Referencia

PLoS Genet. 2011 Feb 10;7(2):e1001297

Autores

Esmeralda Parra-Peralbo y Joaquim Culí

Resumen

El aumento alarmante en la incidencia de la obesidad y la diabetes experimentado durante las últimas tres décadas hace necesario el estudio de los complejos mecanismos que regulan el almacenaje del aporte calórico sobrante en forma de grasa corporal. El uso de organismos modelo fácilmente manipulables a nivel genético, como Drosophila melanogaster, ha proporcionado importantes avances en este campo. En este trabajo hemos estudiado el mecanismo molecular que media la transferencia de lípidos neutros desde las lipoproteínas circulantes a los tejidos de Drosophila. Nuestro trabajo describe la función crucial de los receptores de lipoforinas (homólogos a los receptores de LDL, VLDL y ApoE de humanos) en la adquisición celular de lípidos neutros. Demostramos que el proceso de lipólisis ocurre extracelularmente de manera similar a como ocurre en los microcapilares de los mamíferos, sugiriendo un papel ancestral de las proteínas de la familia LDLR en el procesamiento extracelular de lipoproteínas.

Descripción

Lipids are constantly shuttled through the body to redistribute energy and metabolites between sites of absorption, storage and catabolism in a complex homeostatic equilibrium. In Drosophila, lipids are transported through the hemolymph in the form of lipoprotein particles, known as lipophorins. The mechanisms by which cells interact with circulating lipophorins and acquire their lipidic cargo are poorly understood. We have found that lipophorin receptor 1 and 2 (lpr1 and lpr2), two partially redundant genes belonging to the Low Density Lipoprotein Receptor (LDLR) family, are essential for the efficient uptake and accumulation of neutral lipids by oocytes and cells of the imaginal discs. Females lacking the lpr2 gene lay eggs with low lipid content and have reduced fertility,
revealing a central role for lpr2 in mediating Drosophila vitellogenesis. lpr1 and lpr2 are transcribed into multiple isoforms. Interestingly, only a subset of these isoforms containing a particular LDLR type A module mediate neutral lipid uptake. Expression of these isoforms induces the extracellular stabilization of lipophorins. Furthermore, our data indicates that endocytosis is not required to mediate the uptake of neutral lipids. These findings suggest a model where lipophorin receptors promote the extracellular lipolysis of lipophorins. This model is reminiscent of the lipolytic processing of triglyceride-rich lipoproteins that occurs at the mammalian capillary endothelium, suggesting an ancient role for LDLR-like proteins in this process.

Imagen artículo Julio

REFERENCIA DEL GRUPO E INVESTIGADOR
Esmeralda Parra-Peralbo ha realizado su tesis doctoral en el grupo dirigido por Joaquim Culi en el Centro Andaluz de Biología del Desarrollo, un centro mixto del CSIC y la UPO. Mediante aproximaciones genéticas y bioquímicas, estudiamos aspectos básicos del metabolismo de las lipoproteínas y sus receptores, utilizando la mosca Drosophila melanogaster como organismo modelo.

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