Multiple functions of microsomal triglyceride transfer protein

Abstract

Microsomal triglyceride transfer protein (MTP) was first identified as a major cellular protein capable of transferring neutral lipids between membrane vesicles. Its role as an essential chaperone for the biosynthesis of apolipoprotein B (apoB)-containing triglyceride-rich lipoproteins was established after the realization that abetalipoproteinemia patients carry mutations in the MTTP gene resulting in the loss of its lipid transfer activity. Now it is known that it also plays a role in the biosynthesis of CD1, glycolipid presenting molecules, as well as in the regulation of cholesterol ester biosynthesis. In this review, we will provide a historical perspective about the identification, purification and characterization of MTP, describe methods used to measure its lipid transfer activity, and discuss tissue expression and function. Finally, we will review the role MTP plays in the assembly of apoB-lipoprotein, the regulation of cholesterol ester synthesis, biosynthesis of CD1 proteins and propagation of hepatitis C virus. We will also provide a brief overview about the clinical potentials of MTP inhibition.

Lipid Absorption Defects in Intestine-specific Microsomal Triglyceride Transfer Protein and ATP-binding Cassette Transporter A1-deficient Mice

“…MTP deficiency in abetalipoproteinemia is associated with markedly lower plasma lipid concentrations, fat-soluble vitamin deficiency, stunted growth, and acanthocytosis (3,4). Previous attempts to generate animal models of abetalipoproteinemia were hampered due to embryonic lethality of Mttp knock-out mice (5).…”

Genetically Modified Animal Models for Lipoprotein Research

“…Dietary cholesterol forms micelles with bail acids in the lumen of the jejunum, which are then transported through NPC1L1. Thereafter, the free cholesterol is esterified by acyl coenzyme A:cholesterol acyltransferase 2 (ACAT2) and chylomicron particles are formed by the packaging of esterified cholesterol, triglyceride, and apolipoprotein B by MTP (Hussain, 2012). NPC1L1 was found by Altman et al (2002).…”

“…Synthesized triglycerides, cholesterol, and apolipoproteins are assembled in chylomicron particles. In the process of chylomicron assembly, MTP assists in binding lipids to apolipoproteins (Hussain, 2012). Since the apoB mRNA editing enzyme (apobec-1) functions at the intestinal wall, chylomicron particles contain apoB-48 as a major apolipoprotein but do not contain apoB-100.…”

Nuevos fármacos para el tratamiento de la hipercolesterolemia

“…En Estados Unidos de Norteamérica y en Europa ha sido autorizado para el tratamiento de la HFHo en adultos mayores de 18 años como terapia coadyudante a una dieta baja en grasas y al tratamiento farmacológico hipolipemiante convencional junto a LDL-aféresis si está disponible 7,8 . La MTP es una proteína esencial para el ensamblaje y secreción de las lipoproteínas de muy baja densidad (VLDL) de origen hepático y de los quilomicrones de origen intestinal 10 . La importancia de esta proteína como objetivo de tratamiento surgió al estudiar los casos con abetalipoproteinemia, una enfermedad rara producida por mutaciones en esta enzima, que demostró que estos pacientes tienen niveles muy bajos de colesterol y triglicéridos 11 .…”