 Herzinfarkte i. 10 J.)<br />
KHK-Ereignisse/1000 in 10 Jahren<br />
23<br />
45 51<br />
< 5,0 5,0 - 5,5 5,5- 6,0 6,0 - 6,7 > 6,7<br />
81<br />
Cholesterin-Quintile (mmol/l)<br />
KHK-Ereignisse/1000 in 10 Jahren<br />
39<br />
52 59<br />
78<br />
149<br />
119<br />
< 1,0 1,00 - 1,30 1,31-1,72 1,73-2,40 > 2,40<br />
Triglyzerid-Quintile (mmol/l)<br />
200<br />
150<br />
100<br />
50<br />
0<br />
200<br />
150<br />
100<br />
50<br />
0<br />
KHK-Ereignisse/1000 in 10 Jahren<br />
21<br />
38<br />
54<br />
78<br />
151<br />
< 3,08 3,08 - 3,60 3,61 - 4,07 4,08 - 4,71 > 4,71<br />
130<br />
LDL-Cholesterin-Quintile (mmol/l)<br />
KHK-Ereignisse/1000 in 10 Jahren<br />
50<br />
< 0,95 0,95-1,08 1,09-1,23 1,24-1,42 3,5 mmol/l, 5 Jahre Follow-up)<br />
Basis-Situation Statin Plazebo NNT *<br />
(N = 10269) (N = 10267)<br />
vorheriger MI 1007 1255 10<br />
andere KHK-Manifestation 452 597 12,5<br />
keine KHK, aber<br />
cerebrale VK 182 215 15<br />
periphere VK 332 427 15<br />
Diabetes mellitus 279 369 15<br />
Alle Ereignisse 2042 2606 13<br />
*: NNT = Anzahl 5 Jahre lang zu behandelnder Patienten, um 1 Ereignis zu verhüten<br />
<strong>Lipoprotein</strong>-<strong>Metabolism</strong><br />
Principal Structure of <strong>Lipoprotein</strong>s<br />
apolipopoprotein<br />
‣ Structure of lipoproteins<br />
‣ <strong>Metabolism</strong> of lipoproteins<br />
‣ Regulation of lipoprotein metabolism<br />
Hydrophobic<br />
core<br />
Hydrophilic<br />
surface<br />
cholesterol<br />
cholesterol ester<br />
phospholipid<br />
triglyceride
density<br />
(g/ml)<br />
0,95 -<br />
1,006 -<br />
IDL<br />
<strong>Lipoprotein</strong>s<br />
VLDL<br />
chylomicron<br />
remnants<br />
Kernlipide:<br />
.<br />
Chylomicron<br />
core<br />
lipids:<br />
TG C<br />
90% 10%<br />
75% 25%<br />
<strong>Lipoprotein</strong>s<br />
chylo- VLDL IDL LDL HDL<br />
microns<br />
density < 0.995 < 1.006 < 1.019 < 1.063 < 1.21<br />
(kg/L)<br />
LDL<br />
HDL<br />
...<br />
. . . . .<br />
1,20 -<br />
< 12 18 25 25 80 80 1200<br />
Stoke‘s diameter (nm)<br />
20% 80%<br />
20% 80%<br />
% lipid 98-99 90-95 84-88 74-78 < 55<br />
major B-48 B-100 B-100 B-100 A-I, A-II<br />
apolipo- A-IV, A-I Cs, E Cs, E A-IV<br />
proteins (Cs, E) (A-I) Cs, E<br />
Apolipoproteins<br />
apo <strong>Lipoprotein</strong> specific functions<br />
A I HDL (CM) LCAT-activation,<br />
A II HDL HDL-receptor (ABCA1) binding<br />
A IV Chylomicrons, (HDL)<br />
B-48 Chylomicrons, Chylomicron formation<br />
B-100 VLDL, IDL, HDL VLDL-, LDL- formation,<br />
LDL-receptor binding<br />
<strong>Lipoprotein</strong>-<strong>Metabolism</strong><br />
‣ Structure of lipoproteins<br />
‣ <strong>Metabolism</strong> of lipoproteins<br />
C I<br />
blocks hepatic Lp-receptors,<br />
C II Chylomicrons, lipoprotein lipase activation<br />
C III VLDL, IDL, HDL blocks hepatic Lp-receptors,<br />
E Chylomicrons, receptor ligand<br />
CM-Remnants<br />
VLDL, IDL, HDL<br />
<strong>Lipoprotein</strong>s as Transporters<br />
adipocytes<br />
dietary triglycerides (TG)<br />
and phospholipids (PL)<br />
60-100 g/day<br />
energy metabolism<br />
Lp<br />
dietary cholesterol<br />
0.2-0.5g/day<br />
cholesterol<br />
biosynthesis<br />
cellular metabolism<br />
(steroid hormones,<br />
membranes)<br />
bile production<br />
(bile salts, cholesterol)<br />
Cholesterol Transport<br />
Uptake<br />
0.2 - 0.5 g/day<br />
chylo<br />
microns<br />
bile acid pool<br />
2-3g<br />
(10x circulation)<br />
ca. 1g/day<br />
excretion<br />
ca. 0.8g/day<br />
free cholesterol, bile acids<br />
TG- and PLbiosynthesis<br />
chylomicronremnants<br />
production<br />
0.5 - 1g/day in<br />
liver & peripheral cells<br />
VLDL<br />
IDL<br />
Cholesterol in<br />
blood ca. 5g<br />
HDL<br />
LDL<br />
consumption<br />
0.5 - 0.6 g/day<br />
e.g. steroid hormones
⊃<br />
Transport of exogenous/dietary lipids<br />
(chylomicron metabolism)<br />
Transport of endogenous lipids<br />
(VLDL / LDL metabolism)<br />
TG PL<br />
lipid<br />
C<br />
micelle<br />
Bile acids<br />
LDL-Clearance<br />
TG<br />
C<br />
PL<br />
adipocyte<br />
intestinal<br />
brush border cell<br />
capillary endothelium<br />
TG<br />
FFA FFA<br />
<strong>Lipoprotein</strong>lipase<br />
TG<br />
C<br />
CMR<br />
CMR<br />
Energy metabolism<br />
PL<br />
hepatocyte<br />
chylomicron<br />
remnant<br />
hepatocytes<br />
adipocyte<br />
VLDL<br />
VLDL<br />
C<br />
TG<br />
LDL<br />
PL<br />
chylomicron<br />
via lymph<br />
chylomicron<br />
LDLreceptor<br />
IDL<br />
capillary endothelium<br />
TG<br />
FFA FFA<br />
<strong>Lipoprotein</strong>lipase<br />
LDL<br />
IDL<br />
Energy metabolism<br />
LDL<br />
C<br />
TG PL<br />
peripheral<br />
cells<br />
i-BABP<br />
bile<br />
acid<br />
cholesterol and<br />
phytosterols<br />
(from diet and bile)<br />
i-BAT<br />
+<br />
bile<br />
acids<br />
micellar<br />
sterols<br />
Intestinal<br />
lumen<br />
Intestinal resorption<br />
of sterols<br />
ABCG5<br />
ABCG8<br />
SR-B1,<br />
CD36?<br />
cholesterol<br />
MTP<br />
enterocyte<br />
CM<br />
chylus<br />
(lymph)<br />
CM<br />
Structural Models of ABCG5 and ABCG8<br />
(Lu et al. Trends Endocrinol Metab. 2001;12:314-20)<br />
ABCG5<br />
ABCG8<br />
out<br />
Membrane<br />
in<br />
A<br />
N<br />
E145Q<br />
C<br />
R419H/P<br />
R408X<br />
R389H<br />
B<br />
Y<br />
⊃ ⊃<br />
⊃<br />
R243X<br />
Y<br />
Q604E<br />
Y<br />
⊃ ⊃ ⊃ ⊃<br />
C<br />
A632V<br />
L596R<br />
G575R<br />
G574E/R<br />
L572P<br />
Y658X<br />
C<br />
B<br />
L596R<br />
W536X<br />
R543S<br />
Q172X<br />
N<br />
R412X<br />
L501P T400K<br />
W361X<br />
R263E<br />
P231T<br />
C<br />
R184X<br />
A<br />
R121X<br />
VLDL synthesis<br />
Lipolysis of triglyceride-rich lipoproteins<br />
endoplasmatic<br />
reticulum<br />
MTP<br />
TG<br />
TG<br />
TG<br />
TG<br />
apoB-100<br />
nucleus<br />
E<br />
VLDL<br />
E<br />
E<br />
VLDL<br />
E<br />
E<br />
VLDL<br />
E<br />
endothelium<br />
CM<br />
(VLDL)<br />
TG<br />
TG TG<br />
C-II<br />
LPL<br />
E<br />
LPL<br />
surface-remnants (HDL-precursor)<br />
E<br />
CMR<br />
(IDL)<br />
to liver<br />
Vesikel<br />
sinus<br />
lumen<br />
MTP =<br />
microsomal triglyceride<br />
transfer protein<br />
endothelium<br />
adipocytes<br />
fatty acids<br />
(+ DAG, MAG)<br />
myocytes
E<br />
Catabolism of lipoprotein remnants<br />
LDL<br />
LDL<br />
Regulation of the cellular cholesterol<br />
homeostasis by the LDL-receptor<br />
LDL-receptor<br />
LDL<br />
1. HMG CoA-reductase<br />
E<br />
CMR<br />
IDL<br />
CMR<br />
IDL<br />
LDL-receptor<br />
CM-receptor (LRP)<br />
CMR<br />
IDL<br />
CMR<br />
IDL<br />
E<br />
E<br />
lysosome<br />
FFA<br />
AA<br />
chol<br />
apoB<br />
Cholesterol<br />
(ester)<br />
2. ACAT<br />
Endosomes<br />
LDLreceptor<br />
Cholesterylester<br />
droplets<br />
3. LDL-receptor<br />
CMR<br />
IDL<br />
E<br />
cholesterol & bile acids<br />
synthesis of<br />
lipoproteins<br />
& membranes<br />
LDL-binding internalisation lysosomal<br />
hydrolysis<br />
regulation<br />
Catabolism of LDL<br />
Normal: LDL-receptor pathway<br />
disturbed: scavenger pathway<br />
Cholesterol homeostasis<br />
in macrophage foam cells<br />
LDL<br />
LDL<br />
oxLDL<br />
SR-BI<br />
HDL<br />
LDL<br />
LDL<br />
Ox<br />
LDL<br />
Ox<br />
LDL<br />
SR-A<br />
Cholesterol<br />
ABCA1<br />
ApoE<br />
ApoA-I<br />
LDL<br />
LpE<br />
liver<br />
macrophage<br />
liver<br />
macrophage<br />
Anti-atherogenicity of HDL<br />
(ATVB 2001, 20: 13-27; Atherosclerosis 2002, 161: 1-16)<br />
blood<br />
LDL<br />
endothelium<br />
inhibits<br />
thrombus<br />
formation<br />
Inhibits LDL<br />
oxidation<br />
HDL<br />
arterial wall<br />
HDL<br />
inhibits<br />
monocyte immigration<br />
modulates apoptosis and function<br />
of endothelial cells<br />
LDL<br />
macrophage<br />
Ox-<br />
LDL<br />
HDL<br />
monocyte<br />
ApoA-I<br />
stimulates<br />
cholesterol<br />
efflux<br />
foam<br />
cell<br />
modulates apoptosis, proliferation and function of SMCs<br />
HDL<br />
preβ-<br />
HDL<br />
TGRL<br />
LPL<br />
ABCA1<br />
Hepatic and peripheral cells<br />
HDL <strong>Metabolism</strong><br />
intestine<br />
apoA-I<br />
preβ-<br />
HDL<br />
liver<br />
lipid transfer<br />
protein transfer
A<br />
Structural Model<br />
of ABCA1/apoA-I<br />
interaction<br />
out<br />
Membran<br />
e<br />
in<br />
Y<br />
Y<br />
N<br />
ABCA1<br />
Y<br />
⊃<br />
⊃<br />
⊃<br />
Y<br />
Y<br />
⊃<br />
⊃ ⊃ ⊃<br />
⊃<br />
⊃<br />
⊃<br />
⊃<br />
C<br />
S S<br />
residues<br />
220-232<br />
⊃<br />
Y<br />
B<br />
N<br />
apoA-I<br />
Y<br />
Y<br />
A<br />
B<br />
C<br />
in<br />
ABCA1, Lipid- Efflux and Maturation of HDL<br />
TGN<br />
ABCA1<br />
apoA-I<br />
plasmamembrane<br />
preβ-<br />
HDL<br />
LCAT α-HDL<br />
Cholesterin<br />
out<br />
Phospholipid<br />
HDL <strong>Metabolism</strong><br />
Lecithin:cholesterol-acyltransferase<br />
O<br />
intestine<br />
LPL<br />
TGRL<br />
apoA-I<br />
SR-BI ABCA1<br />
Hepatic and peripheral cells<br />
liver<br />
O<br />
O unsaturated fatty acid<br />
O<br />
O<br />
CH 3 +<br />
+<br />
O P O N CH 3<br />
O - CH 3<br />
phosphatidylcholine<br />
(= lecithin)<br />
O<br />
OH<br />
LCAT (+ apoA-I)<br />
cholesterol<br />
O<br />
preβ-<br />
HDL<br />
HDL 3<br />
LCAT<br />
lipid transfer<br />
protein transfer<br />
OH<br />
O<br />
O P<br />
O -<br />
O<br />
lysolecithin<br />
CH 3<br />
+<br />
N CH 3<br />
CH 3<br />
+<br />
O<br />
O unsaturated fatty acid<br />
cholesterol ester<br />
Scavenger receptor B1 (SR-B1) and<br />
lecithin:cholesterol-acyltransferase (LCAT)<br />
HDL <strong>Metabolism</strong><br />
TGRL<br />
LPL<br />
intestine<br />
liver<br />
α-Helices<br />
of apo A-I<br />
phospholipid<br />
cholesterol<br />
cholesterol-ester<br />
SR-B1<br />
LCAT<br />
LCAT<br />
α-HDL<br />
SR-BI ABCA1<br />
Hepatic and peripheral cells<br />
apoA-I<br />
cellmembrane<br />
preβ-<br />
HDL<br />
HDL 2<br />
LCAT<br />
HDL PLTP 3<br />
LCAT<br />
surface<br />
remnants<br />
lipid transfer<br />
protein transfer
TGRL<br />
LPL<br />
SR-BI ABCA1<br />
Hepatic and peripheral cells<br />
HDL <strong>Metabolism</strong><br />
intestine<br />
apoA-I<br />
preβ-<br />
HDL<br />
LCAT<br />
liver<br />
HDL 3<br />
PLTP<br />
HDL 2 CETP<br />
CETP<br />
LCAT<br />
lipid transfer<br />
protein transfer<br />
LDL-receptor<br />
surface<br />
remnants<br />
(V)LDL<br />
TGRL<br />
LPL<br />
SR-BI ABCA1<br />
Hepatic and peripheral cells<br />
HDL <strong>Metabolism</strong><br />
intestine<br />
apoA-I<br />
preβ-<br />
HDL<br />
LCAT<br />
liver<br />
selective<br />
uptake<br />
(V)LDL<br />
(SR-BI,<br />
HL)<br />
HDL 2 CETP<br />
HL,<br />
SR-B1,<br />
LCAT<br />
CETP<br />
HDL PLTP 3<br />
lipid transfer<br />
protein transfer<br />
LDL-receptor<br />
surface<br />
remnants<br />
TGRL<br />
LPL<br />
SR-BI ABCA1<br />
Hepatic and peripheral cells<br />
HDL <strong>Metabolism</strong><br />
intestine<br />
apoA-I<br />
preβ-<br />
HDL<br />
LCAT<br />
lipid transfer<br />
protein transfer<br />
LDL-receptor<br />
surface<br />
remnants<br />
Biliary lipid secretion<br />
ABCG5<br />
ABCG8<br />
BSEP<br />
bile<br />
acids<br />
MDR3<br />
SR-BI<br />
cholesterol bile acids phosphatidylcholine<br />
CYP7A<br />
CYP8A<br />
HDL<br />
CM<br />
R<br />
LDL<br />
LDLR<br />
TGRL<br />
LPL<br />
SR-BI ABCA1<br />
Hepatic and peripheral cells<br />
Drugs 2003: 43: 1907-1943<br />
kidney<br />
HDL <strong>Metabolism</strong><br />
ABCG5 & ABCG8<br />
CYP7α, BSEP<br />
intestine<br />
liver<br />
cubilin<br />
apoA-I<br />
liver particle<br />
uptake<br />
(β-chain<br />
selective of ATPsynthase)<br />
uptake<br />
(V)LDL<br />
(SR-BI,<br />
HL)<br />
HDL 2 CETP<br />
HL, EL,<br />
SR-B1,<br />
LCAT<br />
CETP<br />
HDL PLTP 3<br />
cholesterol<br />
phosphatidylcholine<br />
preβ-<br />
HDL<br />
LCAT<br />
particle<br />
uptake<br />
(β-chain<br />
selective of ATPsynthase)<br />
uptake<br />
(SR-BI,<br />
HL)<br />
HDL 2 CETP<br />
HL, EL,<br />
SR-B1,<br />
LCAT<br />
CETP<br />
HDL PLTP 3<br />
lipid transfer<br />
protein transfer<br />
LDL-receptor<br />
surface<br />
remnants<br />
(V)LDL<br />
<strong>Lipoprotein</strong>-<strong>Metabolism</strong><br />
‣ Structure of lipoproteins<br />
‣ <strong>Metabolism</strong> of lipoproteins<br />
‣ Regulation of lipoprotein metabolism
Cholesterol:<br />
Too little or too much?<br />
Too little:<br />
- Smith-Lemli-Opitz-syndrome<br />
- Pelger-Huet-Syndrome<br />
- abetalipoproteinemia<br />
Too much/wrong place:<br />
- familial hypercholesterolemia<br />
- sitosterolemia<br />
- cerebrotendinous xanthomatosis<br />
- Tangier disease<br />
- arteriosclerosis (CHD, stroke)<br />
- vascular dementia<br />
- Alzheimer‘s disease?<br />
HO<br />
<strong>Metabolism</strong> and function of<br />
cholesterol and its metabolites<br />
vitamin D<br />
- gene regulation<br />
steroid hormones<br />
acetyl-CoA + acetylacetyl-CoA<br />
negative<br />
feedback<br />
regulation<br />
HMG-CoA<br />
mevalonate<br />
Cholesterol<br />
oxysterols<br />
- membrane component<br />
- regulation of cell<br />
-growth&<br />
differentiation,<br />
- transport,<br />
- function<br />
bile acids<br />
- gene regulation - gene regulation - gene regulation<br />
- detergens<br />
Regulation of gene expression by<br />
sterol-regulatory element binding proteins (SREBPs)<br />
Cholesterol inhibits the activation of SREBPs<br />
bHLH<br />
N<br />
C<br />
SREBP<br />
Reg.<br />
C<br />
N<br />
C<br />
SREBP<br />
Reg.<br />
C<br />
+ cholesterol<br />
bHLH<br />
bHLH<br />
S2P<br />
WD<br />
SCAP<br />
N<br />
bHLH<br />
WD<br />
SCAP<br />
N<br />
gene with SRE<br />
gene with SRE<br />
S1P<br />
ER lumen<br />
mRNA<br />
ER lumen<br />
(LDL-rec., HMG-CoA-red.)<br />
+ SREBP2<br />
HMG-<br />
CoA-<br />
Red.<br />
HDL<br />
SR-BI<br />
+<br />
CMR<br />
SREBP2<br />
LDL<br />
HMG-<br />
CoA-<br />
Red.<br />
SR-BI<br />
HDL<br />
CMR<br />
LDL<br />
Chol.<br />
FAS<br />
FAT<br />
VLDL<br />
LDLR<br />
+ SREBP2<br />
VLDL<br />
Chol.<br />
FAS<br />
FAT<br />
+ SREBP1<br />
LXRα<br />
VLDL<br />
LDLR<br />
VLDL
Enhanced cholesterol efflux from<br />
macrophage foam cells by LXRα activation<br />
oxLDL<br />
SR-BI<br />
HDL<br />
Regulation of ABCA1 expression<br />
by oxysterols and retinoids<br />
retinoids<br />
oxysterols<br />
SR-A<br />
Cholesterol<br />
ABCA1<br />
+ LXRα<br />
ApoE<br />
+ LXRα<br />
ApoA-I<br />
22(R)-HC<br />
9-cis-RA<br />
RXRα LXRα<br />
27-Hydroxycholesterol<br />
LpE<br />
Plasma<br />
membrane<br />
RXRα<br />
Nucleus<br />
LXRα<br />
ABCA1 gene<br />
Regulation of body cholesterol<br />
homeostasis by oxysterols and retinoids<br />
oxysterols<br />
(via LXR)<br />
retinoids<br />
(via RXR)<br />
ABCG5 & ABCG8<br />
ABCA1 , apoE<br />
ABCA1<br />
ABCG5 & ABCG8<br />
CYP7A<br />
BSEP<br />
ABCA1<br />
cholesterol resorption<br />
cholesterol efflux<br />
HDL formation<br />
biliary chol. secretion<br />
bile acid synthesis<br />
Bile acids<br />
(via FXR)<br />
bile acid secretion<br />
cholesterol backflux<br />
liver<br />
blood<br />
brain<br />
barrier<br />
Regulation of cholesterol transport by<br />
ABC lipid transporters<br />
oxLDL<br />
cholesterol<br />
bile acid<br />
LXRα<br />
ABCA1<br />
BLOOD<br />
HDL<br />
ABCG5<br />
ABCG8<br />
CYP7A<br />
LXRα<br />
ABCA1? ABCB11<br />
LXRα<br />
BILE and<br />
INTESTINE<br />
LXRα<br />
FXRα<br />
ABCG5<br />
ABCG8<br />
LXRα<br />
intestine<br />
macrophage<br />
macrophage<br />
hepatocyte<br />
LXRα<br />
enterocyte<br />
ABCA1?<br />
CHY-<br />
LUS<br />
ABCC3?<br />
FXRα<br />
Cholesterol<br />
Transport<br />
Pool<br />
Cholesterol<br />
Transport<br />
Pool<br />
LXRα<br />
SREBP1<br />
FAS,<br />
FAT<br />
dietary<br />
cholesterol<br />
LXRα<br />
ABCG5<br />
ABCG8<br />
FXR<br />
BSEP<br />
LXRα<br />
CYP7A<br />
CYP8B<br />
FXR<br />
NTCP<br />
dietary<br />
cholesterol<br />
LXRα<br />
ABCG5<br />
ABCG8<br />
FXR<br />
BSEP<br />
LXRα<br />
CYP7A<br />
CYP8B<br />
FXR<br />
NTCP<br />
HMG-<br />
CoA-<br />
Red.<br />
SREBP2<br />
LDL-R<br />
LDL<br />
VLDL<br />
FXR<br />
I-BABP<br />
CM<br />
CMR<br />
FXR<br />
I-BABP<br />
CM<br />
CMR<br />
LXRα<br />
ABCG5<br />
ABCG8<br />
ABCA1<br />
LXRα<br />
ABCG5<br />
ABCG8<br />
ABCA1
Cholesterol<br />
Transport<br />
dietary<br />
cholesterol<br />
LXRα<br />
ABCG5<br />
ABCG8<br />
FXR<br />
BSEP<br />
Pool<br />
LXRα<br />
CYP7A<br />
CYP8B<br />
FXR<br />
NTCP<br />
LXRα<br />
SREBP1<br />
FAS,<br />
FAT<br />
HMG-<br />
CoA-<br />
Red.<br />
SREBP2<br />
LDL-R<br />
LDL<br />
VLDL<br />
LXRα<br />
ABCA1<br />
LXRα<br />
CETP<br />
dietary<br />
cholesterol<br />
(0.2 - 0.5 g)<br />
Bile acids<br />
((2 - 3 g) x 10)<br />
Pool<br />
Cholesterol<br />
biosynthesis<br />
(0.5 - 1.0 g)<br />
LDL<br />
VLDL<br />
HDL<br />
HDL<br />
FXR<br />
I-BABP<br />
CM<br />
CMR<br />
CM<br />
CMR<br />
LXRα<br />
ABCG5<br />
ABCG8<br />
ABCA1<br />
LXRα<br />
ABCA1, ApoE<br />
Cholesterol excretion (0.5 g)<br />
Cholesterol synthesis<br />
(0.5 - 1.0 g)
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