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.
Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, United States of America.
Qiang
Q
Liu
Juan
J
Zhang
Celina
C
Zerbinatti
Yan
Y
Zhan
Benedict J
BJ
Kolber
Joachim
J
Herz
Louis J
LJ
Muglia
Guojun
G
Bu
D054369:Agouti-Related Protein / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D001069:Appetite Regulation; D001921:Brain / Q000378:metabolism*; D002460:Cell Line; D004734:Energy Metabolism; D005260:Female; D018149:Glucose Intolerance / Q000235:genetics / Q000378:metabolism; D006706:Homeostasis; D006949:Hyperlipidemias / Q000235:genetics / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism; D007333:Insulin Resistance; D020738:Leptin / Q000502:physiology*; D050356:Lipid Metabolism / Q000187:drug effects; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009478:Neuropeptide Y / Q000096:biosynthesis / Q000235:genetics; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D011973:Receptors, LDL / Q000172:deficiency* / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000172:deficiency* / Q000235:genetics; D015854:Up-Regulation
D054369:Agouti-Related Protein; D020738:Leptin; D026503:Low Density Lipoprotein Receptor-Related Protein-1; C486645:Lrp1 protein, mouse; D009478:Neuropeptide Y; D011973:Receptors, LDL; D025521:Tumor Suppressor Proteins
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