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

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.

Pubmed ID: 21264353

Authors

  • Liu Q
  • Zhang J
  • Zerbinatti C
  • Zhan Y
  • Kolber BJ
  • Herz J
  • Muglia LJ
  • Bu G

Journal

PLoS biology

Publication Data

January 25, 2011

Associated Grants

  • Agency: NIDDK NIH HHS, Id: 5P60DK020579
  • Agency: NHLBI NIH HHS, Id: HL20948
  • Agency: NHLBI NIH HHS, Id: HL63762
  • Agency: NIA NIH HHS, Id: P01 AG030128
  • Agency: NIA NIH HHS, Id: P01 AG03012801
  • Agency: NIA NIH HHS, Id: R01 AG02792405
  • Agency: NIA NIH HHS, Id: R01 AG035355
  • Agency: NHLBI NIH HHS, Id: R37 HL063762

Mesh Terms

  • Agouti-Related Protein
  • Animals
  • Appetite Regulation
  • Brain
  • Cell Line
  • Energy Metabolism
  • Female
  • Glucose Intolerance
  • Homeostasis
  • Hyperlipidemias
  • Hypothalamus
  • Insulin Resistance
  • Leptin
  • Lipid Metabolism
  • Male
  • Mice
  • Mice, Knockout
  • Neuropeptide Y
  • Obesity
  • Receptors, LDL
  • Tumor Suppressor Proteins
  • Up-Regulation