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

PLoS biology | 2011

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 RIS Download

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Associated grants

  • Agency: NIA NIH HHS, United States
    Id: R01 AG035355
  • Agency: NHLBI NIH HHS, United States
    Id: HL20948
  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL063762
  • Agency: NIA NIH HHS, United States
    Id: P01 AG03012801
  • Agency: NIA NIH HHS, United States
    Id: P01 AG030128
  • Agency: NIA NIH HHS, United States
    Id: R01 AG02792405
  • Agency: NIDDK NIH HHS, United States
    Id: P60 DK020579
  • Agency: NHLBI NIH HHS, United States
    Id: R37 HL063762
  • Agency: NIDDK NIH HHS, United States
    Id: 5P60DK020579
  • Agency: NHLBI NIH HHS, United States
    Id: P01 HL020948
  • Agency: NHLBI NIH HHS, United States
    Id: HL63762

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