AgRP Neurons Regulate Bone Mass
Copyright policy )AgRP Neurons Regulate Bone Mass
The hypothalamus has been implicated in skeletal metabolism. Whether hunger-promoting neurons of the arcuate nucleus impact the bone is not known. We generated multiple lines of mice to affect AgRP neuronal circuit integrity. We found that mice with Ucp2 gene deletion, in which AgRP neuronal function was impaired, were osteopenic. This phenotype was rescued by cell-selective reactivation of Ucp2 in AgRP neurons. When the AgRP circuitry was impaired by early postnatal deletion of AgRP neurons or by cell autonomous deletion of Sirt1 (AgRP-Sirt1(-/-)), mice also developed reduced bone mass. No impact of leptin receptor deletion in AgRP neurons was found on bone homeostasis. Suppression of sympathetic tone in AgRP-Sirt1(-/-) mice reversed osteopenia in transgenic animals. Taken together, these observations establish a significant regulatory role for AgRP neurons in skeletal bone metabolism independent of leptin action.
- Universität Augsburg Germany
- University Federico II of Naples Italy
- Anatomische Anstalt Germany
- Yale University United States
- Federal University of Rio de Janeiro Brazil
Genetics and Molecular Biology (all), Leptin, Male, QH301-705.5, Knockout, Hypothalamus, Agouti-Related Protein; Animals; Arcuate Nucleus of Hypothalamus; Bone Density; Bone Diseases, Metabolic; Femur; Gene Expression Regulation; Homeostasis; Hypothalamus; Ion Channels; Leptin; Male; Mice; Mice, Knockout; Mitochondrial Proteins; Neurons; Norepinephrine; Phenotype; Propranolol; Receptors, Adrenergic, beta; Receptors, Leptin; Signal Transduction; Sirtuin 1; Tibia; Uncoupling Protein 2; Biochemistry, Genetics and Molecular Biology (all), Biochemistry, Ion Channels, Mitochondrial Proteins, Mice, Norepinephrine, Sirtuin 1, Bone Density, Receptors, Receptors, Adrenergic, beta, Animals, Homeostasis, Uncoupling Protein 2, Agouti-Related Protein, Femur, Biology (General), Mice, Knockout, Neurons, ddc:610, Tibia, Arcuate Nucleus of Hypothalamus, Propranolol, Bone Diseases, Metabolic, Phenotype, Gene Expression Regulation, Adrenergic, beta, Metabolic, Bone Diseases, Signal Transduction
Genetics and Molecular Biology (all), Leptin, Male, QH301-705.5, Knockout, Hypothalamus, Agouti-Related Protein; Animals; Arcuate Nucleus of Hypothalamus; Bone Density; Bone Diseases, Metabolic; Femur; Gene Expression Regulation; Homeostasis; Hypothalamus; Ion Channels; Leptin; Male; Mice; Mice, Knockout; Mitochondrial Proteins; Neurons; Norepinephrine; Phenotype; Propranolol; Receptors, Adrenergic, beta; Receptors, Leptin; Signal Transduction; Sirtuin 1; Tibia; Uncoupling Protein 2; Biochemistry, Genetics and Molecular Biology (all), Biochemistry, Ion Channels, Mitochondrial Proteins, Mice, Norepinephrine, Sirtuin 1, Bone Density, Receptors, Receptors, Adrenergic, beta, Animals, Homeostasis, Uncoupling Protein 2, Agouti-Related Protein, Femur, Biology (General), Mice, Knockout, Neurons, ddc:610, Tibia, Arcuate Nucleus of Hypothalamus, Propranolol, Bone Diseases, Metabolic, Phenotype, Gene Expression Regulation, Adrenergic, beta, Metabolic, Bone Diseases, Signal Transduction
selected citations These citations are derived from selected sources.This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).45 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!