Lipoprotein Receptor LRP1 Regulates Leptin Signaling and Energy Homeostasis in the Adult Central Nervous System
نویسندگان
چکیده
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.
منابع مشابه
Endothelial LRP1 regulates metabolic responses by acting as a co-activator of PPARγ
Low-density lipoprotein receptor-related protein 1 (LRP1) regulates lipid and glucose metabolism in liver and adipose tissue. It is also involved in central nervous system regulation of food intake and leptin signalling. Here we demonstrate that endothelial Lrp1 regulates systemic energy homeostasis. Mice with endothelial-specific Lrp1 deletion display improved glucose sensitivity and lipid pro...
متن کاملPropranolol Prevents Osteoporosis and up-regulates Leptin in Ovariectomized Rats
Osteoporosis is a systemic skeletal disease and there is a close relationship between the sympathetic nervous system (SNS) and bone metabolism. Leptin has been shown to regulate bone formation and bone resorption via the SNS. However, the effect of SNS on leptin signaling has not been clearly understood. In the present study, we studied the effect of propranolol on ovariectomy-induced osteoporo...
متن کاملPropranolol Prevents Osteoporosis and up-regulates Leptin in Ovariectomized Rats
Osteoporosis is a systemic skeletal disease and there is a close relationship between the sympathetic nervous system (SNS) and bone metabolism. Leptin has been shown to regulate bone formation and bone resorption via the SNS. However, the effect of SNS on leptin signaling has not been clearly understood. In the present study, we studied the effect of propranolol on ovariectomy-induced osteoporo...
متن کاملThe low-density lipoprotein receptor-related protein 1 and amyloid-β clearance in Alzheimer’s disease
Accumulation and aggregation of amyloid-β (Aβ) peptides in the brain trigger the development of progressive neurodegeneration and dementia associated with Alzheimer's disease (AD). Perturbation in Aβ clearance, rather than Aβ production, is likely the cause of sporadic, late-onset AD, which accounts for the majority of AD cases. Since cellular uptake and subsequent degradation constitute a majo...
متن کاملLRP1 regulates peroxisome biogenesis and cholesterol homeostasis in oligodendrocytes and is required for proper CNS myelin development and repair
Low-density lipoprotein receptor-related protein-1 (LRP1) is a large endocytic and signaling molecule broadly expressed by neurons and glia. In adult mice, global inducible (Lrp1flox/flox;CAG-CreER) or oligodendrocyte (OL)-lineage specific ablation (Lrp1flox/flox;Pdgfra-CreER) of Lrp1 attenuates repair of damaged white matter. In oligodendrocyte progenitor cells (OPCs), Lrp1 is required for cho...
متن کامل