Protein : LPL

Name LPL
Description lipoprotein lipase
Owner Public
URN urn:agi-llid:4023
Connectivity 80
Notes LPL encodes lipoprotein lipase, which is expressed in heart, muscle, and adipose tissue. LPL functions as a homodimer, and has the dual functions of triglyceride hydrolase and ligand/bridging factor for receptor-mediated lipoprotein uptake. Severe mutations that cause LPL deficiency result in type I hyperlipoproteinemia, while less extreme mutations in LPL are linked to many disorders of lipoprotein metabolism. , quantitative-transmission/disequilibrium-test analyses showed that there was linkage between DBP and two single nucleotide polymorphisms in the LPL gene. APOC3, LPL and GpIIIa genes were found to be associated with BP levels. The contributions of these genes, although modest, are consistent with the polygenic nature of blood pressure levels. Activity may explain the difference in LDL lipoprotein size in diabetic and nondiabetic people. Beta-cell LPL has two physiologically relevant effects in islets, the inverse regulation of glucose metabolism and the independent mediation of insulin secretion through effects distal to membrane depolarization. Data show that human lipoprotein lipase significantly inhibited spontaneous human natural killer cells, but not lymphokine-activated killer cytotoxic activity against bovine pulmonary endothelial cells. Early recognition of severe hypertriglyceridemia in pregnancy may be caused by heterozygosity of this enzyme. H+ allele of the lipoprotein lipase gene HindIII polymorphism is associated with higher plasma triglyceride and lower HDL-cholesterol levels in Chinese patients with early-onset diabetes. In Japanese, poorly controlled type 2 diabetic men had more unfavorable lipid profile than did women counterparts, which may be associated with decreased plasma LPL levels. In Polish LPL-H (G) allele carriers, obesity correlated with free fatty acid tolerance in males, and insulin resistance in females. In the ET state, only the gender difference in mLPL mRNA persisted. FAT/CD36 protein in muscle was higher in women than in men, irrespective of training status. Increased LPL activity improves insulin resistance and reduces adipose accumulation in transgenic rabbits. Increased expression after weight loss may contribute to lower plasma ldl cholesterol and triglycerides in obese premenopausal women. LPL 44X alleles were associated with moderately increased LDL peak particle size. LPL could play a key role in the differentiation of Neuro-2A cells and in the pathophysiological effects of oxidative stress in several neurodegenerative disorders. LPL enzyme activities in 28 healthy subjects with well-controlled Type 1 diabetes, and their relationship with Lp(A-I) and Lp(A-I,A-II). LPL enzyme deficiency causes elevated plasma triglyceride level and subsequent insulin resistance; increased free fatty acids combined with insulin resistance promote gluconeogenesis and hyperglycemia, a vicious circle leading to type 2 diabetes. LPL gene and associated regions might contribute to individual blood pressure variation and hypertension in the Chinese population. LPL has a role in atherosclerosis, chylomicronaemia, obesity, Alzheimer's disease, and dyslipidaemia associated with diabetes, insulin resistance, and infection [review]. LPL is bound to postprandial triglyceride-rich lipoproteins and mediates their hepatic clearance in vivo. LPL lipolysis of emulsion triolein was retarded in chylomicron-free human plasma compared with the hydrolysis activated by isolated apolipoprotein C-II. LPL may represent a link between low adiponectin levels and dyslipidemia in both nondiabetic individuals and patients with type 2 diabetes. LPL-mediated fatty acid uptake is an inefficient process, but may be more efficient in muscle than in adipose tissue. Lipoprotein lipase gene polymorphisms might be involved in predisposition to coronary artery disease. Low mass in preheparin serum of type 2 diabetes mellitus patients and its recovery with insulin therapy. Macrophage LPL activity correlated with body mass index and fat mass. Incubation of patient macrophages with IGF-I for 24 h or differentiation of monocytes from GH-deficient patients into macrophages in presence of this growth factor decreased LPL. Maturation of lipoprotein lipase in the endoplasmic reticulum. Muscle can synthesize tethered, dimeric LpL, but efficient production of this enzyme leading to secretion, and physiological function appears to favor secretion of a noncovalent dimer composed of monomeric subunits. Peroxisome proliferator-activated receptor (PPARalpha and PPARgamma) agonists decrease lipoprotein lipase secretion and glycated LDL uptake by human macrophages. SNP analysis did not provide substantial evidence of an association between polymorphisms in the LPL gene and hypertension status and/or blood pressure levels in Chinese. Single Nucleotide Polymorphisms in Lipoprotein Lipase gene is associated with variation in plasma triglyceride levels Coronary Arteriosclerosis. Spontaneously occurring dissociation of LPL dimer into monomers is accelerated in exon 5 mutants, resulting in conformational changes which result in loss of LPL catalytic activity. TRL-bound LPL activity increases in the postprandial state and is strongly reduced in type 2 diabetes, contributing to postprandial hypertriglyceridemia. The Expression of LPL mRNA as well as protein was highly restricted to leukemic B cells. The LPL D9N genotype was a significant predictor of both baseline carotid plaque area and progression. Heterozygotes for the N9 allele had higher values than did LPL D9/D9 homozygotes. D9N genotype may be a determinant of atherosclerosis. The S447X mutation is associated with anti-atherogenic effects on TG and HDL cholesterol in both genders, and with a moderate protective effect on risk of ischemic heart disease in men. The lipoprotein lipase allele significantly increases the risk of developing Alzheimer's disease , and the risk is mostly associated with the H+H+ genotype. The polymorphisms of intron 8 in lipoprotein lipase influence the blood-lipid metabolism, induce blood vessel rebuilding and play an important role in the invasion and development of Essential Hypertension. These results by showing modulation of association between S447X variant of the LPL gene and serum TG by C-514T variant of the HL gene underscore the importance of gene-gene interactions in the assessment of genetic effects on complex traits. Variants in gene relate to presence and degree of microalbuminuria in Type II diabetes. Variation in the LPL gene plays a role in determining insulin resistance in Mexican Americans. W86R mutation was the reason for the production of nonfunctional LPL and consequently triacylglycerol (TG) exceeding 15 mmol/l. X447 allele at the LPL locus is common and associated with a less atherogenic lipid profile in Asian populations. Both hyperglycemia and hyperinsulinemia plus hyperglycemia reduced LPL activity to 60 %. Conclude that type IIB VLDL-1 and VLDL-2 induce triglyceride accumulation in monocyte-macrophages primarily by the lipolytic action of LPL, which may involve stabilization and activation of the enzyme, rather than modulation of enzyme production. Data indicate an important role of endoplasmic reticulum-based chaperones for the folding/dimerization of lipoprotein lipase. Did not find significant effects of lipoprotein lipase HindIII or PvuII polymorphisms on the fasting lipids but HindIII variation was associated with higher triglyceride postprandial peak. Findings of variation near the LPL gene support the proposition that a region near the lipoprotein lipase gene or the lipoprotein lipase gene itself might contribute to the individual blood pressure variation in Chinese. High concentration of triglyceride and/or low concentration of HDL-cholesterol are associated with high blood pressure in hypertensive patients with the X447 allele of the LPL gene. Lipoprotein lipase cannot be a major factor in pathogenesis of Alzheimer's disease. Lipoprotein lipase has a protective role against coronary artery disease in Mexican-Americans. Macrophage-derived LPL in the arterial wall is pro-atherogenic, possibly via the enhancement of foam cell formation during atherogenesis. Mean LDL particle diameter was smaller in LPL N9 carriers; the LPL N9 and S291 alleles are more frequent in CHD-free men with normal HDL-C, whereas the X447 allele is less frequent; the N9 allele is associated with the LDL subclass response to gemfibrozil. Molecular modeling of its dimeric structure. Quantification of LPL and ADAM29 gene expression is a strong prognostic indicator in CLL, providing better prognostic assessment than ZAP-70 in advanced stages of the disease. Results demonstrate a direct effect of prolactin, via functional prolactin receptors, in reducing the lipoprotein lipase activity in human adipose tissue. Results imply that systemic elevation of lipoprotein lipase expression may be potentially useful for the treatment of hyperlipidemias, obesity, and insulin resistance. Results suggest that the nature of the mutation in the LPL gene modifies the relationship of HDL particle size to other metabolic variables and secondary factors such as abdominal obesity and gender. Role of Sp1 and Sp3 in interferon-gamma mediated suppression of gene transcription. Some single-nucleotide polymorphisms in the LPL gene among Chinese associated with abnormal lipid and lipoprotein profiles and predisposition to coronary heart disease, and they are gender-specific. The LPL association with lipid profile is more likely attributable to the functional S447X rather than the nonfunctional exon 10 SNP. The lipoprotein lipase X447 mutant allele may have a role in preventing myocardial infarct risk. Variation in the 3' untranslated region of LPL affects LPL expression and activity, consequently influencing risk of atherosclerosis and insulin resistance. Variations in genes affecting the removal rate of triglycerides (TG) from plasma significantly influence the lipid phenotypic expression of familial combined hyperlipidemia.
Hugo ID 6677

Microarray ID 1386965_at
l03294_at
l03294_g_at
rc_ai237731_s_at
A_43_P11479
A_51_P259296
A_52_P257812
203548_s_at
41209_at
203549_s_at
M15856_at
A_23_P146233
A_14_P139515
R184
OR0343
N097
OH1710A
MB527

GenBank ID AK153428
AK154419
AK155917
AK159268
AK170106
AK170486
BAB22256
BAC32204
BAC37646
BAC39594
BAE29470
BAE29491
BAE29507
BAE29577
BAE29604
BAE29618
BAE29639
BAE29672
BAE29679
BAE29686
BAE29733
BAE29754
BAE29770
BAE30011
BAE30015
BAE30029
BAE30055
BAE30066
BAE30105
BAE30110
BAE30115
BAE30192
BAE30343
BAE30397
BAE30470
BAE30486
BAE30505
BAE30564
BAE30604
BAE30622
BAE30645
BAE30678
BAE30680
BAE30701
BAE30723
BAE30754
BAE30758
BAE30760
BAE30777
BAE30876
BAE30894
BAE30905
BAE30909
BAE30930
BAE31144
BAE31178
BAE31188
BAE31394
BAE31454
BAE31487
BAE31557
BAE31646
BAE31758
BAE31834
BAE31984
BAE31986
BAE34947
BAE41828
BC003305
CAJ18552
CT010344
J03302
M60838
M60839
M60840
M60841
M60842
M60843
M60844
M60845
M60846
M60847
M63335
M65258
NC_000074
NM_008509
NP_032535
NT_039462
P11152
AAA59528
AAB20999
AAB21000
AAB59536
AAC61679
AAH11353
AAM23256
AAP35372
AAY85371
AF050163
AK092286
AK222464
AY092405
BAD96184
BC011353
BT006726
CAA32564
CAA38372
CAA48230
CAG33335
CR457054
DQ083390
M15856
M76722
NC_000008
NM_000237
NP_000228
NT_030737
NT_086740
P06858
S76076
S76077
X14390
X54516
X68111
AAB91541
AAH03738
AK010920
AK011379
AK077829
AK079525
BAB27579
BAC37025
BAC37671
BC003738
BC022586
BC040809
NC_000072
NM_009013
NP_033039
NT_039356
U93583
AAA41534
AAH81836
BC081836
L03294
NC_005115
NM_012598
NP_036730
NW_047470
Q06000
AA726364
AAA39440
AAA39441
AAA39442
AAC04464
AAH03305
AK002645
AK017272
AK045064
AK079446
AK080872
AK086023
AK089473
AK089543
AK150328
AK150355
AK150375
AK150457
AK150488
AK150505
AK150532
AK150577
AK150585
AK150593
AK150646
AK150672
AK150691
AK150984
AK150990
AK151006
AK151038
AK151049
AK151093
AK151099
AK151105
AK151112
AK151195
AK151216
AK151369
AK151434
AK151521
AK151540
AK151563
AK151630
AK151679
AK151698
AK151727
AK151772
AK151774
AK151801
AK151828
AK151866
AK151870
AK151872
AK151893
AK151925
AK152014
AK152035
AK152049
AK152053
AK152079
AK152238
AK152251
AK152350
AK152390
AK152400
AK152481
AK152657
AK152706
AK152733
AK152775
AK152869
51466871
4557726
4557727
51467159
3293304
3293305
21309828
21309829
187215
553523
242989
242990
34389
4379028
21750843
15030192
15030193
30582290
30582291
48146224
48146225
187209
307138
34404
34405
34382
34383
126314
AH001996
51764183
6678709
6678710
198851
198862
198852
198853
198854
198855
198856
198857
198858
198859
198860
198830
2911254
2744071
12832782
12832783
12856426
26337040
26337041
26347994
34877892
6981167
6981168
51858618
51858619
205214
205215
462538
26347995
26351914
26351915
26105346
13097035
13097036
198849
387406
198863
198864
417255
242987
242988
AK152956
AK153006
AK153148
AK153242
AK153425

Chromosome position 8p22
8 33.0 cM
16p14
6 61.3 cM

GO ID 0003824
0004465
0005319
0006631
0008015
0008201
0016020
0016042
0016787
0042627
0003677
0003723
0005554
0005634
0006281
0006310
0006974
0005576
0005615
0006629

Alias Lpl
RAD51 associated protein 1
Rad51ap1
2510006L10Rik
RIKEN cDNA 2510006L10 gene
postheparin esterase
2',3'-exoribonuclease
3'-exoribonuclease
clearing factor lipase
diacylglycerol hydrolase
diglyceride lipase
lipemia-clearing factor
RAD51 associated protein I
Lipoprotein lipase precursor
LIPD
postheparin lipase
O 1-4 V
2',3'-exoribonucleases
3'-exoribonucleases
clearing factor lipases
diacylglycerol hydrolases
diacylglycerol lipases
postheparin esterases
PIR51
O 1-4 Vs
O 1-4-5s
mgc93586
lipemia-clearing factors
postheparin lipases
RAD51-interactive protein
O 1-4-5
Rad51ap I
diacylglycerol lipase
diglyceride lipases
RAD51-interacting protein

Organism Rattus norvegicus
Homo sapiens
Mus musculus

MedLine Reference 12466851
1969408
9192668

LocusLink ID 16956
4023
112420
19362
24539

FunctionalClass catalytic
heparin binding
hydrolase
lipid transporter
lipoprotein lipase
DNA binding
RNA binding
molecular function unknown

RGD ID 3017

Hugo Symbol LPL

Unigene ID Rn.3834
Hs.180878
Mm.1514

KEGG pathway Alzheimer's disease
Glycerolipid metabolism

GO Cellular Component nucleus
extracellular region
chylomicron
membrane
extracellular space

Cell Localization Plasma membrane

Pathway AGT-LRP2
F2-LRP2
IFNG-HLA-C
IFNG-IFNGR1
IFNG-IFNGR2
IGF1-BST1
IGF1-IGF2R
IGF1-LRP5
IL6-LIFR
INS-HLA-DRB1
INS-TFRC
LEP-LRP2
LPA-LDLR
LPA-LRP2
MDK-LRP2
PLG-LRP2
SCGB1A1-LRP2
TG-LDLR
TG-LRP2
THBS1-VLDLR
PPAR all
PPARgamma
PPARalpha
LXR
RXR
NR common targets
PPARalpha large

GO Biological Process DNA recombination
DNA repair
response to DNA damage stimulus
circulation
fatty acid metabolism
lipid catabolism
lipid metabolism

Group Metabolic enzymes

EC Number 3.1.1.34

MGI ID 96820

Swiss-Prot Accession P06858

OMIM ID 238600

Source Curated