Lipoprotein receptor LRP1 regulates leptin signaling and energy homeostasis in the adult central nervous system

Qiang Liu, Juan Zhang, Celina Zerbinatti, Yan Zhan, Benedict J. Kolber, Joachim Herz, Louis J. Muglia, Guojun Bu

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Obesity is a growing epidemic characterized by excess fat storage in adipocytes. Although lipoprotein receptors play important roles in lipid uptake, their role in controlling food intake and obesity is not known. Here we show that the lipoprotein receptor LRP1 regulates leptin signaling and energy homeostasis. Conditional deletion of the Lrp1 gene in the brain resulted in an obese phenotype characterized by increased food intake, decreased energy consumption, and decreased leptin signaling. LRP1 directly binds to leptin and the leptin receptor complex and is required for leptin receptor phosphorylation and Stat3 activation. We further showed that deletion of the Lrp1 gene specifically in the hypothalamus by Cre lentivirus injection is sufficient to trigger accelerated weight gain. Together, our results demonstrate that the lipoprotein receptor LRP1, which is critical in lipid metabolism, also regulates food intake and energy homeostasis in the adult central nervous system.

Original languageEnglish (US)
Article numbere1000575
JournalPLoS Biology
Volume9
Issue number1
DOIs
StatePublished - 2011

Fingerprint

Lipoprotein Receptors
Neurology
Leptin
leptin
lipoproteins
central nervous system
Leptin Receptors
food intake
homeostasis
Homeostasis
Central Nervous System
gene deletion
Eating
Gene Deletion
receptors
energy
obesity
Obesity
Genes
Lentivirus

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)

Cite this

Lipoprotein receptor LRP1 regulates leptin signaling and energy homeostasis in the adult central nervous system. / Liu, Qiang; Zhang, Juan; Zerbinatti, Celina; Zhan, Yan; Kolber, Benedict J.; Herz, Joachim; Muglia, Louis J.; Bu, Guojun.

In: PLoS Biology, Vol. 9, No. 1, e1000575, 2011.

Research output: Contribution to journalArticle

Liu, Qiang ; Zhang, Juan ; Zerbinatti, Celina ; Zhan, Yan ; Kolber, Benedict J. ; Herz, Joachim ; Muglia, Louis J. ; Bu, Guojun. / Lipoprotein receptor LRP1 regulates leptin signaling and energy homeostasis in the adult central nervous system. In: PLoS Biology. 2011 ; Vol. 9, No. 1.
@article{afc120d1a2c44f93b6cc11cb106cce74,
title = "Lipoprotein receptor LRP1 regulates leptin signaling and energy homeostasis in the adult central nervous system",
abstract = "Obesity is a growing epidemic characterized by excess fat storage in adipocytes. Although lipoprotein receptors play important roles in lipid uptake, their role in controlling food intake and obesity is not known. Here we show that the lipoprotein receptor LRP1 regulates leptin signaling and energy homeostasis. Conditional deletion of the Lrp1 gene in the brain resulted in an obese phenotype characterized by increased food intake, decreased energy consumption, and decreased leptin signaling. LRP1 directly binds to leptin and the leptin receptor complex and is required for leptin receptor phosphorylation and Stat3 activation. We further showed that deletion of the Lrp1 gene specifically in the hypothalamus by Cre lentivirus injection is sufficient to trigger accelerated weight gain. Together, our results demonstrate that the lipoprotein receptor LRP1, which is critical in lipid metabolism, also regulates food intake and energy homeostasis in the adult central nervous system.",
author = "Qiang Liu and Juan Zhang and Celina Zerbinatti and Yan Zhan and Kolber, {Benedict J.} and Joachim Herz and Muglia, {Louis J.} and Guojun Bu",
year = "2011",
doi = "10.1371/journal.pbio.1000575",
language = "English (US)",
volume = "9",
journal = "PLoS Biology",
issn = "1544-9173",
publisher = "Public Library of Science",
number = "1",

}

TY - JOUR

T1 - Lipoprotein receptor LRP1 regulates leptin signaling and energy homeostasis in the adult central nervous system

AU - Liu, Qiang

AU - Zhang, Juan

AU - Zerbinatti, Celina

AU - Zhan, Yan

AU - Kolber, Benedict J.

AU - Herz, Joachim

AU - Muglia, Louis J.

AU - Bu, Guojun

PY - 2011

Y1 - 2011

N2 - Obesity is a growing epidemic characterized by excess fat storage in adipocytes. Although lipoprotein receptors play important roles in lipid uptake, their role in controlling food intake and obesity is not known. Here we show that the lipoprotein receptor LRP1 regulates leptin signaling and energy homeostasis. Conditional deletion of the Lrp1 gene in the brain resulted in an obese phenotype characterized by increased food intake, decreased energy consumption, and decreased leptin signaling. LRP1 directly binds to leptin and the leptin receptor complex and is required for leptin receptor phosphorylation and Stat3 activation. We further showed that deletion of the Lrp1 gene specifically in the hypothalamus by Cre lentivirus injection is sufficient to trigger accelerated weight gain. Together, our results demonstrate that the lipoprotein receptor LRP1, which is critical in lipid metabolism, also regulates food intake and energy homeostasis in the adult central nervous system.

AB - Obesity is a growing epidemic characterized by excess fat storage in adipocytes. Although lipoprotein receptors play important roles in lipid uptake, their role in controlling food intake and obesity is not known. Here we show that the lipoprotein receptor LRP1 regulates leptin signaling and energy homeostasis. Conditional deletion of the Lrp1 gene in the brain resulted in an obese phenotype characterized by increased food intake, decreased energy consumption, and decreased leptin signaling. LRP1 directly binds to leptin and the leptin receptor complex and is required for leptin receptor phosphorylation and Stat3 activation. We further showed that deletion of the Lrp1 gene specifically in the hypothalamus by Cre lentivirus injection is sufficient to trigger accelerated weight gain. Together, our results demonstrate that the lipoprotein receptor LRP1, which is critical in lipid metabolism, also regulates food intake and energy homeostasis in the adult central nervous system.

UR - http://www.scopus.com/inward/record.url?scp=79851497711&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79851497711&partnerID=8YFLogxK

U2 - 10.1371/journal.pbio.1000575

DO - 10.1371/journal.pbio.1000575

M3 - Article

VL - 9

JO - PLoS Biology

JF - PLoS Biology

SN - 1544-9173

IS - 1

M1 - e1000575

ER -