Affinage

MTTP

Microsomal triglyceride transfer protein large subunit · UniProt P55157

Length
894 aa
Mass
99.4 kDa
Annotated
2026-06-10
100 papers in source corpus 26 papers cited in narrative 26 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MTTP (microsomal triglyceride transfer protein) is an endoplasmic reticulum lipid-transfer protein that is essential and rate-limiting for the assembly and secretion of apolipoprotein B-containing lipoproteins, including hepatic VLDL and intestinal chylomicrons (PMID:9784135, PMID:10553017, PMID:16354657). It carries two functionally separable activities: an apoB-binding (chaperone) domain that physically engages nascent apoB, and an independent lipid-transfer catalytic domain, since a selective inhibitor of apoB-MTP binding blocks apoB secretion without affecting lipid transfer (PMID:10769147), and abetalipoproteinemia-causing mutations (Y528H, R540C) abolish lipid-transfer activity while retaining normal binding to PDI and apoB (PMID:25108285). MTP binds phospholipid vesicles to form stable ER-luminal MTP-lipid complexes, with zwitterionic phospholipids increasing apoB100 affinity 2-4 fold and negatively charged lipids reducing it (PMID:11427523), and it forms a ternary complex with the TG-binding protein PRAP1 that is required for efficient apoB-lipoprotein assembly (PMID:33168624). Tissue-specific loss-of-function studies establish a cell-autonomous requirement: intestinal deletion abolishes chylomicron assembly and causes enterocyte lipid accumulation (PMID:16354657), and patient-derived MTTP-mutant hepatocytes and cardiomyocytes fail to secrete apoB and accumulate lipid, phenotypes rescued by CRISPR correction (PMID:28514664). Beyond bulk neutral-lipid transfer, an alternately promoted splice variant (MTPv1) transfers phosphatidylethanolamine to CD1d and is required for NKT cell development (PMID:17312007). MTP expression is tightly controlled transcriptionally by HNF4α/HNF1α activation opposed by NR2F1/NCoR1 repression (PMID:22357705), by CLOCK→SHP circadian repression (PMID:20674862), and by insulin-sensitive FoxO6 activation (PMID:24437489), and post-transcriptionally by IRE1β-mediated mRNA degradation in enterocytes (PMID:18460335) and the IRE1α-XBP1s-PDI axis in hepatocytes (PMID:23040069). Loss of MTTP-dependent lipid export drives intracellular lipid retention whose subcellular compartmentalization, rather than steatosis per se, dictates hepatic insulin sensitivity (PMID:32907986).

Mechanistic history

Synthesis pass · year-by-year structured walk · 23 steps
  1. 1998 High

    Established that MTP is required for production of apoB-containing lipoproteins, validating it as the assembly machinery and a pharmacological lipid-lowering target.

    Evidence Small-molecule MTP inhibitors in rodents and WHHL rabbits, with in vitro MTP assay

    PMID:9784135

    Open questions at the time
    • Did not resolve which MTP activity (lipid transfer vs apoB binding) the inhibitors blocked
    • Did not establish whether MTP is rate-limiting under basal conditions
  2. 1999 High

    Showed MTP is rate-limiting for VLDL apoB secretion, not merely permissive, by demonstrating that raising MTP increases lipoprotein output.

    Evidence Adenoviral hepatic MTP overexpression in mice with in vivo secretion-rate measurement

    PMID:10553017

    Open questions at the time
    • Did not address intestinal/chylomicron pathway
    • Mechanism of rate limitation at the molecular step not dissected
  3. 2000 High

    Resolved MTP into two functionally independent domains by showing apoB binding can be inhibited separately from lipid transfer.

    Evidence Competitive binding, co-IP, and a selective apoB-MTP binding inhibitor in HepG2 cells

    PMID:10769147

    Open questions at the time
    • Residue-level mapping of the two domains not defined here
    • Relative contribution of each domain in vivo unquantified
  4. 2001 High

    Explained how lipid context modulates MTP function by showing MTP forms ER-luminal MTP-lipid complexes whose phospholipid charge tunes apoB affinity.

    Evidence In vitro lipid-binding/interaction assays and microsomal fractionation across COS, HepG2, and mouse liver

    PMID:11427523

    Open questions at the time
    • Structural basis of charge-dependent affinity change unknown
    • In vivo relevance of complex stoichiometry not established
  5. 2005 High

    Demonstrated the cell-autonomous, tissue-specific requirement for MTTP in intestinal chylomicron assembly and revealed hepatic compensation.

    Evidence Inducible intestine-specific Mttp knockout with EM and in vivo/in vitro secretion assays

    PMID:16354657

    Open questions at the time
    • Mechanism of compensatory hepatic lipogenesis not defined
  6. 2007 High

    Extended MTP function beyond bulk lipoprotein assembly to immune lipid antigen presentation, showing a splice variant transfers PE to CD1d for NKT development.

    Evidence Identification of MTPv1, in vitro PE transfer to CD1d, and MTP antagonist loss-of-function in fetal thymic organ culture

    PMID:17312007

    Open questions at the time
    • In vivo NKT requirement via genetic MTPv1 deletion not shown
    • Structural basis of CD1d lipid loading by MTP unresolved
  7. 2008 High

    Defined post-transcriptional control of MTP, showing IRE1β selectively degrades MTP mRNA in enterocytes to limit chylomicron output.

    Evidence Ire1b-/- mice with diet challenge, primary enterocytes, and siRNA knockdown

    PMID:18460335

    Open questions at the time
    • Cleavage specificity determinants on MTP mRNA not mapped
    • Tissue restriction mechanism (intestine vs liver) unexplained
  8. 2008 Medium

    Linked a common MTTP promoter polymorphism to allele-specific transcription via differential SREBP1a binding.

    Evidence Promoter-reporter assays and EMSA in Huh-7 cells

    PMID:17854051

    Open questions at the time
    • In vivo physiological impact of the -164T>C allele not established
    • Whether SREBP1a binding is causally repressive untested in vivo
  9. 2010 High

    Connected the circadian clock to lipoprotein rhythms by defining a CLOCK→SHP→MTP transcriptional repression axis.

    Evidence Clock-mutant and Shp-/- mice, promoter binding, knockdown, and SHP rescue of hypertriglyceridemia

    PMID:20674862

    Open questions at the time
    • Quantitative contribution of this axis to total diurnal MTP variation unclear
  10. 2010 Medium

    Implicated epigenetic silencing of MTTP in diet-induced NAFLD and showed it is pharmacologically reversible.

    Evidence Bisulfite sequencing and berberine intervention in high-fat-diet rats

    PMID:20567026

    Open questions at the time
    • Methyltransferase/demethylase responsible not identified
    • Causality of methylation vs expression not separated from confounders
  11. 2012 Medium

    Defined NR2F1/NCoR1 as a corepressor module antagonizing HNF4α/HNF1α synergy at the MTTP promoter.

    Evidence Promoter-reporter, EMSA, and TF co-transfection in intestinal cells

    PMID:22357705

    Open questions at the time
    • In vivo confirmation of NR2F1 repression lacking
    • Physiological signals controlling NR2F1 occupancy unknown
  12. 2012 High

    Defined the IRE1α-XBP1s-PDI arm as a hepatic regulator of MTP activity controlling ER lipid partitioning into VLDL.

    Evidence Hepatocyte-specific Ire1α knockout with MTP activity, lipogenesis, apoB, and PDI readouts

    PMID:23040069

    Open questions at the time
    • Whether PDI level is the sole limiting factor for MTP activity not isolated
  13. 2012 Medium

    Mapped the lipid-transfer catalytic region by showing ABL mutations Y528H/R540C abolish transfer while preserving PDI and apoB binding.

    Evidence Transient expression in COS-7 with lipid-transfer assays and co-IP of mutant panel

    PMID:25108285

    Open questions at the time
    • No high-resolution structure of the catalytic domain provided
    • Single-lab activity assay without orthogonal confirmation
  14. 2012 Medium

    Separated ER retention from function, showing PDI binding and lipid transfer are dispensable for MTTP ER localization.

    Evidence Minigene splicing reporters, PDI co-IP, immunofluorescence, and biopsy transfer assays

    PMID:22236406

    Open questions at the time
    • ER retention signal/determinant not identified
    • Single-lab study
  15. 2014 High

    Placed MTP under insulin-sensitive transcriptional control via FoxO6, linking insulin resistance to hypertriglyceridemia.

    Evidence Transgenic/knockdown and db/db mouse models, promoter mutagenesis, and primary human hepatocytes

    PMID:24437489

    Open questions at the time
    • Interplay between FoxO6 and other MTP regulators not integrated
  16. 2015 Medium

    Identified a SAP18/TRIB1/mSin3A regulatory module occupying MTTP regulatory sequences to set hepatic expression and plasma lipids.

    Evidence Yeast two-hybrid, adenoviral gain/loss in mouse liver, and ChIP

    PMID:25921304

    Open questions at the time
    • Direct vs indirect regulation of MTTP by this complex not fully resolved
    • Single-lab study
  17. 2015 Medium

    Revealed a non-ER, lipid-droplet-associated localization of MTP in adipocytes and steatotic hepatocytes, though without a defined droplet-export function.

    Evidence Immunofluorescence, fractionation, and MTP inhibitor treatment across 3T3-L1 and human liver

    PMID:26267806

    Open questions at the time
    • Functional role of droplet-localized MTP unknown
    • Mechanism of ER-to-droplet redistribution undefined
  18. 2017 High

    Provided isogenic genetic proof of cell-autonomous MTTP requirement in human hepatocytes and cardiomyocytes via CRISPR rescue.

    Evidence Patient MTTPR46G iPSC-derived cells with CRISPR correction and apoB/lipid/death readouts

    PMID:28514664

    Open questions at the time
    • Why cardiomyocytes are particularly vulnerable to lipid accumulation not mechanistically resolved
  19. 2020 High

    Identified PRAP1 as a TG-binding cofactor forming a ternary complex with MTTP required for efficient apoB-lipoprotein assembly and dietary lipid absorption.

    Evidence In vitro ternary complex reconstitution, E85V mutagenesis, and PRAP1-KO/knock-in mice on high-fat diet

    PMID:33168624

    Open questions at the time
    • Stoichiometry and structural arrangement of the MTTP-PRAP1-TG complex unresolved
  20. 2020 High

    Dissociated steatosis from insulin resistance by showing MTTP-loss-driven DAG compartmentalization, not lipid mass, determines hepatic insulin sensitivity.

    Evidence Liver-specific Mttp KO mice with clamps, subcellular DAG fractionation, and PKCε assays

    PMID:32907986

    Open questions at the time
    • Determinants of DAG partitioning between droplets and plasma membrane not defined
  21. 2021 Medium

    Connected lipid-overload oxidative stress to MTP suppression through a PKCδ-HNF4α axis blocking HNF4α nuclear entry.

    Evidence In vivo croaker and in vitro hepatocyte models with PKCδ inhibitor and NAC rescue

    PMID:34116177

    Open questions at the time
    • Mammalian confirmation limited
    • Direct PKCδ-HNF4α phosphorylation event not demonstrated
  22. 2021 Medium

    Showed environmental cadmium raises MTTP protein stability via IP3R-Ca2+-dependent lysosomal deacidification and proteasomal inhibition, elevating TG secretion.

    Evidence Pharmacological dissection (MG132, CQ, BAPTA, 2-APB, CDN1163) with MTTP/TG readouts in HepG2

    PMID:34516972

    Open questions at the time
    • E3 ligase/degradation machinery for MTTP not identified
    • Single-lab study
  23. 2022 Medium

    Revealed a non-canonical extracellular role: adipocyte exosomal MTTP-PRAP1 complexes suppress ferroptosis to drive colorectal cancer chemoresistance.

    Evidence Exosome isolation, MTTP-PRAP1 co-IP, knockdown/inhibitor, organoids, and obese-mouse tumor model

    PMID:35978266

    Open questions at the time
    • Mechanism of MTTP secretion into exosomes unclear
    • Link from MTTP-PRAP1 to ZEB1/GPX4/xCT not fully mechanistic

Open questions

Synthesis pass · forward-looking unresolved questions
  • How MTTP's catalytic and chaperone domains are structurally arranged and coordinate with PRAP1 and ER-luminal lipid complexes during lipoprotein assembly remains unresolved.
  • No high-resolution structure of MTTP in the timeline
  • Stoichiometry of MTTP-lipid and MTTP-PRAP1-TG complexes undefined
  • Mechanism of ER-to-lipid-droplet and exosomal redistribution unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 4 GO:0140104 molecular carrier activity 3 GO:0044183 protein folding chaperone 1
Localization
GO:0005783 endoplasmic reticulum 3 GO:0005811 lipid droplet 1
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-8963743 Digestion and absorption 2
Partners
APOBCD1DPDIPRAP1
Complex memberships
MTP-PDI heterodimerMTTP-PRAP1-TG ternary complex

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 Small molecule inhibitors of MTP prevent assembly and secretion of apolipoprotein B-containing lipoproteins in rodent models, establishing MTP as essential for VLDL/chylomicron production and demonstrating that pharmacological inhibition normalizes plasma lipoprotein levels in WHHL rabbits. High-throughput screening for MTP inhibitors; in vivo treatment of rodent models and WHHL rabbits with compound 9 Science High 9784135
1999 Hepatic overexpression of MTP via recombinant adenovirus in mice results in increased microsomal triglyceride transfer activity, elevated plasma TG, and significantly higher VLDL-TG and VLDL-apoB secretion rates, establishing MTP as rate-limiting for VLDL apoB secretion under basal conditions. Adenoviral hepatic overexpression of MTP in C57BL/6 mice; in vivo measurement of hepatic TG secretion rates and VLDL apoB secretion Journal of lipid research High 10553017
2000 MTP physically interacts with apoB, and a compound (AGI-S17) that specifically inhibits apoB-MTP binding (without affecting MTP lipid transfer activity) reduces apoB secretion by 70-85% in HepG2 cells, identifying two functionally independent domains in MTP: an apoB-binding (chaperone) domain and a lipid transfer domain. Competitive binding assays with apoB peptides and MTP; co-immunoprecipitation in HepG2 cells; selective inhibitor (AGI-S17 vs BMS-200150); apoB secretion measurement by pulse-chase Biochemistry High 10769147
2001 MTP binds lipid vesicles to form stable MTP-lipid complexes in the ER lumen; binding of MTP to zwitterionic phospholipids increases its affinity for apoB100 2–4-fold, while negatively charged lipids decrease apoB-MTP interactions. Stable MTP-lipid complexes are detected in microsomal fractions of COS cells, HepG2 cells, and mouse liver. In vitro lipid binding and protein-protein interaction assays; ultracentrifugation of microsomal contents; binding affinity measurements with apoB truncation constructs The Journal of biological chemistry High 11427523
2005 Conditional intestine-specific deletion of Mttp in villus enterocytes abolishes chylomicron assembly and secretion, causes enterocyte lipid droplet accumulation (steatorrhea), and dramatically reduces apoB48 secretion; hepatic lipogenesis and VLDL secretion increase compensatorily, establishing MTTP as essential for intestinal chylomicron assembly. Tamoxifen-inducible intestine-specific Cre-lox knockout (Mttp-IKO); electron microscopy; in vivo chylomicron secretion assays; primary enterocyte apoB48 secretion The Journal of biological chemistry High 16354657
2007 MTP (via a novel splice variant MTPv1 expressed from an alternate promoter in thymocytes) transfers phosphatidylethanolamine to CD1d in vitro and is required for NKT cell development; MTP inhibition in fetal thymic organ culture abolishes CD1d tetramer-positive cell generation and IL-4 production, while CD1d surface expression is unaffected. PCR/Northern analysis identifying MTPv1; Edman degradation of isolated MTPv1; in vitro phospholipid transfer to CD1d; fetal thymic organ culture with MTP antagonists; flow cytometry for CD1d tetramers The Journal of experimental medicine High 17312007
2008 IRE1β (but not IRE1α) selectively degrades MTP mRNA via increased posttranscriptional degradation in enterocytes, thereby reducing intestinal MTP expression and chylomicron production; Ire1b−/− mice secrete more chylomicrons and express more intestinal (but not hepatic) MTP. Ire1b−/− mouse model; diet challenge; primary enterocyte isolation; cell culture siRNA knockdown of IRE1β; quantification of MTP mRNA stability and chylomicron secretion Cell metabolism High 18460335
2010 The circadian clock gene CLOCK upregulates SHP (NROB2) expression by binding to its E-box; SHP then suppresses MTP expression by binding to HNF4α/LRH-1 at the MTP promoter, establishing a CLOCK→SHP→MTP axis that drives diurnal oscillation of plasma triglyceride-rich lipoproteins. Clock mutant mice (Clock mt/mt); CLOCK knockdown; SHP knockout mice (Shp−/−); serum-shock cyclic expression assay; promoter binding and siRNA experiments; rescue of hypertriglyceridemia by SHP expression Cell metabolism High 20674862
2012 The IRE1α-XBP1s arm of the UPR regulates hepatic VLDL assembly: hepatocyte-specific Ire1α deletion reduces MTP activity (without affecting TG synthesis or apoB synthesis/secretion) due to decreased PDI expression, impairing lipid partitioning into the ER lumen and TG-rich VLDL assembly. Hepatocyte-specific Ire1α knockout mice; MTP activity assays; de novo lipogenesis measurements; apoB synthesis/secretion assays; PDI expression analysis Cell metabolism High 23040069
2012 NR2F1 suppresses synergistic activation of the MTTP promoter by HNF-4α/HNF-1α by binding to a direct repeat 1 (DR1) element and recruiting nuclear receptor corepressor 1 (NCoR1), without affecting activities of the individual transcription factors; HNF-4α is required for basal MTTP expression. MTTP promoter-reporter (luciferase) assays; EMSA; co-transfection of transcription factors in intestinal cell lines Journal of lipid research Medium 22357705
2014 FoxO6 directly binds the MTP promoter and stimulates MTP expression and VLDL-TG secretion; insulin inhibits this by phosphorylating FoxO6 to disable DNA binding. Hepatic FoxO6 inhibition in insulin-resistant db/db mice suppresses MTP expression and reduces hypertriglyceridemia. Transgenic and knockdown mouse models; promoter binding assays (ChIP-like); MTP promoter-reporter assays with FoxO6 site mutations; primary human hepatocytes; insulin signaling assays in db/db mice Endocrinology High 24437489
2015 SAP18 is a novel binding partner of TRIB1 that regulates MTTP expression; SAP18 and TRIB1 co-occupy MTTP regulatory sequences along with mSin3A; SAP18 knockdown decreases and overexpression increases hepatic MTTP expression and plasma lipid levels. Yeast two-hybrid screen; adenoviral overexpression/knockdown in mouse liver; chromatin immunoprecipitation; transcriptome analysis Journal of lipid research Medium 25921304
2017 Loss of MTTP activity (MTTPR46G mutation) in iPSC-derived hepatocytes and cardiomyocytes abolishes apoB secretion and causes intracellular lipid accumulation and increased cell death in cardiomyocytes; correction of the mutation by CRISPR/Cas9 rescues these phenotypes, demonstrating a cell-autonomous requirement for MTTP in both cell types. Patient-derived iPSCs with MTTPR46G mutation; differentiation to hepatocytes and cardiomyocytes; CRISPR/Cas9 correction; apoB secretion assays; lipid staining; cell death assays Cell reports High 28514664
2020 PRAP1 is a novel lipid-binding protein that directly binds TG and forms a ternary complex with TG and MTTP in the ER; a single amino acid mutation (E85V) that disrupts ternary complex formation impairs MTTP-mediated apoB-containing lipoprotein assembly and secretion. PRAP1-deficient and E85V knock-in mice show reduced lipid absorption and resistance to diet-induced obesity. Co-localization in ER; in vitro lipid transfer assays; ternary complex formation assays; site-directed mutagenesis (E85V); PRAP1-KO and knock-in mouse models; high-fat diet challenge The Journal of biological chemistry High 33168624
2020 In liver-specific MTTP knockout (L-Mttp−/−) mice, hepatic steatosis does not cause insulin resistance in young mice because DAG accumulates in lipid droplets rather than the plasma membrane; in aged L-Mttp−/− mice, plasma membrane sn-1,2-DAG content increases with PKCε activation and hepatic insulin resistance, demonstrating that intracellular DAG compartmentalization determines insulin sensitivity independent of steatosis. Liver-specific Mttp KO mice; hyperinsulinemic-euglycemic clamps; subcellular DAG fractionation; PKCε activation assay; mitochondrial uncoupler treatment Journal of lipid research High 32907986
2008 The MTTP promoter polymorphism -164T>C mediates allele-specific promoter activity: the common -164T allele shows lower transcriptional activity than the rare -164C allele. EMSA revealed higher binding of transcription factor SREBP1a to the -164T probe, suggesting that SREBP1a binding to this site reduces MTTP promoter activity. Promoter-reporter (luciferase) assays in Huh-7 hepatoma cells; EMSA with SREBP1a Human mutation Medium 17854051
2005 Oleic acid directly stimulates MTP gene transcription in HepG2 cells through a region between -116 and -109 bp of the MTP promoter in an SRE-independent manner; palmitate, arachidonic acid, and linoleic acid do not stimulate MTP transcription. MTP promoter-luciferase reporter assays with deletion/mutation constructs in HepG2 cells; long-term oleic acid treatment with MTP mRNA quantification Biochemistry Medium 15723548
2011 Hepatitis B virus (HBV) infection suppresses MTP mRNA and protein expression in a dose-dependent manner in transfected HepG2 cells, leading to decreased apoB expression and secretion. HBV infectious clone (pHBV1.3) transfection in HepG2 cells; RT-PCR and western blot for MTP and apoB Lipids in health and disease Low 22074108
2011 Acute insulin suppression of apoB secretion occurs independently of MTP: insulin does not alter hepatic MTP mRNA levels or lipid transfer activity acutely (2h) in vivo, and overexpression of MTP does not abrogate insulin-mediated suppression of apoB secretion in primary rat hepatocytes. In vivo insulin injection in apobec-1−/− mice; adenoviral MTP overexpression in primary rat hepatocytes; MTP lipid transfer activity assays; apoB secretion measurement Biochemical and biophysical research communications Medium 21316344
2012 Missense mutations Y528H and R540C in MTTP cause abetalipoproteinemia by abolishing lipid-transfer activity while retaining normal binding to PDI and apoB; N649S partially reduces activity; G264R retains full activity but causes ABL via a frameshift, identifying the region containing residues 528-540 as critical for the lipid-transfer catalytic domain. Transient expression in COS-7 cells; MTP lipid-transfer activity assays; co-immunoprecipitation with PDI and apoB constructs Biochimica et biophysica acta Medium 25108285
2012 MTTP splicing mutations causing exon deletions (Δ6 and Δ10) produce truncated proteins that fail to bind PDI and lack triglyceride transfer activity, but still localize normally to the ER, demonstrating that PDI binding and lipid transfer activity are not required for ER retention of MTTP. Minigene splicing reporter assays; transfection in HepG2/HeLa cells; PDI co-immunoprecipitation; ER localization by immunofluorescence; triglyceride transfer activity assay on duodenal biopsies Human mutation Medium 22236406
2015 MTP associates with cytosolic lipid droplet surfaces in adipocytes and fatty liver hepatocytes, redistributing from the juxtanuclear ER region to lipid droplets during 3T3-L1 adipocyte differentiation; MTP co-localizes with but does not overlap with perilipin 2 on droplets; inhibition of MTP activity does not affect TG export via lipolysis or secretion from adipocytes. Immunofluorescence microscopy; subcellular fractionation; MTP inhibitor treatment; lipid droplet isolation; differentiation time-course in 3T3-L1 cells PloS one Medium 26267806
2010 High-fat diet-induced NAFLD in rats is associated with elevated DNA methylation of the MTTP promoter (at specific CpG sites including -113 and -20), which negatively correlates with MTTP expression; berberine reverses this methylation and restores MTTP expression and hepatic TG export. Bisulfite sequencing of MTTP promoter CpG sites; MTTP mRNA quantification; hepatic TG secretion measurement in high-fat diet rats treated with berberine Journal of lipid research Medium 20567026
2021 Lipid overload activates PKCδ via oxidative stress, which prevents HNF4α nuclear entry, reducing MTP transcription and impairing VLDL secretion in hepatocytes; PKCδ inhibitor (Go6983) or ROS scavenger (NAC) partially rescues MTP expression and VLDL secretion. In vivo high-fat diet in large yellow croaker; in vitro oleic acid treatment of hepatocytes; PKCδ inhibitor and NAC treatments; HNF4α nuclear localization assays; MTP expression and VLDL secretion measurements Free radical biology & medicine Medium 34116177
2022 Adipocyte-derived exosomal MTTP enters CRC cells and forms a complex with PRAP1 that inhibits ZEB1 expression and upregulates GPX4 and xCT, reducing polyunsaturated fatty acid ratios and lipid ROS levels to suppress ferroptosis and promote chemoresistance to oxaliplatin. Exosome isolation and characterization; co-IP of MTTP-PRAP1 complex; siRNA knockdown and MTTP inhibitor experiments; organoid models; obese mouse tumor implantation model; lipid ROS measurement Advanced science Medium 35978266
2021 Cadmium exposure increases MTTP protein stability by inhibiting both proteasomal and lysosomal protein degradation pathways; the lysosomal pathway is disrupted via ER Ca2+ release through IP3R, and this Ca2+-dependent lysosomal deacidification leads to MTTP accumulation and elevated TG secretion. siRNA knockdown of MTTP; co-treatment with proteasome inhibitor MG132 and lysosome inhibitor CQ; intracellular Ca2+ chelation (BAPTA/AM); IP3R inhibition (2-APB); SERCA activation (CDN1163); TG and MTTP protein measurement in HepG2 cells Chemico-biological interactions Medium 34516972

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 An MTP inhibitor that normalizes atherogenic lipoprotein levels in WHHL rabbits. Science (New York, N.Y.) 226 9784135
2022 Adipocyte-Derived Exosomal MTTP Suppresses Ferroptosis and Promotes Chemoresistance in Colorectal Cancer. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 207 35978266
2012 IRE1α-XBP1s induces PDI expression to increase MTP activity for hepatic VLDL assembly and lipid homeostasis. Cell metabolism 189 23040069
2003 CP-346086: an MTP inhibitor that lowers plasma cholesterol and triglycerides in experimental animals and in humans. Journal of lipid research 157 12837854
2001 Secretion of hepatocyte apoB is inhibited by the flavonoids, naringenin and hesperetin, via reduced activity and expression of ACAT2 and MTP. Journal of lipid research 149 11352979
2010 Diurnal regulation of MTP and plasma triglyceride by CLOCK is mediated by SHP. Cell metabolism 146 20674862
1999 Hepatic overexpression of microsomal triglyceride transfer protein (MTP) results in increased in vivo secretion of VLDL triglycerides and apolipoprotein B. Journal of lipid research 123 10553017
2010 Berberine reduces methylation of the MTTP promoter and alleviates fatty liver induced by a high-fat diet in rats. Journal of lipid research 122 20567026
2008 IRE1beta inhibits chylomicron production by selectively degrading MTP mRNA. Cell metabolism 108 18460335
2013 Betaine attenuates hepatic steatosis by reducing methylation of the MTTP promoter and elevating genomic methylation in mice fed a high-fat diet. The Journal of nutritional biochemistry 106 24456734
2005 Compensatory increase in hepatic lipogenesis in mice with conditional intestine-specific Mttp deficiency. The Journal of biological chemistry 102 16354657
2006 Ancylostoma caninum MTP-1, an astacin-like metalloprotease secreted by infective hookworm larvae, is involved in tissue migration. Infection and immunity 93 16428741
2011 Viral genotype-specific role of PNPLA3, PPARG, MTTP, and IL28B in hepatitis C virus-associated steatosis. Journal of hepatology 86 21236304
2005 No association between microsomal triglyceride transfer protein (MTP) haplotype and longevity in humans. Proceedings of the National Academy of Sciences of the United States of America 83 15911777
2005 Effect of combining the larval antigens Ancylostoma secreted protein 2 (ASP-2) and metalloprotease 1 (MTP-1) in protecting hamsters against hookworm infection and disease caused by Ancylostoma ceylanicum. Vaccine 67 15837211
1998 Membrane-type matrix metalloproteinase-1(MT1-MTP) gene is overexpressed in highly invasive hepatocellular carcinomas. Journal of hepatology 65 9514536
2005 JTT-130, a microsomal triglyceride transfer protein (MTP) inhibitor lowers plasma triglycerides and LDL cholesterol concentrations without increasing hepatic triglycerides in guinea pigs. BMC cardiovascular disorders 62 16188040
2007 MTP regulated by an alternate promoter is essential for NKT cell development. The Journal of experimental medicine 55 17312007
2007 MTP inhibition as a treatment for dyslipidaemias: time to deliver or empty promises? Expert opinion on therapeutic targets 53 17227233
2000 Decreased secretion of ApoB follows inhibition of ApoB-MTP binding by a novel antagonist. Biochemistry 53 10769147
1996 Safety and immunogenicity of Env 2-3, a human immunodeficiency virus type 1 candidate vaccine, in combination with a novel adjuvant, MTP-PE/MF59. NIAID AIDS Vaccine Evaluation Group. AIDS research and human retroviruses 53 8744579
2014 Muramyl tripeptide-phosphatidyl ethanolamine encapsulated in liposomes (L-MTP-PE) in the treatment of osteosarcoma. Advances in experimental medicine and biology 52 24924182
1993 Liposome-encapsulated MTP-PE: a novel biologic agent for cancer therapy. Journal of immunotherapy with emphasis on tumor immunology : official journal of the Society for Biological Therapy 51 8280710
2020 Restoring mitochondrial superoxide levels with elamipretide (MTP-131) protects db/db mice against progression of diabetic kidney disease. The Journal of biological chemistry 50 32277051
2013 Rapid regression of atherosclerosis with MTP inhibitor treatment. Atherosclerosis 48 23332773
2005 Mutations in MTP gene in abeta- and hypobeta-lipoproteinemia. Atherosclerosis 47 15910857
2022 Tunable Microgel-Templated Porogel (MTP) Bioink for 3D Bioprinting Applications. Advanced healthcare materials 44 35037731
2010 Mechanisms underlying different responses of plasma triglyceride to high-fat diets in hamsters and mice: roles of hepatic MTP and triglyceride secretion. Biochemical and biophysical research communications 43 20510883
2004 Inhibitory activity of diacylglycerol acyltransferase (DGAT) and microsomal triglyceride transfer protein (MTP) by the flavonoid, taxifolin, in HepG2 cells: potential role in the regulation of apolipoprotein B secretion. Atherosclerosis 43 15380446
2019 Lomitapide and Mipomersen-Inhibiting Microsomal Triglyceride Transfer Protein (MTP) and apoB100 Synthesis. Current atherosclerosis reports 40 31741187
2004 Thermophilic, reversible gamma-resorcylate decarboxylase from Rhizobium sp. strain MTP-10005: purification, molecular characterization, and expression. Journal of bacteriology 39 15466039
2013 MTTP polymorphisms and susceptibility to non-alcoholic fatty liver disease in a Han Chinese population. Liver international : official journal of the International Association for the Study of the Liver 37 23738963
2021 Comprehensive genome wide identification and expression analysis of MTP gene family in tomato (Solanum lycopersicum) under multiple heavy metal stress. Saudi journal of biological sciences 36 34866994
2008 Microsomal triglyceride transfer protein (MTP) -493G/T gene polymorphism contributes to fat liver accumulation in HCV genotype 3 infected patients. Journal of viral hepatitis 36 18482281
2005 Current biology of MTP: implications for selective inhibition. Current topics in medicinal chemistry 36 15857311
2004 Ferroportin/IREG-1/MTP-1/SLC40A1 modulates the uptake of iron at the apical membrane of enterocytes. Gut 36 14684575
2020 PRAP1 is a novel lipid-binding protein that promotes lipid absorption by facilitating MTTP-mediated lipid transport. The Journal of biological chemistry 35 33168624
2014 Intestine-specific MTP and global ACAT2 deficiency lowers acute cholesterol absorption with chylomicrons and HDLs. Journal of lipid research 35 25030663
2010 Long-chain 3-hydroxy fatty acids accumulating in LCHAD and MTP deficiencies induce oxidative stress in rat brain. Neurochemistry international 35 20381565
2000 Microsomal triglyceride transfer protein (MTP) gene mutations in Canadian subjects with abetalipoproteinemia. Human mutation 35 10679949
2017 Lack of MTTP Activity in Pluripotent Stem Cell-Derived Hepatocytes and Cardiomyocytes Abolishes apoB Secretion and Increases Cell Stress. Cell reports 34 28514664
2014 FoxO6 integrates insulin signaling with MTP for regulating VLDL production in the liver. Endocrinology 33 24437489
2012 Molecular and functional analysis of two new MTTP gene mutations in an atypical case of abetalipoproteinemia. Journal of lipid research 33 22236406
2011 Mitochondria-targeted peptide MTP-131 alleviates mitochondrial dysfunction and oxidative damage in human trabecular meshwork cells. Investigative ophthalmology & visual science 33 21697135
2012 Impaired fatty acid oxidation in a Drosophila model of mitochondrial trifunctional protein (MTP) deficiency. Biochemical and biophysical research communications 32 22342726
2009 Lipoprotein metabolism mediates the association of MTP polymorphism with beta-cell dysfunction in healthy subjects and in nondiabetic normolipidemic patients with nonalcoholic steatohepatitis. The Journal of nutritional biochemistry 32 19733470
1994 Effect of MTP-PE liposomes and interleukin-7 on induction of antibody and cell-mediated immune responses to a recombinant HIV-envelope protein. Journal of acquired immune deficiency syndromes 32 8021814
2019 Molecular characterization and expression dynamics of MTP genes under various spatio-temporal stages and metal stress conditions in rice. PloS one 31 31136613
2015 MTTP-297H polymorphism reduced serum cholesterol but increased risk of non-alcoholic fatty liver disease-a cross-sectional study. BMC medical genetics 31 26458397
2015 Evaluation of the role of Mycobacterium tuberculosis pili (MTP) as an adhesin, invasin, and cytokine inducer of epithelial cells. The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases 31 26748229
1988 Modulation of interferon-gamma-induced major histocompatibility (MHC) and CD14 antigen changes by lipophilic muramyltripeptide MTP-PE in human monocytes. Cellular immunology 31 2460255
2021 Berberine ameliorates nonalcoholic fatty liver disease by decreasing the liver lipid content via reversing the abnormal expression of MTTP and LDLR. Experimental and therapeutic medicine 30 34504563
2013 Molecular cloning and characterisation of in vitro immune response against astacin-like metalloprotease Ace-MTP-2 from Ancylostoma ceylanicum. Experimental parasitology 30 23376445
2012 NR2F1 disrupts synergistic activation of the MTTP gene transcription by HNF-4α and HNF-1α. Journal of lipid research 28 22357705
2002 Microsomal triglyceride transfer protein (MTP) inhibitors: discovery of clinically active inhibitors using high-throughput screening and parallel synthesis paradigms. Current opinion in drug discovery & development 28 12197314
2021 MTP deficiency caused by HADHB mutations: Pathophysiology and clinical manifestations. Molecular genetics and metabolism 27 33744096
2021 Lipid overload impairs hepatic VLDL secretion via oxidative stress-mediated PKCδ-HNF4α-MTP pathway in large yellow croaker (Larimichthys crocea). Free radical biology & medicine 26 34116177
2019 Genome-wide identification and characterization of the metal tolerance protein (MTP) family in grape (Vitis vinifera L.). 3 Biotech 26 31065499
2014 Mycobacterium tuberculosis pili (MTP), a putative biomarker for a tuberculosis diagnostic test. Tuberculosis (Edinburgh, Scotland) 26 24721207
2014 Microsomal transfer protein (MTP) inhibition-a novel approach to the treatment of homozygous hypercholesterolemia. Annals of medicine 26 24987866
1998 Identification of two polymorphisms in the promoter of the microsomal triglyceride transfer protein (MTP) gene: lack of association with lipoprotein profiles. Journal of lipid research 26 9831631
2023 Genome-wide identification and expression analysis of metal tolerance protein (MTP) gene family in soybean (Glycine max) under heavy metal stress. Molecular biology reports 25 36653731
2012 Novel mutations in SAR1B and MTTP genes in Tunisian children with chylomicron retention disease and abetalipoproteinemia. Gene 25 23043934
2020 Identification of MTP gene family in tea plant (Camellia sinensis L.) and characterization of CsMTP8.2 in manganese toxicity. Ecotoxicology and environmental safety 24 32800239
2016 Disturbance of mitochondrial functions provoked by the major long-chain 3-hydroxylated fatty acids accumulating in MTP and LCHAD deficiencies in skeletal muscle. Toxicology in vitro : an international journal published in association with BIBRA 24 27371118
2015 Sin3A-associated protein, 18 kDa, a novel binding partner of TRIB1, regulates MTTP expression. Journal of lipid research 24 25921304
2009 A non-synonymous mutation in a conserved site of the MTTP gene is strongly associated with protein activity and fatty acid profile in pigs. Animal genetics 24 19496770
2008 Functional analysis of promoter variants in the microsomal triglyceride transfer protein (MTTP) gene. Human mutation 24 17854051
2001 Binding of microsomal triglyceride transfer protein to lipids results in increased affinity for apolipoprotein B: evidence for stable microsomal MTP-lipid complexes. The Journal of biological chemistry 24 11427523
2017 Protective effect of mitochondria‑targeted peptide MTP‑131 against oxidative stress‑induced apoptosis in RGC‑5 cells. Molecular medicine reports 23 28260075
2014 Novel missense MTTP gene mutations causing abetalipoproteinemia. Biochimica et biophysica acta 23 25108285
2007 Conditional intestinal lipotoxicity in Apobec-1-/- Mttp-IKO mice: a survival advantage for mammalian intestinal apolipoprotein B mRNA editing. The Journal of biological chemistry 23 17855359
2006 Biochemical and genetic analysis of the gamma-resorcylate (2,6-dihydroxybenzoate) catabolic pathway in Rhizobium sp. strain MTP-10005: identification and functional analysis of its gene cluster. Journal of bacteriology 23 17158677
1995 Comparative studies of cytotoxicity and the release of TNF-alpha, nitric oxide, and eicosanoids of liver macrophages treated with lipopolysaccharide and liposome-encapsulated MTP-PE. Journal of immunology (Baltimore, Md. : 1950) 23 7650390
2022 Long Noncoding RNA lncRHL Regulates Hepatic VLDL Secretion by Modulating hnRNPU/BMAL1/MTTP Axis. Diabetes 22 35771993
2012 Distinguishing between longevity and buffered-deleterious genotypes for exceptional human longevity: the case of the MTP gene. The journals of gerontology. Series A, Biological sciences and medical sciences 22 22496539
2005 Hypolipidemic action of the SERM acolbifene is associated with decreased liver MTP and increased SR-BI and LDL receptors. Journal of lipid research 22 15741653
2002 Regulation of MTP expression in developing swine. Journal of lipid research 22 12177174
2020 Membrane-bound sn-1,2-diacylglycerols explain the dissociation of hepatic insulin resistance from hepatic steatosis in MTTP knockout mice. Journal of lipid research 21 32907986
2016 Camphene, a Plant Derived Monoterpene, Exerts Its Hypolipidemic Action by Affecting SREBP-1 and MTP Expression. PloS one 21 26784701
2016 MTP Gene Variants and Response to Lomitapide in Patients with Homozygous Familial Hypercholesterolemia. Journal of atherosclerosis and thrombosis 21 27170061
1992 Liposomes containing muramyl tripeptide phosphatidylethanolamine (MTP-PE) are excellent adjuvants for induction of an immune response to protein and tumor antigens. Journal of leukocyte biology 21 1431559
2018 Fatal pitfalls in newborn screening for mitochondrial trifunctional protein (MTP)/long-chain 3-Hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency. Orphanet journal of rare diseases 20 30029694
2013 Mechanisms underlying hypertriglyceridemia in rats with monosodium L-glutamate-induced obesity: evidence of XBP-1/PDI/MTP axis activation. Biochemical and biophysical research communications 20 24333444
2011 A severe form of abetalipoproteinemia caused by new splicing mutations of microsomal triglyceride transfer protein (MTTP). Human mutation 20 21394827
2005 Oleate-mediated stimulation of microsomal triglyceride transfer protein (MTP) gene promoter: implications for hepatic MTP overexpression in insulin resistance. Biochemistry 20 15723548
2015 Microsomal Triglyceride Transfer Protein (MTP) Associates with Cytosolic Lipid Droplets in 3T3-L1 Adipocytes. PloS one 19 26267806
2012 Intestine-specific Mttp deletion decreases mortality and prevents sepsis-induced intestinal injury in a murine model of Pseudomonas aeruginosa pneumonia. PloS one 19 23145105
2011 HBV inhibits apoB production via the suppression of MTP expression. Lipids in health and disease 19 22074108
2023 QTL-seq and transcriptomic integrative analyses reveal two positively regulated genes that control the low-temperature germination ability of MTP-maize introgression lines. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 18 37093290
2014 Correlation between MTP -493G>T polymorphism and non-alcoholic fatty liver disease risk: a meta-analysis. Genetics and molecular research : GMR 18 25501226
2011 Acute suppression of apo B secretion by insulin occurs independently of MTP. Biochemical and biophysical research communications 18 21316344
2010 Allele-specific regulation of MTTP expression influences the risk of ischemic heart disease. Journal of lipid research 18 19546343
2007 Nonalcoholic steatohepatitis (NASH) in ob/ob mice treated with yo jyo hen shi ko (YHK): effects on peroxisome proliferator-activated receptors (PPARs) and microsomal triglyceride transfer protein (MTP). Digestive diseases and sciences 18 17394061
1994 Liposomal muramyl tripeptide phosphatidylethanolamine (MTP-PE) promotes haemopoietic recovery in irradiated mouse. International journal of radiation biology 18 7908934
2021 Cadmium induces triglyceride levels via microsomal triglyceride transfer protein (MTTP) accumulation caused by lysosomal deacidification regulated by endoplasmic reticulum (ER) Ca2+ homeostasis. Chemico-biological interactions 16 34516972
2014 MTP -493G>T polymorphism and susceptibility to nonalcoholic fatty liver disease: a meta-analysis. DNA and cell biology 16 24588800
2008 The influence of polymorphism of -493G/T MTP gene promoter and metabolic syndrome on lipids, fatty acids and oxidative stress. The Journal of nutritional biochemistry 16 18280132
2004 5-Carboxamido-1,3,2-dioxaphosphorinanes, potent inhibitors of MTP. Bioorganic & medicinal chemistry letters 16 15380200
2012 Rescue of Mtp siRNA-induced hepatic steatosis by DGAT2 siRNA silencing. Journal of lipid research 15 22355095

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