LRP1 controls intracellular cholesterol storage and fatty acid synthesis through modulation of wnt signaling

Jérome Terrand, Véronique Bruban, Li Zhou, Wanfeng Gong, Zeina El Asmar, Petra May, Kai Zurhove, Philipp Haffner, Claude Philippe, Estelle Woldt, Rachel L. Matz, Céline Gracia, Daniel Metzger, Johan Auwerx, Joachim Herz, Philippe Boucher

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

The low-density lipoprotein receptor-related protein LRP1 is a cell surface receptor with functions in diverse physiological pathways, including lipid metabolism. Here we show that LRP1- deficient fibroblasts accumulate high levels ofintracellular cholesterol and cholesteryl-ester when stimulated for adipocyte differentiation. We demonstrate that LRP1 stimulates a canonical Wnt5a signaling pathway that prevents cholesterol accumulation. Moreover, we show that LRP1 is required for lipolysis and stimulates fatty acid synthesis independently ofthe noradrener- gic pathway, through inhibition of GSK3β and its previously unknown target acetyl-CoA carboxylase (ACC). As a result of ACC inhibition, mature LRP1-deficient adipocytes of adult mice are hypotrophic, and lower uptake of fatty acids into adipose tissue leads to their redistribution to the liver. These results establish LRP1 as a novel integrator of adipogenic differentiation and fat storage signals.

Original languageEnglish (US)
Pages (from-to)381-388
Number of pages8
JournalJournal of Biological Chemistry
Volume284
Issue number1
DOIs
StatePublished - Jan 2 2009

Fingerprint

Acetyl-CoA Carboxylase
Cholesterol Esters
Adipocytes
Fatty Acids
Cholesterol
LDL-Receptor Related Proteins
Modulation
LDL Receptors
Lipolysis
Cell Surface Receptors
Fibroblasts
Lipid Metabolism
Liver
Adipose Tissue
Fats
Tissue
Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

LRP1 controls intracellular cholesterol storage and fatty acid synthesis through modulation of wnt signaling. / Terrand, Jérome; Bruban, Véronique; Zhou, Li; Gong, Wanfeng; Asmar, Zeina El; May, Petra; Zurhove, Kai; Haffner, Philipp; Philippe, Claude; Woldt, Estelle; Matz, Rachel L.; Gracia, Céline; Metzger, Daniel; Auwerx, Johan; Herz, Joachim; Boucher, Philippe.

In: Journal of Biological Chemistry, Vol. 284, No. 1, 02.01.2009, p. 381-388.

Research output: Contribution to journalArticle

Terrand, J, Bruban, V, Zhou, L, Gong, W, Asmar, ZE, May, P, Zurhove, K, Haffner, P, Philippe, C, Woldt, E, Matz, RL, Gracia, C, Metzger, D, Auwerx, J, Herz, J & Boucher, P 2009, 'LRP1 controls intracellular cholesterol storage and fatty acid synthesis through modulation of wnt signaling', Journal of Biological Chemistry, vol. 284, no. 1, pp. 381-388. https://doi.org/10.1074/jbc.M806538200
Terrand, Jérome ; Bruban, Véronique ; Zhou, Li ; Gong, Wanfeng ; Asmar, Zeina El ; May, Petra ; Zurhove, Kai ; Haffner, Philipp ; Philippe, Claude ; Woldt, Estelle ; Matz, Rachel L. ; Gracia, Céline ; Metzger, Daniel ; Auwerx, Johan ; Herz, Joachim ; Boucher, Philippe. / LRP1 controls intracellular cholesterol storage and fatty acid synthesis through modulation of wnt signaling. In: Journal of Biological Chemistry. 2009 ; Vol. 284, No. 1. pp. 381-388.
@article{6f32a44e24194805b6b096f4076ae495,
title = "LRP1 controls intracellular cholesterol storage and fatty acid synthesis through modulation of wnt signaling",
abstract = "The low-density lipoprotein receptor-related protein LRP1 is a cell surface receptor with functions in diverse physiological pathways, including lipid metabolism. Here we show that LRP1- deficient fibroblasts accumulate high levels ofintracellular cholesterol and cholesteryl-ester when stimulated for adipocyte differentiation. We demonstrate that LRP1 stimulates a canonical Wnt5a signaling pathway that prevents cholesterol accumulation. Moreover, we show that LRP1 is required for lipolysis and stimulates fatty acid synthesis independently ofthe noradrener- gic pathway, through inhibition of GSK3β and its previously unknown target acetyl-CoA carboxylase (ACC). As a result of ACC inhibition, mature LRP1-deficient adipocytes of adult mice are hypotrophic, and lower uptake of fatty acids into adipose tissue leads to their redistribution to the liver. These results establish LRP1 as a novel integrator of adipogenic differentiation and fat storage signals.",
author = "J{\'e}rome Terrand and V{\'e}ronique Bruban and Li Zhou and Wanfeng Gong and Asmar, {Zeina El} and Petra May and Kai Zurhove and Philipp Haffner and Claude Philippe and Estelle Woldt and Matz, {Rachel L.} and C{\'e}line Gracia and Daniel Metzger and Johan Auwerx and Joachim Herz and Philippe Boucher",
year = "2009",
month = "1",
day = "2",
doi = "10.1074/jbc.M806538200",
language = "English (US)",
volume = "284",
pages = "381--388",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "1",

}

TY - JOUR

T1 - LRP1 controls intracellular cholesterol storage and fatty acid synthesis through modulation of wnt signaling

AU - Terrand, Jérome

AU - Bruban, Véronique

AU - Zhou, Li

AU - Gong, Wanfeng

AU - Asmar, Zeina El

AU - May, Petra

AU - Zurhove, Kai

AU - Haffner, Philipp

AU - Philippe, Claude

AU - Woldt, Estelle

AU - Matz, Rachel L.

AU - Gracia, Céline

AU - Metzger, Daniel

AU - Auwerx, Johan

AU - Herz, Joachim

AU - Boucher, Philippe

PY - 2009/1/2

Y1 - 2009/1/2

N2 - The low-density lipoprotein receptor-related protein LRP1 is a cell surface receptor with functions in diverse physiological pathways, including lipid metabolism. Here we show that LRP1- deficient fibroblasts accumulate high levels ofintracellular cholesterol and cholesteryl-ester when stimulated for adipocyte differentiation. We demonstrate that LRP1 stimulates a canonical Wnt5a signaling pathway that prevents cholesterol accumulation. Moreover, we show that LRP1 is required for lipolysis and stimulates fatty acid synthesis independently ofthe noradrener- gic pathway, through inhibition of GSK3β and its previously unknown target acetyl-CoA carboxylase (ACC). As a result of ACC inhibition, mature LRP1-deficient adipocytes of adult mice are hypotrophic, and lower uptake of fatty acids into adipose tissue leads to their redistribution to the liver. These results establish LRP1 as a novel integrator of adipogenic differentiation and fat storage signals.

AB - The low-density lipoprotein receptor-related protein LRP1 is a cell surface receptor with functions in diverse physiological pathways, including lipid metabolism. Here we show that LRP1- deficient fibroblasts accumulate high levels ofintracellular cholesterol and cholesteryl-ester when stimulated for adipocyte differentiation. We demonstrate that LRP1 stimulates a canonical Wnt5a signaling pathway that prevents cholesterol accumulation. Moreover, we show that LRP1 is required for lipolysis and stimulates fatty acid synthesis independently ofthe noradrener- gic pathway, through inhibition of GSK3β and its previously unknown target acetyl-CoA carboxylase (ACC). As a result of ACC inhibition, mature LRP1-deficient adipocytes of adult mice are hypotrophic, and lower uptake of fatty acids into adipose tissue leads to their redistribution to the liver. These results establish LRP1 as a novel integrator of adipogenic differentiation and fat storage signals.

UR - http://www.scopus.com/inward/record.url?scp=58649104220&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=58649104220&partnerID=8YFLogxK

U2 - 10.1074/jbc.M806538200

DO - 10.1074/jbc.M806538200

M3 - Article

VL - 284

SP - 381

EP - 388

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 1

ER -