ライフサイエンスコーパス: LPL

1 LPL hydrolyzes triacylglycerol, which increases local su

2 LPL polymorphisms and triglycerides were determined and

3 LPL was required for the transition from prealveolar mac

4 LPL(-/-) mice demonstrated a very early clearance defect

5 LPL, GCKR, and APOA5 polymorphisms fit dominant, recessi

6 e-adiposity (APOA5, APOB, APOE, GCKR, IRS-1, LPL, MTHFR, PCSK9, PNPLA3, PPARgamma2), gene-exercise (A

7 tutions in GPIHBP1's Ly6 domain that abolish LPL binding lead to protein dimerization/multimerization

8 09 with any of 8 other amino acids abolished LPL binding-and often did so without promoting the forma

9 2, and SIRT1) and lipogenesis (SREBP1c, ACC, LPL, and FASN).

10 increase the amount of enzymatically active LPL by preventing its inhibition by angiopoietin-like pr

11 Adipoq-LPL mice also have increased energy expenditure.

12 These mice (Adipoq-LPL) have improved glucose and insulin tolerance as well

13 higher in the epididymal fat pads of Adipoq-LPL mice than control mice.

14 ept for one important difference, the Adipoq-LPL mice did not gain more fat mass on HFD than control

15 ) involved, we determined whether the Adipoq-LPL mice diverted dietary lipid to adipose tissue to red

16 as adiponectin in the adipose of the Adipoq-LPL mice, suggesting that increasing adipose tissue LPL

17 eased adiponectin serum levels in the Adipoq-LPL mice.

18 duces diet-induced obesity without affecting LPL activity.

19 Although LPL and the N-terminal domain formed a tight but short l

20 ace by using chimeric variants of LPL and an LPL peptide mimetic.

21 L structure and activity, we crystallized an LPL-GPIHBP1 complex and solved its structure.

22 oal of contributing to the development of an LPL enzyme replacement therapy.

23 Here, we show that binding of an LPL-specific monoclonal antibody (5D2) to the tryptophan

24 ross capillary endothelial cells and anchors LPL to the capillary wall during lipolysis.

25 Because both ABCG1 and LPL are expressed in adipose tissue, we hypothesized tha

26 Comparison of the APOC3 and LPL associations revealed that APOC3 association results

27 ding intravascular lipolysis and GPIHBP1 and LPL mutations causing familial chylomicronemia.

28 the concomitant increases in lipogenesis and LPL activity.

29 Moreover, PBL and LPL from most patients with active IBD failed to respond

30 ond to F. prausnitzii in contrast to PBL and LPL from patients in remission and/or healthy donors.

31 Rgamma co-occupancy observed on PGC1beta and LPL gene regulatory regions identified.

32 maH2A.X expression in colonic epithelium and LPLs confirmed the contribution of DNA damage response i

33 significantly in both colonic epithelium and LPLs.

34 pattern of immune dysregulation in IELs and LPLs, which featured the expansion of activated lymphocy

35 , whereas minor alleles of ADIPOR2, ANGPTL3, LPL, and TRIB1 polymorphisms were inversely associated.

36 3, PPARgamma2), gene-exercise (APOA1, APOA2, LPL), gene-diet (APOA5, APOE, INSIG2, LPL, MYB, NXPH1, P

37 eatment targets (PCSK9, LDLR, NPC1L1, APOC3, LPL) were not.

38 gene-insulin resistance interactions (APOE, LPL).

39 ote, 5D2-bound LPL monomers are as stable as LPL homodimers (i.e., they are not more prone to unfoldi

40 ep interactions for known lipid loci such as LPL and PCSK9.

41 is for LPL-mediated TRL lipolysis as well as LPL stabilization and transport by GPIHBP1.

42 Intriguingly, astrocytic LPL deficiency also triggered increased ceramide content

43 Likewise, astrocytic LPL deletion reduced the accumulation of lipid droplets

44 ons for lipid levels change were detected at LPL, TRIB1, APOA1-C3-A4-A5, LIPC, CETP, and LDLR (P rang

45 C1-linked heparan sulfate chains and between LPL and the Golgi membrane.

46 fast on- and off-rates, the complex between LPL and the Ly6 domain formed more slowly and persisted

47 f LPL requires bivalent interactions between LPL and SDC1-linked heparan sulfate chains and between L

48 et al. now present a fusion protein between LPL and its physiological transporter GBIHBP1 that is hi

49 to identify potential binding sites between LPL and ANGPTL4.

50 ignificant differences were detected between LPLs isolated from the ethanol and control groups at res

51 udies showed that only GPIHBP1 monomers bind LPL.

52 GPIHBP1-W109S lacked the ability to bind LPL but had a reduced propensity for forming dimers or m

53 The ability of GPIHBP1 to bind LPL depends on the Ly6 domain, a three-fingered structur

54 109 might play a more direct role in binding LPL.

55 only GPIHBP1 monomers are capable of binding LPL.

56 t dimers or multimers-are capable of binding LPL.

57 We found that ANGPTL4 binds LPL near the active site at the lid domain and a nearby

58 ding of GPIHBP1 to LPL alone or to 5D2-bound LPL counteracts ANGPTL4-mediated unfolding of LPL.

59 Of note, 5D2-bound LPL monomers are as stable as LPL homodimers (i.e., they

60 sequence, confer targeting of SDC1 and bound LPL into the sphingomyelin secretion pathway.

61 GPIHBP1-bound LPL is essential for the margination of triglyceride-ric

62 in inactivating both free and GPIHBP1-bound LPL.

63 The Q114P mutant bound LPL similarly to the N-terminal domain of GPIHBP1.

64 Hydrolysis of plasma triglycerides by LPL can be disrupted by the protein angiopoietin-like 4

65 d three novel signals associated with HDL-C (LPL, APOA5, LCAT) and two associated with LDL-C (ABCG8,

66 eficiency had increased postprandial cardiac LPL activity and lower TAG levels only in the fed state.

67 A), gene-alcohol (ALDH2, APOA5, APOC3, CETP, LPL), gene-smoking (APOC3, CYBA, LPL, USF1), gene-pregna

68 2/DOCK6 and NCAN/MAU2 for total cholesterol, LPL, ABCA1, ZNF259/APOA5, LIPC and CETP for HDL choleste

69 By coexpressing LPL with a soluble variant of its accessory protein glyc

70 the frequencies of DP8alpha PBL and colonic LPL were lower in patients with IBD than in healthy dono

71 roup but less evident in jejunal and colonic LPLs compared with controls, suggesting a more significa

72 n the metabolic measures and used the common LPL(rs12678919) polymorphism to test for LPL-independent

73 rference in 3T3-L1 preadipocytes compromised LPL-dependent TG accumulation during the initial phase o

74 Severely compromised LPL activity causes familial chylomicronemia syndrome (F

75 t these ANGPTLs inactivate LPL by converting LPL homodimers into monomers, rendering them highly susc

76 POC3, CETP, LPL), gene-smoking (APOC3, CYBA, LPL, USF1), gene-pregnancy (LPL), and gene-insulin resis

77 eron gamma (IFNgamma)-expressing T cytotoxic LPLs and fecal albumin and between inflammatory taxa abu

78 lts in multimerization of GPIHBP1, defective LPL binding, and severe hypertriglyceridemia.

79 nd helices are composed of inactive dihedral LPL dimers.

80 Heparin dissociated LPL from the N-terminal domain, and partially from wild

81 lation were pronounced in ileal and duodenal LPLs from the ethanol-drinking group but less evident in

82 ol myristate acetate and ionomycin, duodenal LPLs from ethanol-drinking animals generated a dampened

83 Deficiencies in either LPL or GPIHBP1 impair triglyceride hydrolysis, resulting

84 olution fluorescent microscopy of endogenous LPL revealed that LPL adopts a filament-like distributio

85 ike protein 4 (ANGPTL4), a potent endogenous LPL inhibitor, was significantly increased during pregna

86 AT, likely via activation of AMPK, enhancing LPL activity and uptake of plasma triglyceride-derived f

87 wn-regulation of the mRNA level of aP2, FAS, LPL, HSL and PLIN1.

88 ructures illuminate the structural basis for LPL-mediated TRL lipolysis as well as LPL stabilization

89 l-rich lipoproteins and is the co-factor for LPL as pressure increases.

90 il very recently, structural information for LPL was limited to homology models, presumably due to th

91 ges to long-standing dogma on mechanisms for LPL inactivation by ANGPTL proteins.

92 idemia (chylomicronemia), but structures for LPL and GPIHBP1 have remained elusive.

93 mon LPL(rs12678919) polymorphism to test for LPL-independent effects.

94 LPL prevents homodimer formation and forces LPL into a monomeric state.

95 Furthermore, LPL that was bound to the N-terminal domain interacted w

96 work conceptualizes a model for the GPIHBP1*LPL interaction based on biophysical measurements with h

97 ravascular processing of TRLs by the GPIHBP1-LPL complex is crucial for the generation of lipid nutri

98 resent a cryo-EM reconstruction of a helical LPL oligomer at 3.8- angstrom resolution.

99 Mutation of one of the helical LPL interaction interfaces causes loss of the filament-l

100 (LMF1), we obtained a stable and homogenous LPL/GPIHBP1 complex that was suitable for structure dete

101 eport here X-ray crystal structures of human LPL in complex with human GPIHBP1 at 2.5-3.0 angstrom re

102 We conclude that hypothalamic LPL functions in astrocytes to ensure appropriately bala

103 These results identify LPL as a key effector of Mst1 and establish a novel mech

104 of the fusion protein enabled us to identify LPL amino acids that interact with ANGPTL4.

105 dampened response, whereas jejunal and ileal LPLs from ethanol-drinking animals produced a heightened

106 Common genetic variants found in LPL, APOA5, and GCKR are associated with triglycerides l

107 n WAT, abolishing a cold-induced increase in LPL activity.

108 Furthermore, expression of T89A LPL in LPL-deficient hematopoietic cells, using bone marrow chi

109 ulated in developing alveolar macrophages in LPL(-/-) pups, suggesting that precursor cells were not

110 pase; we therefore searched for mutations in LPL and identified a loss-of-function variant that was a

111 Mutations in LPL cause a rare but debilitating disorder characterized

112 Loss-of-function mutations in LPL or GPIHBP1 cause severe hypertriglyceridemia (chylom

113 index, glucose, sex, rs328 and rs7007797 in LPL, rs662799 and rs3135506 in APOA5, and rs1260326 in G

114 ylated p65(+) cells was markedly elevated in LPLs of chronically SIV-infected macaques compared with

115 de that ANGPTL4 can both bind and inactivate LPL complexed to GPIHBP1 and that inactivation of LPL by

116 Dogma has held that these ANGPTLs inactivate LPL by converting LPL homodimers into monomers, renderin

117 4), and ANGPTL4 has been shown to inactivate LPL in vitro.

118 We also show that ANGPTL4-inactivated LPL was incapable of binding GPIHBP1.

119 Once inactivated, LPL dissociated from GPIHBP1.

120 We now show: (1) that ANGPTL4 inactivates LPL by catalyzing the unfolding of its hydrolase domain;

121 PTL4 was capable of binding and inactivating LPL complexed to GPIHBP1 on the surface of endothelial c

122 as capable of binding, but not inactivating, LPL at 4 degrees C, suggesting that binding alone was no

123 o, the existence of a condensed and inactive LPL oligomer was proposed.

124 upplementation are associated with increased LPL activity, whereas the null effect of EPA supplementa

125 n of the fragmentation pattern of individual LPL class and optimization of all experimental condition

126 is unlikely that apoC-I and apoC-III inhibit LPL via displacement of apoC-II from the lipoprotein sur

127 s suggest that ANGPTL4 specifically inhibits LPL by binding the lid domain, which could prevent subst

128 the lipasin-Angptl3 pathway, which inhibits LPL in cardiac and skeletal muscles to direct circulatin

129 ely, fasting induces Angptl4, which inhibits LPL in WAT to direct circulating TAG to cardiac and skel

130 APOA2, LPL), gene-diet (APOA5, APOE, INSIG2, LPL, MYB, NXPH1, PER2, TNFA), gene-alcohol (ALDH2, APOA5

131 The altered intestinal LPL function detected in our study reveals remarkable re

132 Small intestinal LPLs had increased numbers of CD44(hi), CD62L(lo), KLRG1

133 , our findings align well with insights into LPL function from the recent crystal structure of the LP

134 ole of APOC3 in triglyceride metabolism, its LPL independent action, and the complex and correlated n

135 nary, cerebral, peripheral), including LDLR, LPL and LPA, suggesting that therapeutic modulation of l

136 oth epithelial and lamina propria leukocyte (LPL) compartments.

137 onal responses of lamina propria leukocytes (LPLs) isolated from the 4 major gut sections.

138 h the APOA5, APOC1, BRAP, BUD13, CETP, LIPA, LPL, PLCG1, and ZPR1 genes.

139 4 inhibits extracellular lipoprotein lipase (LPL) activity and stimulates the lipolysis of triacylgly

140 kers of lipogenesis, and lipoprotein lipase (LPL) activity in adults participating in a double-blind,

141 ppHF dams, but systemic lipoprotein lipase (LPL) activity was increased, suggesting that increased b

142 a protein that inhibits lipoprotein lipase (LPL) activity, is highly expressed in BAT.

143 We also detect lipoprotein lipase (LPL) and apolipoprotein A5 (APOA5) harbouring specific A

144 to remnant particles by lipoprotein lipase (LPL) and their uptake by the liver.

145 II) is the co-factor for lipoprotein lipase (LPL) at the surface of triacylglycerol-rich lipoproteins

146 uring the soluble enzyme lipoprotein lipase (LPL) during export from the TGN.

147 protein that transports lipoprotein lipase (LPL) from the subendothelial space to the luminal side o

148 translated region of the lipoprotein lipase (LPL) gene.

149 Lipoprotein lipase (LPL) hydrolyzes fatty acids (FAs) from triglyceride (TAG

150 ter drives expression of lipoprotein lipase (LPL) in adipocytes to potentially increase adipose tissu

151 whether lipid uptake via lipoprotein lipase (LPL) in astrocytes is required to centrally regulate ene

152 Lipoprotein lipase (LPL) is active in capillaries, where it plays a crucial

153 Lipoprotein lipase (LPL) is an enzyme responsible for clearing triglycerides

154 Lipoprotein lipase (LPL) is central to triglyceride metabolism.

155 The enzyme lipoprotein lipase (LPL) is responsible for breaking down triglycerides in t

156 Lipoprotein lipase (LPL) is responsible for the intravascular processing of

157 We show that lipoprotein lipase (LPL) may more efficiently hydrolyze medium length triacy

158 Lipoprotein lipase (LPL) plays a central role in triglyceride (TG) metabolis

159 The binding of lipoprotein lipase (LPL) to GPIHBP1 focuses the intravascular hydrolysis of

160 Lipoprotein lipase (LPL) undergoes spontaneous inactivation via global unfol

161 A in situ hybridization, lipoprotein lipase (LPL) was found to be expressed in endothelial cells of c

162 or 1beta (PGC1beta), and lipoprotein lipase (LPL) were among the up-regulated genes identified.

163 thelial cells that binds lipoprotein lipase (LPL) within the interstitial space and shuttles it to th

164 endothelial cells, binds lipoprotein lipase (LPL) within the subendothelial spaces and shuttles it to

165 d-binding protein (aP2), lipoprotein lipase (LPL), fatty acid synthase (FAS), hormone sensitive lipas

166 asma TGs in mice lacking lipoprotein lipase (LPL), hepatic heparan sulfate proteoglycan (HSPG) recept

167 ion, and relation to the lipoprotein lipase (LPL), however, remain elusive.

168 ion of the gene encoding lipoprotein lipase (LPL), which was upregulated in zebrafish melanocyte tumo

169 f the bioavailability of lipoprotein lipase (LPL).

170 dependent on the enzyme lipoprotein lipase (LPL).

171 s due to a deficiency in lipoprotein lipase (LPL).

172 ng alleles involved in peripheral lipolysis (LPL and ANGPTL4) had no effect on liver fat but decrease

173 Triglyceride-lowering LPL variants and LDL-C-lowering LDLR variants were assoc

174 Eight loci (PCSK9, LPA, LPL, LIPG, ANGPTL4, APOB, APOC3, and CD300LG) remained s

175 phocyte (IEL) and lamina propria lymphocyte (LPL) activation status and cytokine production (flow cyt

176 Using colonic lamina propria lymphocytes (LPL) and peripheral blood lymphocytes (PBL) from healthy

177 In lamina propria lymphocytes (LPLs), STAT4 activation by LIF blocks STAT3-dependent Il

178 were elevated in lamina propria lymphocytes (LPLs).

179 comprehensive analysis of lysophospholipid (LPL) species based on shotgun lipidomics has not been es

180 hat separating the FLD from the CCD-mediated LPL-inhibitory activity of full-length Angptl4 reveals l

181 work, we further characterized the monomeric LPL/GPIHBP1 complex and its derivative, the LPL-GPIHBP1

182 ike in energy-dependent cells like myocytes, LPL is normally repressed in adult hepatocytes.

183 vo studies showed that postnatal ablation of LPL in glial fibrillary acidic protein-expressing astroc

184 e study revealed significant accumulation of LPL species in the liver of ob/ob mice.

185 ase surface pressure and mimic the action of LPL.

186 ggest that apoC-II regulates the activity of LPL in a pressure-dependent manner.

187 exhibited elevated postprandial activity of LPL in the heart and skeletal muscle, but not in white a

188 The activity of LPL in tissues is regulated by angiopoietin-like protein

189 ting that lipasin suppresses the activity of LPL specifically in cardiac and skeletal muscles.

190 L by ANGPTL4 greatly reduces the affinity of LPL for GPIHBP1.

191 Mice expressing a conditional allele of LPL (CD11c.Cre(pos)-LPL(fl/fl)) exhibited significant re

192 od was applied for comprehensive analysis of LPL species present in mouse liver samples.

193 r comprehensive and quantitative analysis of LPL species was developed.

194 Depletion or antagonism of LPL suppressed human melanoma cell growth; this required

195 g with that finding, there was no binding of LPL to GPIHBP1-S107C in either cell-based or cell-free b

196 g of LPL, does not require the conversion of LPL homodimers into monomers.

197 The regulatory N-terminal domain of LPL contains a consensus Mst1 phosphorylation site at Th

198 rotein metabolism, as well as the effects of LPL(rs12678919).

199 ision energy, and recovery and enrichment of LPL classes from the aqueous phase after solvent extract

200 is the first study to show the expression of LPL from the vascular endothelium in chickens.

201 y role of the top GWAS SNP for expression of LPL, FADS2 and C6orf184.

202 ctivator PPARGC1B, and reduced expression of LPL.

203 ently with LPL and that the functionality of LPL depends on its localization on GPIHBP1.

204 Fusion of LPL to GPIHBP1 increased yields of recombinant LPL, prev

205 omplexed to GPIHBP1 and that inactivation of LPL by ANGPTL4 greatly reduces the affinity of LPL for G

206 conclusion, ANGPTL4-mediated inactivation of LPL, accomplished by catalyzing the unfolding of LPL, do

207 -like 4 (ANGPTL4) mediates the inhibition of LPL activity under different circumstances.

208 ely resistant to physiological inhibitors of LPL.

209 cal relevance of the inherent instability of LPL, and sheds light on the molecular defects in a clini

210 Unlike the interaction of LPL with the Ly6 domain, the interaction of LPL with the

211 LPL with the Ly6 domain, the interaction of LPL with the N-terminal domain was significantly weakene

212 ifferent roles in regulating the kinetics of LPL binding.

213 All three homozygotes had very low levels of LPL in the preheparin plasma.

214 ting Thr(89) to Ala impaired localization of LPL to the actin-rich lamellipodia of T cells.

215 9A LPL mutant failed to restore migration of LPL-deficient T cells in vitro.

216 models, presumably due to the propensity of LPL to unfold and aggregate.

217 idates the molecular basis for regulation of LPL activity by ANGPTL4, highlights the physiological re

218 port the role of APOC3 as a key regulator of LPL-independent pathways of triglyceride metabolism.

219 This triggers release of LPL from lipoproteins.

220 d metabolism and for elucidating the role of LPL species in signal transduction and other biological

221 Sorting of LPL requires bivalent interactions between LPL and SDC1-

222 ermination of the first crystal structure of LPL that includes these important regions of the protein

223 pid-binding loop in the carboxyl terminus of LPL prevents homodimer formation and forces LPL into a m

224 tivity by mitigating the global unfolding of LPL's catalytic domain.

225 accomplished by catalyzing the unfolding of LPL, does not require the conversion of LPL homodimers i

226 PL counteracts ANGPTL4-mediated unfolding of LPL.

227 ess efficient in catalyzing the unfolding of LPL; and (2) that its Glu-to-Lys substitution destabiliz

228 tein interface by using chimeric variants of LPL and an LPL peptide mimetic.

229 l differences in composition and function of LPLs independent of alcohol consumption.

230 Thr(89) We found that Mst1 can phosphorylate LPL in vitro and that Mst1 can interact with LPL in cell

231 nt for the actin-bundling protein L-plastin (LPL) have phenotypes similar to mice lacking Mst1, inclu

232 w that the actin-bundling protein L-plastin (LPL) is required for the perinatal development of alveol

233 a conditional allele of LPL (CD11c.Cre(pos)-LPL(fl/fl)) exhibited significant reductions in alveolar

234 ng (APOC3, CYBA, LPL, USF1), gene-pregnancy (LPL), and gene-insulin resistance interactions (APOE, LP

235 r the analysis of fatty acids and preheparin LPL activity.

236 with a novel strategy of sample preparation, LPL species present in biological samples can be determi

237 overy that GPIHBP1's acidic domain preserves LPL structure and activity, we crystallized an LPL-GPIHB

238 echanisms by which GPIHBP1 mutations prevent LPL binding and lead to chylomicronemia.

239 creased yields of recombinant LPL, prevented LPL aggregation, stabilized LPL against spontaneous inac

240 glioma capillaries captures locally produced LPL.

241 ymphocytes in the intestinal lamina propria (LPL) and cervical lymph nodes (CLN).

242 gregation, and poor stability of recombinant LPL have thus far prevented development of enzyme replac

243 L to GPIHBP1 increased yields of recombinant LPL, prevented LPL aggregation, stabilized LPL against s

244 domain; (2) that binding to GPIHBP1 renders LPL largely refractory to this inhibition; and (3) that

245 -29a as the miRNA responsible for repressing LPL in hepatocytes, and found that decreasing hepatic mi

246 of alveolar macrophage development requiring LPL.

247 that rs174545 (FADS1:miR-181a-2), rs1059611 (LPL:miR-136), rs13702 (LPL:miR-410), rs1046875 (FN3KRP:m

248 R-181a-2), rs1059611 (LPL:miR-136), rs13702 (LPL:miR-410), rs1046875 (FN3KRP:miR-34a), rs7956 (MKRN2:

249 t LPL, prevented LPL aggregation, stabilized LPL against spontaneous inactivation, and made it resist

250 Heparin binding stabilizes LPL helices, and the presence of substrate triggers heli

251 Importantly, the acidic domain stabilizes LPL catalytic activity by mitigating the global unfoldin

252 ikely explanation for how GPIHBP1 stabilizes LPL.

253 Furthermore, expression of T89A LPL in LPL-deficient hematopoietic cells, using bone mar

254 Expression of the T89A LPL mutant failed to restore migration of LPL-deficient

255 We found that LPL supports 2 actin-based processes essential for corre

256 d here are consistent with a new report that LPL, in complex with GPIHBP1, can be active as a monomer

257 t microscopy of endogenous LPL revealed that LPL adopts a filament-like distribution in vesicles.

258 ysis of electrostatic surfaces revealed that LPL contains a large basic patch spanning its N- and C-t

259 hypothalamus-derived astrocytes showed that LPL expression is upregulated by oleic acid, whereas it

260 Recently, we showed that LPL monomers form 1:1 complexes with the LPL transporter

261 Taken together, this suggests that LPL is condensed into its inactive helical form for stor

262 It was assumed for many years that LPL was only active as a homodimer.

263 The LPL within capillaries is bound to GPIHBP1, an endotheli

264 The LPL*GPIHBP1 complex is responsible for margination of tr

265 The LPL-GPIHBP1 structure provides insights into mutations c

266 Additionally, the LPL-GPIHBP1 fusion protein exhibited high enzyme activit

267 and made it resistant to inactivation by the LPL antagonists angiopoietin-like protein 3 (ANGPTL3) or

268 LPL/GPIHBP1 complex and its derivative, the LPL-GPIHBP1 fusion protein, with the goal of contributin

269 310) subunit of NF-kappaB exclusively in the LPL compartment.

270 sed of triglyceride-lowering variants in the LPL gene and LDL-C-lowering variants in the LDLR gene, r

271 differences in associated lipid levels, the LPL and LDLR scores were associated with similar lower r

272 r level of ApoB-containing lipoproteins, the LPL score was associated with 69.9-mg/dL (95% CI, 68.1-7

273 of the inhibitor resulted in ordering of the LPL lid and lipid-binding regions and thus enabled deter

274 work has shed light on the structure of the LPL monomer, the inactive oligomer remained opaque.

275 ion from the recent crystal structure of the LPL*GPIHBP1 complex.

276 The structural details of the LPL-ANGPTL4 interaction uncovered here may inform the de

277 These results indicate that the LPL-GPIHBP1 fusion protein has potential for use as a th

278 , LDL-C, and ApoB levels associated with the LPL and LDLR genetic scores.

279 hat LPL monomers form 1:1 complexes with the LPL transporter glycosylphosphatidylinositol-anchored hi

280 Therefore, LPL is a good target for triglyceride-lowering therapeut

281 y predictable by the action of APOC3 through LPL.

282 e, suggesting that increasing adipose tissue LPL improves glucose metabolism in diet-induced obesity

283 NGPTL4 both bound with similar affinities to LPL, the N-terminal fragment was more potent in inactiva

284 GPIHBP1's LU domain binds to LPL's C-terminal domain, largely by hydrophobic interact

285 a structure with a novel inhibitor bound to LPL.

286 Binding of GPIHBP1 to LPL alone or to 5D2-bound LPL counteracts ANGPTL4-mediat

287 GPIHBP1 is responsible for trafficking LPL across capillary endothelial cells and anchors LPL t

288 TGs present in TG-rich lipoproteins (TRLs), LPL facilitates TG utilization and regulates circulating

289 However, in vivo LPL is often complexed to glycosylphosphatidylinositol-a

290 When LPL was in complex with the acidic peptide corresponding

291 e from 4.84x10(-4) to 4.62x10(-18)), whereas LPL, TRIB1, ABCA1, APOA1-C3-A4-A5, CETP, and APOE displa

292 domain interacted with lipoproteins, whereas LPL bound to the Ly6 domain did not.

293 We therefore asked whether LPL functions downstream of Mst1.

294 nvestigated the interactions of ANGPTL4 with LPL-GPIHBP1 complexes on the surface of endothelial cell

295 mains of GPIHBP1 interact independently with LPL and that the functionality of LPL depends on its loc

296 in and the central Ly6 domain, interact with LPL as two distinct binding sites.

297 LPL in vitro and that Mst1 can interact with LPL in cells.

298 sity map but was positioned to interact with LPL's large basic patch, providing a likely explanation

299 How ANGPTL4 interacts with LPL in this context is not known.

300 IHBP1 missense mutations that interfere with LPL binding cause familial chylomicronemia.