Lipid Metabolism Prof. Dr. rer physiol. Dr.h.c. Ulrike Beisiegel 1 The screen versions of these slides have full details of copyright and acknowledgements Lipid Metabolism 1 Prof. Dr. rer physiol. Dr.h.c. Ulrike Beisiegel Department of Biochemistry and Molecular Biology II Medical Center Hamburg-Eppendorf Lipids… …. visceral fat 2 …. nutritional lipids …. serum lipids …. lipid accumulation in the arterial wall 0 1.5 3 4.5 9 h Karpe et al., Atherosclerosis 1994 Functions of lipids Energy supply Triglycerides Fatty acids Phospho- and shingolipids as structural membrane components COOH 3 Hormones Regulation of gene expression Lipophilic vitamins Cholesterol COOH
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Lipid MetabolismProf. Dr. rer physiol. Dr.h.c. Ulrike Beisiegel
1The screen versions of these slides have full details of copyright and acknowledgements
Lipid Metabolism
1
Prof. Dr. rer physiol. Dr.h.c. Ulrike BeisiegelDepartment of Biochemistry and Molecular Biology II
Medical Center Hamburg-Eppendorf
Lipids……. visceral fat
2
…. nutritional lipids
…. serum lipids
…. lipid accumulation in the arterial wall
0 1.5 3 4.5 9 h
Karpe et al., Atherosclerosis 1994
Functions of lipids
Energy supply
Triglycerides
Fatty acids
Phospho- and shingolipids as structural membrane components
COOH
3
Hormones
Regulation of gene expression
Lipophilic vitamins
Cholesterol
COOH
Lipid MetabolismProf. Dr. rer physiol. Dr.h.c. Ulrike Beisiegel
2The screen versions of these slides have full details of copyright and acknowledgements
1. Postprandial lipid metabolism
2. Hepatic lipid metabolism
3 Cellular cholesterol homoeostasis
Lipid metabolism
4
3. Cellular cholesterol homoeostasis
4. Reverse cholesterol transport
EnterocytesLipid droplets
+ pancreatic lipase
Lipid absorption in the intestinenutritional lipids in:
5
Lipid emulsion
+ phospholipids
+ bile acids
+ pancreatic lipase with cofactor
Micelles
bile acids→ entero-hepatic cycle
fatty acids
cholesterol
cholesterol and plant sterols NPC1L1
Intestinal sterol uptake
Niemann-Pick C1 Like 1 (NPC1L1) protein is responsible for sterol absorption in the small intestine1
Enterocytes
6
plant sterolsand cholesterol
and
The secretion of sterols into bile is mediated jointly by the two ABC-transportersABCG5 and ABCG82
1) Altmann SW et al., Science 20042) Berge KE et al., Science 2000
ABCG5/G8
Lipid MetabolismProf. Dr. rer physiol. Dr.h.c. Ulrike Beisiegel
3The screen versions of these slides have full details of copyright and acknowledgements
Fatty acids
and cholesterol
CD36
Intestinal fatty acid uptake
Enterocytes
COOH
CD36 is a fatty acid translocase (FAT) with a broad ligand specificityproximal
7
Fatty acidsFATP4
Stahl A et al., Mol Cell 1999; Nassir F et al., JBC 2007
Fatty acid transport protein 4 (FATP4)is a member of the large family of fatty acid transport proteins
ACAT= Acyl-Cholesterin-Acyl-TransferaseSREBP = Sterol regulated element binding protein
Storage ↑ACAT
Free intracellular cholesterol regulates synthesis, storage and uptake of cholesterol via regulating the expression of the genes for HMG CoA reductase, ACAT and LDL-receptor
Goldstein and Brown, Science 1986*Brown and Goldstein, PNAS 1999*Gong Y et al., PNAS 2006
Cholesterol acts via the SREBP*
1. Postprandial lipid metabolism
2. Hepatic lipid metabolism
3. Cellular cholesterol homoeostasis
Lipid metabolism
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3. Cellular cholesterol homoeostasis
4. Reverse cholesterol transport
‘Reverse cholesterol transport‘ by HDL
PeripherySR-B1
HDL2
Apo AI
30
Cholesterol
ABCA1
Von Eckardstein A et al., ATVB 2000
HDL-precursorApo AI
HDL3
Apo AI
Lipid MetabolismProf. Dr. rer physiol. Dr.h.c. Ulrike Beisiegel
11The screen versions of these slides have full details of copyright and acknowledgements
Lipid exchange proteins
HDL-precursor
PeripheryHDL2
SR-B1
LCAT
CE
Cholesterol
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PLTP
VLDL orChylomicrons
HDL3
Von Eckardstein A et al.,ATVB 2000
CETP
▲ Cholesterol
TriglyceridesPhospholipids
PLTP = phospholipid transfer proteinCETP= cholesterol ester transfer protein
Total cholesterol < 200 < 200
LDL- cholesterol < 130 < 130
Fasting Postprandial
In mg/dl; generalized from several international recommendations
Normal levels for plasmalipids
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LDL- cholesterol < 130 < 130
HDL- cholesterol > 40 > 40
Total triglycerides < 150 < 300
... relates to primary prevention and is not differentiated for gender
Dietary lipids
33Nordestgaard et al., JAMA 2007
Lipid MetabolismProf. Dr. rer physiol. Dr.h.c. Ulrike Beisiegel
12The screen versions of these slides have full details of copyright and acknowledgements